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| ID | Type | Description | Link |
|---|---|---|---|
| 1U01DE024169-01 | U.S. NIH Grant/Contract | View source | |
| 14-067-E | Other Identifier | NIDCR Protocol Number |
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| Name | Class |
|---|---|
| University of Florida | OTHER |
| Rho, Inc. | INDUSTRY |
| National Institutes of Health (NIH) | NIH |
| National Institute of Dental and Craniofacial Research (NIDCR) |
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Purpose:
Primary: To evaluate the efficacy of extended-release (ER) propranolol compared to placebo in the reduction of a pain index in patients with temporomandibular disorder (TMD).
Secondary: To determine if extended-release propranolol efficacy varies according to participants' catechol-O-methyltransferase (COMT) genetic polymorphisms and to investigate the efficacy of extended-release propranolol compared with placebo using secondary endpoints.
Exploratory: To investigate whether the efficacy of extended-release propranolol in the reduction of the pain index varies according to participants' polymorphisms in 3 other genetic regions and according to various phenotypic characteristics.
Participants:
200 patients with chronic TMD will be randomly assigned, in a 1:1 parallel, double-blind fashion, to receive either extended-release propranolol or placebo at one of three study sites: University of North Carolina-Chapel Hill School of Dentistry; University of Florida-Gainesville College of Dentistry; and the State University of New York at Buffalo School of Dental Medicine.
Procedures (methods):
Randomization will be to either propranolol or placebo. The 10-week study treatment period is divided into: 1 week of drug titration, 8 weeks of drug maintenance, and 1 week of drug tapering. The titration and tapering doses are 60 mg (capsules) once per day orally; the maintenance dose is 60 mg twice per day orally. Participants will attend 6 clinic visits over 12-15 weeks as follows: screening and baseline visit (Visit [V] 0, 7-21 days prior to V1); randomization and start of treatment (titration) (V1, study day 0); maintenance visit 2 (V2, 1 week post-randomization, study day 7+3); maintenance visit 3 (V3, 5 weeks post-randomization, study day 35 +/- 7); tapering visit (V4, 9 weeks post-randomization, study day 63 +/- 7); and tapering visit 5 (V5, 11 weeks post-randomization and 1 week after drug tapering ends, study day 77 +/- 7). Depending on the visit, procedures will include: reviews of medical history, weekly alcohol consumption, concomitant therapies and medications, adverse events, compliance, and eligibility; administration/review of questionnaires; blood draw; pregnancy test in women of childbearing potential; and dispensing of study drug.
"Temporomandibular disorder" (TMD) encompasses all musculoskeletal disorders of the masticatory system and includes myalgia, arthralgia, temporomandibular joint (TMJ) disc displacements, and TMJ degenerative joint diseases. The prevalence of TMD ranges from 6% to 12% in the general population, with muscle dysfunction the most prevalent TMD diagnostic group. TMD is associated with substantial disability and suffering and negatively impacts quality of life. Jaw pain is the most common symptom that compels treatment seeking. In addition to facial pain, TMD patients frequently report comorbid pain conditions such as headache, low back pain, and fibromyalgia. New approaches to TMD therapy are urgently needed to improve clinical outcomes and reduce economic impact of this disorder.
There is currently no FDA-approved product labeled specifically to manage/treat TMD; however, classes of drugs are used to relieve TMD-associated pain, such as non-steroidal anti-inflammatory drugs (NSAIDs), anti-inflammatory drugs, corticosteroids, benzodiazepines, sedative hypnotics, muscle relaxants, opioids, antidepressants, and anticonvulsants - although evidence to establish their efficacy and safety in this population is scarce. Practitioners' justification for their use may be based on poorly controlled clinical trials or clinical trials in other pain disorders such as acute postsurgical dental pain, arthritic pain, chronic lower back pain, and neuropathic pain. Thus, there is a need for controlled clinical trials to better understand the physiological mechanisms responsible for TMD symptoms.
Evidence suggests that enhanced β-adrenergic drive contributes to the pathogenesis of TMD and other complex persistent pain conditions. For example, individuals with myofascial pain conditions have elevated catecholamine levels and augmented sympathetic responses to stressors. While increased β-adrenergic drive appears to heighten pain, β-adrenergic antagonists can reduce clinical pain and/or nociceptive sensitivity. A recent study of a single infusion of propranolol in TMD and fibromyalgia patients revealed short-term improvement in clinical pain ratings. The antagonist pindolol was similarly efficacious in alleviating cardinal symptoms of fibromyalgia pain. In addition, intramuscular injections of low-dose propranolol in rats reduced inflammatory pain associated with carrageen-induced inflammation of the gastrocnemius muscle.
The study hypothesis is that therapy with the nonselective β-adrenergic receptor antagonist propranolol extended-release capsules (FDA approved to treat many cardiac conditions, tremor, migraine, and pheochromocytoma) will provide efficacious and safe treatment for painful TMD. It has well-studied pharmacodynamic, pharmacokinetic, and side-effect profiles. Peak blood level occurs at approximately 6 hrs, and the plasma half-life is approximately 10 hrs. The primary objective is to investigate the efficacy of propranolol compared with placebo over 9 weeks to reduce pain in patients with TMD. Secondary objectives are to: investigate by treatment group whether reduction in pain varies according to polymorphisms in the COMT gene coding region; and investigate the effect of propranolol compared with placebo to affect pain sensitivity, physical and emotional function, adverse effects, and use of rescue medications. Exploratory objectives are to: investigate gene-by-treatment group interaction to determine the effect of propranolol on reduction in the pain index according to polymorphisms in the COMT, beta-2 adrenergic receptor (ADRβ2), and beta-3 adrenergic receptor (ADRβ3) genetic coding regions.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Propranolol ER | Active Comparator | Propranolol hydrochloride extended release (ER) capsules; 60 mg (Visit 1 and Visit 4); 120 mg (Visit 2 and Visit 3) given orally as: 60 mg once/day (Visit 1 and Visit 4) and 60 mg twice/day (Visit 2 and Visit 3). |
|
| Placebo | Placebo Comparator | Capsules, identical in appearance to active comparator (propranolol), to be administered orally in exactly the same manner as propranolol at Visit 1 (once/day), Visit 2 (twice/day), Visit 3 (twice/day), and Visit 4 (once/day). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Propranolol ER | Drug | Capsules given orally according to schedule at Visit 1, Visit 2, Visit 3, and Visit 4. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in the Weekly Mean Pain Index After 9 Weeks of Treatment | Weekly mean pain index computed as the arithmetic mean of daily pain index values during the week prior to randomization and prior to each study visit. Daily pain index is computed as pain intensity (0-100 numeric rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable") multiplied by pain duration (0-100 percentage scale where percent = "percent of waking day you had facial pain") as reported in the Daily Symptom Diary and divided by 100. The pain index range is from 0 to 100. A higher score means a worse outcome. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in the Weekly Mean Pain Intensity After 9 Weeks of Treatment | Weekly mean pain intensity computed as the arithmetic mean of daily pain intensity values during the week prior to randomization and prior to each study visit. Daily pain intensity is measured on 0-100 numeric rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable") as reported in the Daily Symptom Diary. A higher score means a worse outcome. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in the Weekly Mean Pain Index After 9 Weeks of Treatment Stratified Per Number of COMT LPS Haplotypes | Weekly mean pain index computed as the arithmetic mean of daily pain index values during the week prior to randomization and prior to each study visit. Daily pain index is computed as pain intensity (0-100 numeric rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable") multiplied by pain duration (0-100 percentage scale where percent = "percent of waking day you had facial pain") as reported in the Daily Symptom Diary, divided by 100. The pain index range is from 0 to 100. A higher score means a worse outcome. The pain index was stratified per number of catechol-O-methyltransferase (COMT) Low Pain Sensitive (LPS) haplotypes. |
Inclusion:
Exclusion:
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| Name | Affiliation | Role |
|---|---|---|
| Inna E. Tchivileva, MD | University of North Carolina, Chapel Hill | Principal Investigator |
| Roger B. Fillingim, PhD | University of Florida-Gainesville College of Dentistry | Principal Investigator |
| Richard Ohrbach, DDS, PhD | University at Buffalo School of Dental Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Florida-Gainesville College of Dentistry | Gainesville | Florida | 32610-0404 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20216107 | Background | Tchivileva IE, Lim PF, Smith SB, Slade GD, Diatchenko L, McLean SA, Maixner W. Effect of catechol-O-methyltransferase polymorphism on response to propranolol therapy in chronic musculoskeletal pain: a randomized, double-blind, placebo-controlled, crossover pilot study. Pharmacogenet Genomics. 2010 Apr;20(4):239-48. doi: 10.1097/FPC.0b013e328337f9ab. | |
| 12739038 | Background | Gursoy S, Erdal E, Herken H, Madenci E, Alasehirli B, Erdal N. Significance of catechol-O-methyltransferase gene polymorphism in fibromyalgia syndrome. Rheumatol Int. 2003 May;23(3):104-7. doi: 10.1007/s00296-002-0260-5. Epub 2002 Oct 22. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Propranolol ER | Propranolol hydrochloride extended release (ER) capsules; 60 mg (Visit 1 and Visit 4); 120 mg (Visit 2 and Visit 3) given orally as: 60 mg once/day (Visit 1 and Visit 4) and 60 mg twice/day (Visit 2 and Visit 3). Propranolol ER: Capsules given orally according to schedule at Visit 1, Visit 2, Visit 3, and Visit 4. |
| FG001 | Placebo | Capsules, identical in appearance to active comparator (propranolol), to be administered orally in exactly the same manner as propranolol at Visit 1 (once/day), Visit 2 (twice/day), Visit 3 (twice/day), and Visit 4 (once/day). Placebo: Gelatin capsules with a microcrystalline cellulose filler manufactured to mimic propranolol ER 60 mg capsules |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
All participants who received at least one dose of treatment and provided at least one post-baseline data point (N=199). No data were available for one randomized participant in the placebo arm.
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| ID | Title | Description |
|---|---|---|
| BG000 | Propranolol ER | Propranolol hydrochloride extended release (ER) capsules; 60 mg (Visit 1 and Visit 4); 120 mg (Visit 2 and Visit 3) given orally as: 60 mg once/day (Visit 1 and Visit 4) and 60 mg twice/day (Visit 2 and Visit 3). Propranolol ER: Capsules given orally according to schedule at Visit 1, Visit 2, Visit 3, and Visit 4. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in the Weekly Mean Pain Index After 9 Weeks of Treatment | Weekly mean pain index computed as the arithmetic mean of daily pain index values during the week prior to randomization and prior to each study visit. Daily pain index is computed as pain intensity (0-100 numeric rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable") multiplied by pain duration (0-100 percentage scale where percent = "percent of waking day you had facial pain") as reported in the Daily Symptom Diary and divided by 100. The pain index range is from 0 to 100. A higher score means a worse outcome. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
|
From obtaining informed consent until 7 (for nonserious AEs) or 30 days (for SAEs) after the last day of study participation.
8 AEs commonly reported with use of propranolol were solicited by a questionnaire administered at each study visit. All the rest of the AEs were solicited through the open-question inquiries at each study visit. Data are reported for AEs that occurred in the safety sample which includes all randomized participants who received at least one dose of study medication. Participants are analyzed according to the medication they actually received, regardless of their randomized assignment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Propranolol ER | Propranolol hydrochloride extended release (ER) capsules; 60 mg (Visit 1 and Visit 4); 120 mg (Visit 2 and Visit 3) given orally as: 60 mg once/day (Visit 1 and Visit 4) and 60 mg twice/day (Visit 2 and Visit 3). Propranolol ER: Capsules given orally according to schedule at Visit 1, Visit 2, Visit 3, and Visit 4. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Non-systematic Assessment | Occurred in a participant with metastatic breast cancer |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Inna E. Tchivileva | University of North Carolina at Chapel Hill | 1 919 537 3291 | inna_tchivileva@unc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 12, 2018 | Mar 27, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 21, 2018 | Mar 27, 2019 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D013705 | Temporomandibular Joint Disorders |
| ID | Term |
|---|---|
| D017271 | Craniomandibular Disorders |
| D008336 | Mandibular Diseases |
| D007571 | Jaw Diseases |
| D009140 | Musculoskeletal Diseases |
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| ID | Term |
|---|---|
| D011433 | Propranolol |
| D000073893 | Sugars |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
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| NIH |
| State University of New York at Buffalo | OTHER |
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| Placebo | Drug | Gelatin capsules with a microcrystalline cellulose filler manufactured to mimic propranolol ER 60 mg capsules |
|
|
| Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in the Weekly Mean Pain Duration After 9 Weeks of Treatment | Weekly mean pain duration computed as the arithmetic mean of daily pain duration values during the week prior to randomization and prior to each study visit. Daily pain duration is measured on 0-100 percentage scale where percent = "percent of waking day you had facial pain" as reported in the Daily Symptom Diary. A higher score means a worse outcome. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in the SF-McGill Pain Questionnaire Affective Component After 9 Weeks of Treatment | The SF-McGill Pain Questionnaire contains 4 affective descriptors rated on a 0-3 scale where 0 = "none," 1 = "mild," 2 = "moderate," and 3 = "severe." The item scores are summed to yield a total score ranging from 0 to 12. A higher score means a worse outcome. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in the SF-McGill Pain Questionnaire Sensory Component After 9 Weeks of Treatment | The SF-McGill Pain Questionnaire contains 11 sensory descriptors rated on a 0-3 scale where 0 = "none," 1 = "mild," 2 = "moderate," and 3 = "severe." The item scores are summed to yield a total score ranging from 0 to 33. A higher score means a worse outcome. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in the SF-McGill Pain Questionnaire Present Facial Pain Intensity After 9 Weeks of Treatment | Self-reported present intensity of facial pain at the moment of assessment scored on a descriptive scale where 1 = "no pain' and 6 = "excruciating pain." A higher score means worse outcome. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in the SF-McGill Pain Questionnaire Weekly Average Facial Pain Intensity After 9 Weeks of Treatment | Self-reported average facial pain intensity for the last week scored on 0-100 numerical rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable". A higher score means a worse outcome. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in the SF-McGill Pain Questionnaire Weekly Average Facial Pain Duration After 9 Weeks of Treatment | Self-reported average facial pain duration for the last week scored on 0-100 percentage scale where percent = "percent of waking day you had facial pain". A higher score means a worse outcome. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in the SF-McGill Pain Questionnaire Weekly Fatigue After 9 Weeks of Treatment | Self-reported average fatigue for the last week scored on 0-100 numerical rating scale where 0 = "no fatigue" and 100 = "the greatest imaginable." A higher score means a worse outcome. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Number of Participants Stratified Per Graded Chronic Pain Scale (GCPS) Grade After 9 Weeks of Treatment | Individuals were classified into 6 chronic pain grades: 0 = no pain; I = low pain intensity and low pain-related disability; IIa = high pain intensity and low pain-related disability; IIb = high pain intensity and high activity interference; III = moderate pain-related disability; and IV = severe pain-related disability. For analyses, this variable was dichotomized: grades 0-IIa were combined in one category and all higher grades in another. A higher grade means a worse outcome. | Visit 4 (study day 63 +/-7) |
| Change in the Jaw Functional Limitation Scale (JFLS) Global Score After 9 Weeks of Treatment | The JFLS contains 20 items that measure limitations across mastication, vertical jaw mobility, and verbal/emotional expression rated on a 0-10 scale where 0 = "no limitation" and 10 = "severe limitation." The Global Score is computed as the mean response for all items and ranges from 0 to 10. A higher score means a worse outcome. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in the Headache Impact Test (HIT-6) Global Score After 9 Weeks of Treatment | The HIT-6 contains 6 items and assesses headache-related disability by the frequency of daily activity limitations ranging from "never" to "always." The 6 item scores are summed to yield a global score ranging from 36 to 78. A higher score means a worse outcome. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in the Pittsburgh Sleep Quality Index (PSQI) Global Score After 9 Weeks of Treatment | The PSQI has 19 items grouped into 7 component scores, each weighted equally on a 0-3 scale, The 7 component scores are summed to yield a global PSQI score, which has a range of 0-21. A higher score means a worse outcome. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Number of Participants Stratified Per Dichotomized Score From the Patient Global Impression of Change (PGIC) Scale After 9 Weeks of Treatment | The PGIC scale assesses patient overall change in the severity of illness following treatment. Participants rate how they feel now compared with how they felt before receiving study drug on a 7-point scale where 0 = "No change or condition has got worse" and 6 = "A great deal better." A higher score means a better outcome. For analyses, this variable was dichotomized: scores from 0 to 3 were combined in one category of "No" (no significant improvement) and scores from 4 to 6 were combined in another category of "Yes" (significant improvement with the study treatment). | Visit 4 (study day 63 +/-7) |
| Change in the Perceived Stress Scale (PSS) Global Score After 9 Weeks of Treatment | The PSS assesses the frequency of 14 sources of stress on a scale from 0 = "never" to 4 = "very often." The item scores are summed to yield a global score ranging from 0 to 56. A higher score means a worse outcome. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in the Hospital Anxiety and Depression Scale (HADS) Depression Score After 9 Weeks of Treatment | The HADS is a 14-item assessment of anxiety (7 items) and depression (7 items) using the relative frequency of symptoms over the past week, rated on a 4-point scale ranging from 0 = "not at all" to 3 = "very often indeed". Responses are summed to provide separate scores for anxiety and depression with a range from 0 to 21. A higher score means a worse outcome. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in the Hospital Anxiety and Depression Scale (HADS) Anxiety Score After 9 Weeks of Treatment | The HADS is a 14-item assessment of anxiety (7 items) and depression (7 items) using the relative frequency of symptoms over the past week, rated on a 4-point scale ranging from 0 = "not at all" to 3 = "very often indeed". Responses are summed to provide separate scores for anxiety and depression with a range from 0 to 21. A higher score means a worse outcome. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in the Symptom Checklist 90-Revised (SCL-90R) Somatization Scale Score After 9 Weeks of Treatment | The SCL-90R Somatization Scale is a 12-item assessment of somatic symptom distress over the past 7 days rated from 0 = "not at all" to 4 = "extremely." The scale score is computed as the mean for all items. The score range is from 0 to 4. A higher score means a worse outcome. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in the SF-12 Health Survey v2 (SF-12v2) Physical Component Summary (PCS) After 9 Weeks of Treatment | The SF-12v2 contains 7 questions assessing 8 domains of functioning and well-being rated from: "excellent" to "poor" (for general health); "yes, limited a lot" to "no, not limited at all" (for functional level); and "all of the time" to "none of the time" (for emotional state). These 8 domains can be further summarized into a physical component summary (PCS) and a mental component summary (MCS). summary (MCS). The range for each component is 0-100 and a higher score means a better outcome. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in the SF-12 Health Survey v2 (SF-12v2) Mental Component Summary (MCS) After 9 Weeks of Treatment | The SF-12v2 contains 7 questions assessing 8 domains of functioning and well-being rated from: "excellent" to "poor" (for general health); "yes, limited a lot" to "no, not limited at all" (for functional level); and "all of the time" to "none of the time" (for emotional state). These 8 domains can be further summarized into a physical component summary (PCS) and a mental component summary (MCS). The range for each component is 0-100 and a higher score means a better outcome. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in Thermal Pain Threshold After 9 Weeks of Treatment | Temperature values, measured in degrees Celsius, from 4 examiner-applied contact heat stimuli will be averaged to measure the experimental thermal pain threshold (temperature at which pain is first perceived). The range was 32-50 degrees Celsius and a higher value means a better outcome. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in Thermal Pain Tolerance After 9 Weeks of Treatment | Temperature values, measured in degrees Celsius, from 4 examiner-applied contact heat stimuli will be averaged to measure the experimental thermal pain tolerance (temperature at which pain can no longer be tolerated). The range was 32-50 degrees Celsius and a higher value means a better outcome. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in Pressure Pain Threshold at Temporalis Muscle After 9 Weeks of Treatment | Pressure values, measured in kilopascals (kPa), from up to 5 experimental pressure stimuli, bilaterally applied to the area of temporalis muscle, are averaged to obtain a single pressure pain threshold value per anatomical site. The range is 0-500 kPa and a higher value means a better outcome. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in Pressure Pain Threshold at Masseter Muscle After 9 Weeks of Treatment | Pressure values, measured in kilopascals, from up to 5 experimental pressure stimuli, bilaterally applied to the area of masseter muscle, will be averaged to obtain a single pressure pain threshold value per anatomical site. | Visit 1 (study day 0) and Visit 4 (study day 63 +/- 7) |
| Change in Pressure Pain Threshold at Temporomandibular Joint After 9 Weeks of Treatment | Pressure values, measured in kilopascals, from up to 5 experimental pressure stimuli, bilaterally applied to the area of temporomandibular joint, will be averaged to obtain a single pressure pain threshold value per anatomical site. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in Pressure Pain Threshold at Trapezius Muscle After 9 Weeks of Treatment | Pressure values, measured in kilopascals, from up to 5 experimental pressure stimuli, bilaterally applied to the area of trapezius muscle, will be averaged to obtain a single pressure pain threshold value per anatomical site. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in Pressure Pain Threshold at Lateral Epicondyle After 9 Weeks of Treatment | Pressure values, measured in kilopascals, from up to 5 experimental pressure stimuli, bilaterally applied to the area of lateral epicondyle, will be averaged to obtain a single pressure pain threshold value per anatomical site. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in Pain-free Jaw Opening After 9 Weeks of Treatment | Measured at TMD exam. A higher value means a better outcome. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in Maximum Unassisted Jaw Opening After 9 Weeks of Treatment | Measured at TMD exam. A higher value means a better outcome. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in Maximum Assisted Jaw Opening After 9 Weeks of Treatment | Measured at TMD exam. A higher value means a better outcome. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in Systolic Blood Pressure After 9 Weeks of Treatment | Average of 3 repeated measures taken with a 2-minute interval. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in Diastolic Blood Pressure After 9 Weeks of Treatment | Average of 3 repeated measures taken with a 2-minute interval. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in Heart Rate After 9 Weeks of Treatment | Average of 3 repeated measures taken with a 2-minute interval. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| Change in the Weekly Mean Pain Index After 9 Weeks of Treatment Stratified Per Number of COMT Valine Alleles at rs4680 | Weekly mean pain index computed as the arithmetic mean of daily pain index values during the week prior to randomization and prior to each study visit. Daily pain index is computed as pain intensity (0-100 numeric rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable") multiplied by pain duration (0-100 percentage scale where percent = "percent of waking day you had facial pain") as reported in the Daily Symptom Diary, divided by 100. The pain index range is from 0 to 100. A higher score means a worse outcome. The pain index was stratified per number of catechol-O-methyltransferase (COMT) valine alleles at single nucleotide polymorphism (SNP) rs4680. | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
| University at Buffalo School of Dental Medicine |
| Buffalo |
| New York |
| 14214 |
| United States |
| University of North Carolina at Chapel Hill School of Dentistry | Chapel Hill | North Carolina | 27599 | United States |
| 15537663 | Background | Diatchenko L, Slade GD, Nackley AG, Bhalang K, Sigurdsson A, Belfer I, Goldman D, Xu K, Shabalina SA, Shagin D, Max MB, Makarov SS, Maixner W. Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet. 2005 Jan 1;14(1):135-43. doi: 10.1093/hmg/ddi013. Epub 2004 Nov 10. |
| 34022805 | Derived | Tchivileva IE, Ohrbach R, Fillingim RB, Lin FC, Lim PF, Arbes SJ Jr, Slade GD. Clinical, psychological, and sensory characteristics associated with headache attributed to temporomandibular disorder in people with chronic myogenous temporomandibular disorder and primary headaches. J Headache Pain. 2021 May 22;22(1):42. doi: 10.1186/s10194-021-01255-1. |
| 33560875 | Derived | Tchivileva IE, Ohrbach R, Fillingim RB, Lim PF, Giosia MD, Ribeiro-Dasilva M, Campbell JH, Hadgraft H, Willis J, Arbes SJ Jr, Slade GD. Effect of comorbid migraine on propranolol efficacy for painful TMD in a randomized controlled trial. Cephalalgia. 2021 Jun;41(7):839-850. doi: 10.1177/0333102421989268. Epub 2021 Feb 9. |
| 33030089 | Derived | Slade GD, Fillingim RB, Ohrbach R, Hadgraft H, Willis J, Arbes SJ Jr, Tchivileva IE. COMT Genotype and Efficacy of Propranolol for TMD Pain: A Randomized Trial. J Dent Res. 2021 Feb;100(2):163-170. doi: 10.1177/0022034520962733. Epub 2020 Oct 8. |
| 32701836 | Derived | Tchivileva IE, Hadgraft H, Lim PF, Di Giosia M, Ribeiro-Dasilva M, Campbell JH, Willis J, James R, Herman-Giddens M, Fillingim RB, Ohrbach R, Arbes SJ Jr, Slade GD. Efficacy and safety of propranolol for treatment of temporomandibular disorder pain: a randomized, placebo-controlled clinical trial. Pain. 2020 Aug;161(8):1755-1767. doi: 10.1097/j.pain.0000000000001882. |
| 32297945 | Derived | Sanders AE, Slade GD, Fillingim RB, Ohrbach R, Arbes SJ Jr, Tchivileva IE. Effect of Treatment Expectation on Placebo Response and Analgesic Efficacy: A Secondary Aim in a Randomized Clinical Trial. JAMA Netw Open. 2020 Apr 1;3(4):e202907. doi: 10.1001/jamanetworkopen.2020.2907. |
| Placebo |
Capsules, identical in appearance to active comparator (propranolol), to be administered orally in exactly the same manner as propranolol at Visit 1 (once/day), Visit 2 (twice/day), Visit 3 (twice/day), and Visit 4 (once/day). Placebo: Gelatin capsules with a microcrystalline cellulose filler manufactured to mimic propranolol ER 60 mg capsules |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Weekly Mean Pain Intensity | Weekly mean pain intensity computed as the arithmetic mean of daily pain intensity values during the week prior to randomization. Daily pain intensity is measured on 0-100 numeric rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable") as reported in the Daily Symptom Diary. A higher score means a worse outcome. | Mean | Standard Deviation | units on a scale |
|
| Weekly Mean Pain Duration | Weekly mean pain duration computed as the arithmetic mean of daily pain duration values during the week prior to randomization. Daily pain duration is measured on 0-100 percentage scale where percent = "percent of waking day you had facial pain" as reported in the Daily Symptom Diary. A higher score means a worse outcome. | Mean | Standard Deviation | units on a scale |
|
| Weekly Mean Pain Index | Weekly mean pain index computed as the arithmetic mean of daily pain index values during the week prior to randomization. Daily pain index is computed as pain intensity (0-100 numeric rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable") multiplied by pain duration (0-100 percentage scale where percent = "percent of waking day you had facial pain") as reported in the Daily Symptom Diary, divided by 100. The pain index range is from 0 to 100. A higher score means a worse outcome. | Mean | Standard Deviation | units on a scale |
|
| The SF-McGill Pain Questionnaire Affective Component | The SF-McGill Pain Questionnaire contains 4 affective descriptors rated on a 0-3 scale where 0 = "none," 1 = "mild," 2 = "moderate," and 3 = "severe."The item scores are summed to yield a total score with a range from 0 to 12. A higher score means a worse outcome. | Mean | Standard Deviation | units on a scale |
|
| The SF-McGill Pain Questionnaire Sensory Component | The SF-McGill Pain Questionnaire contains 11 sensory descriptors rated on a 0-3 scale where 0 = "none," 1 = "mild," 2 = "moderate," and 3 = "severe."The item scores are summed to yield a total score with a range form 0 to 33. A higher score means a worse outcome. | Mean | Standard Deviation | units on a scale |
|
| The SF-McGill Pain Questionnaire Present Facial Pain Intensity | Self-reported present intensity of facial pain at the moment of assessment scored on a descriptive scale where 1 = "no pain' and 6 = "excruciating pain." A higher score means worse outcome. | Mean | Standard Deviation | units on a scale |
|
| The SF-McGill Pain Questionnaire Weekly Average Facial Pain Intensity | Self-reported average facial pain intensity for the last week scored on 0-100 numerical rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable". A higher score means a worse outcome. | Mean | Standard Deviation | units on a scale |
|
| The SF-McGill Pain Questionnaire Weekly Average Facial Pain Duration | Self-reported average facial pain duration for the last week scored on 0-100 percentage scale where percent = "percent of waking day you had facial pain." A higher score means a worse outcome. | Mean | Standard Deviation | units on a scale |
|
| The SF-McGill Pain Questionnaire Weekly Fatigue | Self-reported average fatigue for the last week scored on 0-100 numerical rating scale where 0 = "no fatigue" and 100 = "the greatest imaginable." A higher score means a worse outcome. | Mean | Standard Deviation | units on a scale |
|
| Number of Participants Stratified per Graded Chronic Pain Scale (GCPS) grade | Individuals were classified into 6 chronic pain grades: 0 = no pain; I = low pain intensity and low pain-related disability; IIa = high pain intensity and low pain-related disability; IIb = high pain intensity and high activity interference; III = moderate pain-related disability; and IV = severe pain-related disability. For analyses, this variable was dichotomized: grades 0-IIa were combined in one category and all higher grades in another. A higher grade means a worse outcome. | Count of Participants | Participants |
|
| The Jaw Functional Limitation Scale (JFLS) Global Score | The JFLS contains 20 items that measure limitations across mastication, vertical jaw mobility, and verbal/emotional expression rated on a 0-10 scale where 0 = "no limitation" and 10 = "severe limitation." The Global Score is computed as the mean response for all items and ranges from 0 to 10. A higher score means a worse outcome. | Mean | Standard Deviation | units on a scale |
|
| The Headache Impact Test (HIT-6) Global Score | The HIT-6 contains 6 items and assesses headache-related disability by the frequency of daily activity limitations ranging from "never" to "always." The 6 item scores are summed to yield a global score ranging from 36 to 78. A higher score means a worse outcome. | Mean | Standard Deviation | units on a scale |
|
| The Perceived Stress Scale (PSS) Global Score | The PSS assesses the frequency of 14 sources of stress on a scale from 0 = "never" to 4 = "very often." The item scores are summed to yield a Global Score ranging from 0 to 56. A higher score means a worse outcome. | Mean | Standard Deviation | units on a scale |
|
| The Pittsburgh Sleep Quality Index (PSQI) Global Score | The PSQI has 19 items grouped into 7 component scores, each weighted equally on a 0-3 scale, The 7 component scores are summed to yield a global PSQI score, which has a range of 0-21. A higher score means a worse outcome. | Mean | Standard Deviation | units on a scale |
|
| The Hospital Anxiety and Depression Scale (HADS) Anxiety Score | The HADS is a 14-item assessment of anxiety (7 items) and depression (7 items) using the relative frequency of symptoms over the past week, rated on a 4-point scale ranging from 0 = "not at all" to 3 = "very often indeed". Responses are summed to provide separate scores for anxiety and depression (range from 0 to 21 for each subscale). A higher score means a worse outcome. | Mean | Standard Deviation | units on a scale |
|
| The Hospital Anxiety and Depression Scale (HADS) Depression Score | The HADS is a 14-item assessment of anxiety (7 items) and depression (7 items) using the relative frequency of symptoms over the past week, rated on a 4-point scale ranging from 0 = "not at all" to 3 = "very often indeed". Responses are summed to provide separate scores for anxiety and depression (range from 0 to 21 for each subscale). A higher score means a worse outcome. | Mean | Standard Deviation | units on a scale |
|
| The Symptom Checklist 90-Revised (SCL-90R) Somatization Scale Score | The SCL-90R Somatization Scale is a 12-item assessment of somatic symptom distress over the past 7 days rated from 0 = "not at all" to 4 = "extremely." The scale score is computed as the mean for all items. The score range is from 0 to 4. The higher score means a worse outcome. | Mean | Standard Deviation | units on a scale |
|
| The SF-12 Health Survey v2 (SF-12v2) Physical Component Summary (PCS) | The SF-12v2 v2 contains 7 questions assessing 8 domains of functioning and well-being rated from: "excellent" to "poor" (for general health); "yes, limited a lot" to "no, not limited at all" (for functional level); and "all of the time" to "none of the time" (for emotional state). These 8 domains can be further summarized into a physical component summary (PCS) and a mental component summary (MCS). The range for each component is 0-100 and a higher score means a better outcome. | Mean | Standard Deviation | units on a scale |
|
| The SF-12 Health Survey v2 (SF-12v2) Mental Component Summary (MCS) | The SF-12v2 v2 contains 7 questions assessing 8 domains of functioning and well-being rated from: "excellent" to "poor" (for general health); "yes, limited a lot" to "no, not limited at all" (for functional level); and "all of the time" to "none of the time" (for emotional state). These 8 domains can be further summarized into a physical component summary (PCS) and a mental component summary (MCS). The range for each component is 0-100 and a higher score means a better outcome. | Mean | Standard Deviation | units on a scale |
|
| Thermal Pain Threshold | Temperature values, measured in degrees Celsius, from 4 examiner-applied contact heat stimuli are averaged to measure the experimental thermal pain threshold (temperature at which pain is first perceived). The range was 32-50 degrees Celsius and a higher value means a better outcome. | Mean | Standard Deviation | degrees Celsius |
|
| Thermal Pain Tolerance | Temperature values, measured in degrees Celsius, from 4 examiner-applied contact heat stimuli are averaged to measure the experimental thermal pain tolerance (temperature at which pain can no longer be tolerated). The range was 32-50 degrees Celsius and a higher value means a better outcome. | Mean | Standard Deviation | degrees Celsius |
|
| Pressure Pain Threshold at Temporalis Muscle | Pressure values, measured in kiloPascals (kPa), from up to 5 experimental pressure stimuli, bilaterally applied to the area of temporalis muscle, are averaged to obtain a single pressure pain threshold value per anatomical site. The range is 0-500 kPa and a higher value means a better outcome. | Mean | Standard Deviation | kPa |
|
| Pressure Pain Threshold at Masseter Muscle | Pressure values, measured in kiloPascals (kPa), from up to 5 experimental pressure stimuli, bilaterally applied to the area of masseter muscle, are averaged to obtain a single pressure pain threshold value per anatomical site. The range is 0-500 kPa and a higher value means a better outcome. | Mean | Standard Deviation | kPa |
|
| Pressure Pain Threshold at Temporomandibular Joint | Pressure values, measured in kiloPascals (kPa), from up to 5 experimental pressure stimuli, bilaterally applied to the area of temporomandibular joint, are averaged to obtain a single pressure pain threshold value per anatomical site. The range is 0-500 kPa and a higher value means a better outcome. | Mean | Standard Deviation | kPa |
|
| Pressure Pain Threshold at Trapezius Muscle | Pressure values, measured in kiloPascals (kPa), from up to 5 experimental pressure stimuli, bilaterally applied to the area of trapezius muscle, are averaged to obtain a single pressure pain threshold value per anatomical site. The range is 0-500 kPa and a higher value means a better outcome. | Mean | Standard Deviation | kPa |
|
| Pressure Pain Threshold at Lateral Epicondyle | Pressure values, measured in kiloPascals (kPa), from up to 5 experimental pressure stimuli, bilaterally applied to the area of lateral epicondyle, are averaged to obtain a single pressure pain threshold value per anatomical site. The range is 0-500 kPa and a higher value means a better outcome. | Mean | Standard Deviation | kPa |
|
| Pain-free Jaw Opening | Measured at TMD exam. A higher value means a better outcome. | Mean | Standard Deviation | mm |
|
| Maximum Unassisted Jaw Opening | Measured at TMD exam. A higher value means a better outcome. | Mean | Standard Deviation | mm |
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| Maximum Assisted Jaw Opening | Measured at TMD exam. A higher value means a better outcome. | Mean | Standard Deviation | mm |
|
| Systolic Blood Pressure | Average of 3 repeated measures taken with a 2-minute interval. | Mean | Standard Deviation | mm Hg |
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| Diastolic Blood pressure | Average of 3 repeated measures taken with a 2-minute interval. | Mean | Standard Deviation | mm Hg |
|
| Heart Rate | Average of 3 repeated measures taken with a 2-minute interval. | Mean | Standard Deviation | beats per minute |
|
Propranolol hydrochloride extended release (ER) capsules; 60 mg (Visit 1 and Visit 4); 120 mg (Visit 2 and Visit 3) given orally as: 60 mg once/day (Visit 1 and Visit 4) and 60 mg twice/day (Visit 2 and Visit 3).
Propranolol ER: Capsules given orally according to schedule at Visit 1, Visit 2, Visit 3, and Visit 4.
| OG001 | Placebo | Capsules, identical in appearance to active comparator (propranolol), to be administered orally in exactly the same manner as propranolol at Visit 1 (once/day), Visit 2 (twice/day), Visit 3 (twice/day), and Visit 4 (once/day). Placebo: Gelatin capsules with a microcrystalline cellulose filler manufactured to mimic propranolol ER 60 mg capsules |
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| Secondary | Change in the Weekly Mean Pain Intensity After 9 Weeks of Treatment | Weekly mean pain intensity computed as the arithmetic mean of daily pain intensity values during the week prior to randomization and prior to each study visit. Daily pain intensity is measured on 0-100 numeric rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable") as reported in the Daily Symptom Diary. A higher score means a worse outcome. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Change in the Weekly Mean Pain Duration After 9 Weeks of Treatment | Weekly mean pain duration computed as the arithmetic mean of daily pain duration values during the week prior to randomization and prior to each study visit. Daily pain duration is measured on 0-100 percentage scale where percent = "percent of waking day you had facial pain" as reported in the Daily Symptom Diary. A higher score means a worse outcome. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Change in the SF-McGill Pain Questionnaire Affective Component After 9 Weeks of Treatment | The SF-McGill Pain Questionnaire contains 4 affective descriptors rated on a 0-3 scale where 0 = "none," 1 = "mild," 2 = "moderate," and 3 = "severe." The item scores are summed to yield a total score ranging from 0 to 12. A higher score means a worse outcome. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Change in the SF-McGill Pain Questionnaire Sensory Component After 9 Weeks of Treatment | The SF-McGill Pain Questionnaire contains 11 sensory descriptors rated on a 0-3 scale where 0 = "none," 1 = "mild," 2 = "moderate," and 3 = "severe." The item scores are summed to yield a total score ranging from 0 to 33. A higher score means a worse outcome. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Change in the SF-McGill Pain Questionnaire Present Facial Pain Intensity After 9 Weeks of Treatment | Self-reported present intensity of facial pain at the moment of assessment scored on a descriptive scale where 1 = "no pain' and 6 = "excruciating pain." A higher score means worse outcome. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Change in the SF-McGill Pain Questionnaire Weekly Average Facial Pain Intensity After 9 Weeks of Treatment | Self-reported average facial pain intensity for the last week scored on 0-100 numerical rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable". A higher score means a worse outcome. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Change in the SF-McGill Pain Questionnaire Weekly Average Facial Pain Duration After 9 Weeks of Treatment | Self-reported average facial pain duration for the last week scored on 0-100 percentage scale where percent = "percent of waking day you had facial pain". A higher score means a worse outcome. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Change in the SF-McGill Pain Questionnaire Weekly Fatigue After 9 Weeks of Treatment | Self-reported average fatigue for the last week scored on 0-100 numerical rating scale where 0 = "no fatigue" and 100 = "the greatest imaginable." A higher score means a worse outcome. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Number of Participants Stratified Per Graded Chronic Pain Scale (GCPS) Grade After 9 Weeks of Treatment | Individuals were classified into 6 chronic pain grades: 0 = no pain; I = low pain intensity and low pain-related disability; IIa = high pain intensity and low pain-related disability; IIb = high pain intensity and high activity interference; III = moderate pain-related disability; and IV = severe pain-related disability. For analyses, this variable was dichotomized: grades 0-IIa were combined in one category and all higher grades in another. A higher grade means a worse outcome. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Count of Participants | Participants | Visit 4 (study day 63 +/-7) |
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| Secondary | Change in the Jaw Functional Limitation Scale (JFLS) Global Score After 9 Weeks of Treatment | The JFLS contains 20 items that measure limitations across mastication, vertical jaw mobility, and verbal/emotional expression rated on a 0-10 scale where 0 = "no limitation" and 10 = "severe limitation." The Global Score is computed as the mean response for all items and ranges from 0 to 10. A higher score means a worse outcome. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Change in the Headache Impact Test (HIT-6) Global Score After 9 Weeks of Treatment | The HIT-6 contains 6 items and assesses headache-related disability by the frequency of daily activity limitations ranging from "never" to "always." The 6 item scores are summed to yield a global score ranging from 36 to 78. A higher score means a worse outcome. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Change in the Pittsburgh Sleep Quality Index (PSQI) Global Score After 9 Weeks of Treatment | The PSQI has 19 items grouped into 7 component scores, each weighted equally on a 0-3 scale, The 7 component scores are summed to yield a global PSQI score, which has a range of 0-21. A higher score means a worse outcome. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Number of Participants Stratified Per Dichotomized Score From the Patient Global Impression of Change (PGIC) Scale After 9 Weeks of Treatment | The PGIC scale assesses patient overall change in the severity of illness following treatment. Participants rate how they feel now compared with how they felt before receiving study drug on a 7-point scale where 0 = "No change or condition has got worse" and 6 = "A great deal better." A higher score means a better outcome. For analyses, this variable was dichotomized: scores from 0 to 3 were combined in one category of "No" (no significant improvement) and scores from 4 to 6 were combined in another category of "Yes" (significant improvement with the study treatment). | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Count of Participants | Participants | Visit 4 (study day 63 +/-7) |
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| Secondary | Change in the Perceived Stress Scale (PSS) Global Score After 9 Weeks of Treatment | The PSS assesses the frequency of 14 sources of stress on a scale from 0 = "never" to 4 = "very often." The item scores are summed to yield a global score ranging from 0 to 56. A higher score means a worse outcome. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Change in the Hospital Anxiety and Depression Scale (HADS) Depression Score After 9 Weeks of Treatment | The HADS is a 14-item assessment of anxiety (7 items) and depression (7 items) using the relative frequency of symptoms over the past week, rated on a 4-point scale ranging from 0 = "not at all" to 3 = "very often indeed". Responses are summed to provide separate scores for anxiety and depression with a range from 0 to 21. A higher score means a worse outcome. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Change in the Hospital Anxiety and Depression Scale (HADS) Anxiety Score After 9 Weeks of Treatment | The HADS is a 14-item assessment of anxiety (7 items) and depression (7 items) using the relative frequency of symptoms over the past week, rated on a 4-point scale ranging from 0 = "not at all" to 3 = "very often indeed". Responses are summed to provide separate scores for anxiety and depression with a range from 0 to 21. A higher score means a worse outcome. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Change in the Symptom Checklist 90-Revised (SCL-90R) Somatization Scale Score After 9 Weeks of Treatment | The SCL-90R Somatization Scale is a 12-item assessment of somatic symptom distress over the past 7 days rated from 0 = "not at all" to 4 = "extremely." The scale score is computed as the mean for all items. The score range is from 0 to 4. A higher score means a worse outcome. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Change in the SF-12 Health Survey v2 (SF-12v2) Physical Component Summary (PCS) After 9 Weeks of Treatment | The SF-12v2 contains 7 questions assessing 8 domains of functioning and well-being rated from: "excellent" to "poor" (for general health); "yes, limited a lot" to "no, not limited at all" (for functional level); and "all of the time" to "none of the time" (for emotional state). These 8 domains can be further summarized into a physical component summary (PCS) and a mental component summary (MCS). summary (MCS). The range for each component is 0-100 and a higher score means a better outcome. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Change in the SF-12 Health Survey v2 (SF-12v2) Mental Component Summary (MCS) After 9 Weeks of Treatment | The SF-12v2 contains 7 questions assessing 8 domains of functioning and well-being rated from: "excellent" to "poor" (for general health); "yes, limited a lot" to "no, not limited at all" (for functional level); and "all of the time" to "none of the time" (for emotional state). These 8 domains can be further summarized into a physical component summary (PCS) and a mental component summary (MCS). The range for each component is 0-100 and a higher score means a better outcome. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Change in Thermal Pain Threshold After 9 Weeks of Treatment | Temperature values, measured in degrees Celsius, from 4 examiner-applied contact heat stimuli will be averaged to measure the experimental thermal pain threshold (temperature at which pain is first perceived). The range was 32-50 degrees Celsius and a higher value means a better outcome. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | degrees Celsius | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Change in Thermal Pain Tolerance After 9 Weeks of Treatment | Temperature values, measured in degrees Celsius, from 4 examiner-applied contact heat stimuli will be averaged to measure the experimental thermal pain tolerance (temperature at which pain can no longer be tolerated). The range was 32-50 degrees Celsius and a higher value means a better outcome. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | degrees Celsius | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Change in Pressure Pain Threshold at Temporalis Muscle After 9 Weeks of Treatment | Pressure values, measured in kilopascals (kPa), from up to 5 experimental pressure stimuli, bilaterally applied to the area of temporalis muscle, are averaged to obtain a single pressure pain threshold value per anatomical site. The range is 0-500 kPa and a higher value means a better outcome. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | kPa | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Change in Pressure Pain Threshold at Masseter Muscle After 9 Weeks of Treatment | Pressure values, measured in kilopascals, from up to 5 experimental pressure stimuli, bilaterally applied to the area of masseter muscle, will be averaged to obtain a single pressure pain threshold value per anatomical site. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | kPa | Visit 1 (study day 0) and Visit 4 (study day 63 +/- 7) |
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| Secondary | Change in Pressure Pain Threshold at Temporomandibular Joint After 9 Weeks of Treatment | Pressure values, measured in kilopascals, from up to 5 experimental pressure stimuli, bilaterally applied to the area of temporomandibular joint, will be averaged to obtain a single pressure pain threshold value per anatomical site. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | kPa | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Change in Pressure Pain Threshold at Trapezius Muscle After 9 Weeks of Treatment | Pressure values, measured in kilopascals, from up to 5 experimental pressure stimuli, bilaterally applied to the area of trapezius muscle, will be averaged to obtain a single pressure pain threshold value per anatomical site. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | kPa | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Change in Pressure Pain Threshold at Lateral Epicondyle After 9 Weeks of Treatment | Pressure values, measured in kilopascals, from up to 5 experimental pressure stimuli, bilaterally applied to the area of lateral epicondyle, will be averaged to obtain a single pressure pain threshold value per anatomical site. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | kPa | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Change in Pain-free Jaw Opening After 9 Weeks of Treatment | Measured at TMD exam. A higher value means a better outcome. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | mm | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Change in Maximum Unassisted Jaw Opening After 9 Weeks of Treatment | Measured at TMD exam. A higher value means a better outcome. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | mm | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Change in Maximum Assisted Jaw Opening After 9 Weeks of Treatment | Measured at TMD exam. A higher value means a better outcome. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | mm | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Change in Systolic Blood Pressure After 9 Weeks of Treatment | Average of 3 repeated measures taken with a 2-minute interval. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | mm Hg | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Secondary | Change in Diastolic Blood Pressure After 9 Weeks of Treatment | Average of 3 repeated measures taken with a 2-minute interval. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | mm Hg | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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|
|
| Secondary | Change in Heart Rate After 9 Weeks of Treatment | Average of 3 repeated measures taken with a 2-minute interval. | All participants who received at least one dose of study medication and provided at least one post-baseline outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | beats per minute | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Other Pre-specified | Change in the Weekly Mean Pain Index After 9 Weeks of Treatment Stratified Per Number of COMT LPS Haplotypes | Weekly mean pain index computed as the arithmetic mean of daily pain index values during the week prior to randomization and prior to each study visit. Daily pain index is computed as pain intensity (0-100 numeric rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable") multiplied by pain duration (0-100 percentage scale where percent = "percent of waking day you had facial pain") as reported in the Daily Symptom Diary, divided by 100. The pain index range is from 0 to 100. A higher score means a worse outcome. The pain index was stratified per number of catechol-O-methyltransferase (COMT) Low Pain Sensitive (LPS) haplotypes. | All participants who received at least one dose of study medication, provided at least one post-baseline outcome measure, and had genotyping data for COMT haplotypes. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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| Other Pre-specified | Change in the Weekly Mean Pain Index After 9 Weeks of Treatment Stratified Per Number of COMT Valine Alleles at rs4680 | Weekly mean pain index computed as the arithmetic mean of daily pain index values during the week prior to randomization and prior to each study visit. Daily pain index is computed as pain intensity (0-100 numeric rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable") multiplied by pain duration (0-100 percentage scale where percent = "percent of waking day you had facial pain") as reported in the Daily Symptom Diary, divided by 100. The pain index range is from 0 to 100. A higher score means a worse outcome. The pain index was stratified per number of catechol-O-methyltransferase (COMT) valine alleles at single nucleotide polymorphism (SNP) rs4680. | All participants who received at least one dose of study medication, provided at least one post-baseline outcome measure, and had genotyping data for COMT rs4680. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) |
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|
|
| 1 |
| 100 |
| 4 |
| 100 |
| 86 |
| 100 |
| EG001 | Placebo | Capsules, identical in appearance to active comparator (propranolol), to be administered orally in exactly the same manner as propranolol at Visit 1 (once/day), Visit 2 (twice/day), Visit 3 (twice/day), and Visit 4 (once/day). Placebo: Gelatin capsules with a microcrystalline cellulose filler manufactured to mimic propranolol ER 60 mg capsules | 0 | 100 | 1 | 100 | 75 | 100 |
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| Breast cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (18.0) | Non-systematic Assessment |
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| Mental status changes | Psychiatric disorders | MedDRA (18.0) | Non-systematic Assessment | Occurred in a participant with metastatic breast cancer |
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| Acute kidney injury | Renal and urinary disorders | MedDRA (18.0) | Non-systematic Assessment |
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| Depression | Psychiatric disorders | MedDRA (18.0) | Systematic Assessment |
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| Appendicitis | Infections and infestations | MedDRA (18.0) | Non-systematic Assessment |
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| Crohn's disease | Gastrointestinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| Alcohol abuse | Psychiatric disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| Suicide attempt | Psychiatric disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| Suicidal ideation | Psychiatric disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (18.0) | Non-systematic Assessment |
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| Fatigue | General disorders | MedDRA (18.0) | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
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| Hypoaestesia | Nervous system disorders | MedDRA (18.0) | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (18.0) | Non-systematic Assessment |
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| Migraine | Nervous system disorders | MedDRA (18.0) | Non-systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (18.0) | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (18.0) | Non-systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA (18.0) | Systematic Assessment |
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| Depression | Psychiatric disorders | MedDRA (18.0) | Systematic Assessment |
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| Sleep disorder | Psychiatric disorders | MedDRA (18.0) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Non-systematic Assessment |
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| Injury | Injury, poisoning and procedural complications | MedDRA (18.0) | Non-systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| Skin and subcutaneos tissue disorders | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| Respiratory, thoracic and mediastinal disorders | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
Not provided
Not provided
| D007592 |
| Joint Diseases |
| D009135 | Muscular Diseases |
| D009057 | Stomatognathic Diseases |
| D009930 |
| Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D002241 | Carbohydrates |
| 1 LPS haplotype |
|
|
| 2 LPS haplotypes |
|
|
| 1 valine allele |
|
|
| 2 valine alleles |
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|