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| Name | Class |
|---|---|
| Jazz Pharmaceuticals | INDUSTRY |
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This study is the first clinical trial using sodium oxybate for the treatment of REM sleep behavior disorder (RBD). Sodium oxybate is a drug approved by FDA for the treatment of narcolepsy which has been used "off label" to treat patients with severe RBD. This drug has shown to be effective and well tolerated in patients with RBD (Shneerson, 2009; Liebenthal, 2016; Moghadam, 2017).
Rapid eye movement sleep behavior disorder (RBD) is a condition resulting in violent dream-enactment during sleep which affects millions of individuals in the United States, however therapies for RBD are limited and cause significant side effects. As a result, despite using a combination of drugs, a large number of patients with RBD continue to act out violent dreams causing severe self-injuries or injuries to their bed partners. Prior studies and our experience have shown that sodium oxybate can be effective in these cases of treatment-resistant RBD. This study would therefore evaluate the efficacy and tolerance of sodium oxybate in this patient population.
This study is an 8-week trial comparing sodium oxybate versus placebo randomly assigned to patients with treatment-resistant RBD, i.e. individuals who have insufficiently responded or tolerated melatonin and clonazepam. The study uses a double-blind design (participants, staff, and investigators will not know which drug between active drug and placebo is given to participants), and will measure treatment efficacy based on patients, partners and clinicians report, and objective outcomes based on in-home actigraphy and in-lab polysomnography before and after intervention.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sodium Oxybate (SXB) arm | Active Comparator | Sodium Oxybate (SXB) will be dispensed to the participants. |
|
| Placebo (PBO) arm | Placebo Comparator | Placebo will be dispensed to the participants. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sodium Oxybate | Drug | Sodium Oxybate will be titrated up weekly by 1.5g nightly dose increments from an initial 4.5g total nightly dose (which could be given in two unequal doses if needed, or one single dose no greater than 4.5g) to an optimal individual dose based on clinical response on RBD symptoms and tolerance, to a maximum nightly dose of 9g ("flexible dose" period lasting up to 8 weeks). The optimal dose will then be continued for at least 4 weeks ("stable dose"). |
| Measure | Description | Time Frame |
|---|---|---|
| Number of RBD Episodes in One Month (Per Patient RBD Log) | Patients record any episode of dream enactment, such as talking, shouting, kicking, or punching, etc. | Assessed for 28 days at baseline and during last month of treatment (total treatment period of up to 12 weeks) |
| Number of Severe of RBD Episodes in One Month (Per Patient RBD Log) | Patients record any episode of dream enactment, such as talking, shouting, kicking, or punching, etc. Severity is scored from 1 to 3 (1: least severe, 3 most severe):
The number of injurious (severe) episodes is reported. | Assessed for 28 days at baseline and during last month of treatment (total treatment period of up to 12 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Responders According to the CGI Efficacy Scale (CGI-E) | Clinical Global Impression-Efficacy index (CGI-E) is a 4x4 rating scale that assesses the therapeutic effect (Marked, Moderate, Minimal, Unchanged or worse) of treatment medication and associated side effects (none, do not significantly interfere with patient's functioning, significantly interfere with patient's functioning, Outweigh therapeutic effect). Therapeutic effect: Marked and Side effects: None is the best. Therapeutic effect: Unchanged or worse and Side effects: outweigh therapeutic effect is the worst. Each combination of an estimated therapeutic effect and side effect is assigned a score from 1-16, 1 being the best, 16 being the worst. Participants scoring below 4 were considered to be "responders." |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Emmanuel During, MD | Stanford University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University | Palo Alto | California | 94306 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19483483 | Background | Shneerson JM. Successful treatment of REM sleep behavior disorder with sodium oxybate. Clin Neuropharmacol. 2009 May-Jun;32(3):158-9. doi: 10.1097/WNF.0b013e318193e394. | |
| 26595534 | Background | Liebenthal J, Valerio J, Ruoff C, Mahowald M. A Case of Rapid Eye Movement Sleep Behavior Disorder in Parkinson Disease Treated With Sodium Oxybate. JAMA Neurol. 2016 Jan;73(1):126-7. doi: 10.1001/jamaneurol.2015.2904. No abstract available. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Sodium Oxybate (SXB) Arm | For each participant, Sodium Oxybate (SXB) starting at a 4.5g total nightly dose then titrated up weekly by 1.5g increments over 8 weeks to establish their optimal individualized dose (based on their clinical response on RBD symptoms and tolerance). Participant then receive their optimal dose for at least 4 weeks. |
| FG001 | Placebo (PBO) Arm | Placebo similar in appearance, smell and flavor so that it is indistinguishable from sodium oxybate. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Sodium Oxybate (SXB) Arm | For each participant, Sodium Oxybate (SXB) starting at a 4.5g total nightly dose then titrated up weekly by 1.5g increments over 8 weeks to establish their optimal individualized dose (based on their clinical response on RBD symptoms and tolerance). Participant then receive their optimal dose for at least 4 weeks. |
| 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 | Number of RBD Episodes in One Month (Per Patient RBD Log) | Patients record any episode of dream enactment, such as talking, shouting, kicking, or punching, etc. | Participants with data at each time point are included in the analysis | Posted | Median | Inter-Quartile Range | episodes | Assessed for 28 days at baseline and during last month of treatment (total treatment period of up to 12 weeks) |
|
Up to 12 weeks
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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 | Sodium Oxybate (SXB) Arm | For each participant, Sodium Oxybate (SXB) starting at a 4.5g total nightly dose then titrated up weekly by 1.5g increments over 8 weeks to establish their optimal individualized dose (based on their clinical response on RBD symptoms and tolerance). Participant then receive their optimal dose for at least 4 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Myoclonus episode | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anxiety | Psychiatric disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Emmanuel During | Stanford University | 212-844-8888 | Emmanuel.During@mountsinai.org |
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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 | Jul 8, 2020 | Jan 11, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 11, 2023 | Jan 11, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D020187 | REM Sleep Behavior Disorder |
| D010300 | Parkinson Disease |
| ID | Term |
|---|---|
| D020923 | REM Sleep Parasomnias |
| D020447 | Parasomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D012978 | Sodium Oxybate |
| ID | Term |
|---|---|
| D006885 | Hydroxybutyrates |
| D002087 | Butyrates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
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Randomized, double-blind, placebo-controlled trial
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|
| Placebo | Other | Placebo will be similar in appearance, smell and flavor to the subjects, so that the investigators and participants will be unable to distinguish it from sodium oxybate. |
|
| Assessed at week 12 (end of treatment period). |
| Number of Responders According to the CGI Improvement Scale (CGI-I) | Clinical Global Impression-Improvement scale (CGI-I) is a 7-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention and rated as: 1. Very much improved, 2. Much improved, 3. Minimally improved, 4. No change, 5. Minimally worse, 6. Much worse, 7. Very much worse. 1 is the best and 7 is the worst. Participants scoring below 4 were considered to be "responders." | Assessed at week 12 (end of treatment period). |
| Epworth Sleepiness Scale (ESS) Score | Epworth Sleepiness Scale (ESS) is a scale to assess patients' general level of sleepiness. Patients choose the most appropriate number (0=would never doze, 1=slight chance of dozing, 2=moderate chance of dozing, 3=high chance of dozing) for the each situation: Sitting and reading, Watching TV, Sitting and inactive in a public place, As a passenger in a car for an hour, Lying down to rest in the afternoon, Sitting and talking to someone, Sitting quietly after a lunch, While stopped for a few minutes in the traffic in a car. 0-10: Normal range, 10-12: Borderline, 12-24: Abnormal. Participants recorded their scores for 28 days at baseline and during the 28 days leading up to week 12; scores were then averaged to calculate the score for each time point per participant, and then the median for all participants is reported. | Assessed at baseline and week 12 |
| RBD Episode Severity and Frequency During REM Sleep by Quantitative Video-PSG (Polysomnography) Analysis Per 10 Minutes of REM Sleep | The average number of dream-enactment episodes (resulting in motor behaviors, or movements) weighted for severity. Frequency and severity were calculated as the sum of RBD episodes (frequency) times severity (mild = 1; moderate = 5, severe = 10) occurring over one night's sleep, then averaged to calculate the number of episodes per 10 minutes of REM sleep. | Assessed at baseline and week 12 (average approximately 8 hours to assess at each time point) |
| Change in Ambulatory Measures of Movements During Sleep Using Actigraphy | Measure of "activity score" using in-home 4-week actigraphy | Assessed for 28 days at baseline and during last month of treatment (total treatment period of up to 12 weeks) |
| 28366329 | Background | Moghadam KK, Pizza F, Primavera A, Ferri R, Plazzi G. Sodium oxybate for idiopathic REM sleep behavior disorder: a report on two patients. Sleep Med. 2017 Apr;32:16-21. doi: 10.1016/j.sleep.2016.04.014. Epub 2016 Jun 7. |
| 37052688 | Derived | During EH, Hernandez B, Miglis MG, Sum-Ping O, Hekmat A, Cahuas A, Ekelmans A, Yoshino F, Mignot E, Kushida CA. Sodium oxybate in treatment-resistant rapid-eye-movement sleep behavior disorder. Sleep. 2023 Aug 14;46(8):zsad103. doi: 10.1093/sleep/zsad103. |
| BG001 |
| Placebo (PBO) Arm |
Placebo similar in appearance, smell and flavor so that it is indistinguishable from sodium oxybate. |
| 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 |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
|
| RBD Symptom Duration | Mean | Standard Deviation | years |
|
| History of Injuries | Injuries related to REM Sleep Behavior Disorder | Count of Participants | Participants |
|
| Parkinson disease | Count of Participants | Participants |
|
| Sleep Apnea | Count of Participants | Participants |
|
| Insomnia | Count of Participants | Participants |
|
| Current Treatment | Participant's current treatment can include more than 1 medication. | Count of Participants | Participants |
|
| Placebo (PBO) Arm |
Placebo similar in appearance, smell and flavor so that it is indistinguishable from sodium oxybate. |
|
|
|
| Primary | Number of Severe of RBD Episodes in One Month (Per Patient RBD Log) | Patients record any episode of dream enactment, such as talking, shouting, kicking, or punching, etc. Severity is scored from 1 to 3 (1: least severe, 3 most severe):
The number of injurious (severe) episodes is reported. | Participants with data at each time point are included in the analysis | Posted | Median | Inter-Quartile Range | episodes | Assessed for 28 days at baseline and during last month of treatment (total treatment period of up to 12 weeks) |
|
|
|
|
| Secondary | Number of Responders According to the CGI Efficacy Scale (CGI-E) | Clinical Global Impression-Efficacy index (CGI-E) is a 4x4 rating scale that assesses the therapeutic effect (Marked, Moderate, Minimal, Unchanged or worse) of treatment medication and associated side effects (none, do not significantly interfere with patient's functioning, significantly interfere with patient's functioning, Outweigh therapeutic effect). Therapeutic effect: Marked and Side effects: None is the best. Therapeutic effect: Unchanged or worse and Side effects: outweigh therapeutic effect is the worst. Each combination of an estimated therapeutic effect and side effect is assigned a score from 1-16, 1 being the best, 16 being the worst. Participants scoring below 4 were considered to be "responders." | Posted | Count of Participants | Participants | Assessed at week 12 (end of treatment period). |
|
|
|
|
| Secondary | Number of Responders According to the CGI Improvement Scale (CGI-I) | Clinical Global Impression-Improvement scale (CGI-I) is a 7-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention and rated as: 1. Very much improved, 2. Much improved, 3. Minimally improved, 4. No change, 5. Minimally worse, 6. Much worse, 7. Very much worse. 1 is the best and 7 is the worst. Participants scoring below 4 were considered to be "responders." | Posted | Count of Participants | Participants | Assessed at week 12 (end of treatment period). |
|
|
|
|
| Secondary | Epworth Sleepiness Scale (ESS) Score | Epworth Sleepiness Scale (ESS) is a scale to assess patients' general level of sleepiness. Patients choose the most appropriate number (0=would never doze, 1=slight chance of dozing, 2=moderate chance of dozing, 3=high chance of dozing) for the each situation: Sitting and reading, Watching TV, Sitting and inactive in a public place, As a passenger in a car for an hour, Lying down to rest in the afternoon, Sitting and talking to someone, Sitting quietly after a lunch, While stopped for a few minutes in the traffic in a car. 0-10: Normal range, 10-12: Borderline, 12-24: Abnormal. Participants recorded their scores for 28 days at baseline and during the 28 days leading up to week 12; scores were then averaged to calculate the score for each time point per participant, and then the median for all participants is reported. | Participants with data at each time point are included in the analysis | Posted | Median | Inter-Quartile Range | score on a scale | Assessed at baseline and week 12 |
|
|
|
|
| Secondary | RBD Episode Severity and Frequency During REM Sleep by Quantitative Video-PSG (Polysomnography) Analysis Per 10 Minutes of REM Sleep | The average number of dream-enactment episodes (resulting in motor behaviors, or movements) weighted for severity. Frequency and severity were calculated as the sum of RBD episodes (frequency) times severity (mild = 1; moderate = 5, severe = 10) occurring over one night's sleep, then averaged to calculate the number of episodes per 10 minutes of REM sleep. | Participants with data available at the respective time points are presented. | Posted | Mean | Standard Deviation | episodes*severity per 10 minutes of REM | Assessed at baseline and week 12 (average approximately 8 hours to assess at each time point) |
|
|
|
|
| Secondary | Change in Ambulatory Measures of Movements During Sleep Using Actigraphy | Measure of "activity score" using in-home 4-week actigraphy | Analysis was not possible because the data that were collected were corrupted and uninterpretable. | Posted | Assessed for 28 days at baseline and during last month of treatment (total treatment period of up to 12 weeks) |
|
|
| 0 |
| 12 |
| 5 |
| 12 |
| 7 |
| 12 |
| EG001 | Placebo (PBO) Arm | Placebo similar in appearance, smell and flavor so that it is indistinguishable from sodium oxybate. | 0 | 12 | 0 | 12 | 2 | 12 |
| Sleep terror | Psychiatric disorders | Systematic Assessment |
|
| Suicidal ideation | Psychiatric disorders | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | Systematic Assessment |
|
| Dizziness | Nervous system disorders | Systematic Assessment |
|
| Asthenia | General disorders | Systematic Assessment |
|
| Auditory hallucination | Psychiatric disorders | Systematic Assessment |
|
| Brain fog | General disorders | Systematic Assessment |
|
| Enuresis | Renal and urinary disorders | Systematic Assessment |
|
| Gastrointestinal discomfort | Gastrointestinal disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Hot flashes | General disorders | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Sensation of being "wired" | General disorders | Systematic Assessment |
|
| Tremor | Nervous system disorders | Systematic Assessment |
|
| Anorexia | Psychiatric disorders | Systematic Assessment |
|
| Catathrenia | General disorders | Systematic Assessment |
|
| Increased sweating | General disorders | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | Systematic Assessment |
|
| Dysgeusia | Gastrointestinal disorders | Systematic Assessment |
|
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| D001523 |
| Mental Disorders |
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
| D009930 |
| Organic Chemicals |
| D006880 | Hydroxy Acids |
| Final dose |
|
|
| Wilcoxon Signed Rank test |
| 0.83 |
| Median Difference (Net) |
| 0.0 |
| 2-Sided |
| 95 |
| -1.0 |
| 1.0 |
| Other |
| Between group analysis of change from baseline. | Mann Whitney U test | 0.09 | All statistical tests were conducted using a 2-sided alpha level of 0.05. | Median Difference (Net) | -1.0 | 2-Sided | 95 | -3.5 | 0.0 | Superiority |
| Final dose |
|
|
Within group analysis of change from baseline.
| Wilcoxon Signed Rank test |
| 0.43 |
All statistical tests were conducted using a 2-sided alpha level of 0.05. |
| Median Difference (Final Values) |
| -0.5 |
| 2-Sided |
| 95 |
| -3.5 |
| 2.0 |
| Other |
| Between group analysis of change from baseline. | Mann Whitney U test | 0.65 | All statistical tests were conducted using a 2-sided alpha level of 0.05. | Median Difference (Final Values) | -0.5 | 2-Sided | 95 | -4.0 | 3.0 | Superiority |
| Final dose |
|
|
| Unpaired T-test |
| 0.95 |
All statistical tests were conducted using a 2-sided alpha level of 0.05. |
| Mean Difference (Net) |
| 0.2 |
| 2-Sided |
| 95 |
| -4.6 |
| 4.5 |
| Other |
| Between group analysis of change from baseline. | Paired T-test | 0.22 | All statistical tests were conducted using a 2-sided alpha level of 0.05. | Mean Difference (Net) | -6.4 | 2-Sided | 95 | -16.2 | 3.1 | Superiority |