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Sleep disturbances are cardinal features of Veterans with post traumatic stress disorder (PTSD). In particular, obstructive sleep apnea is reported to occur more frequently in patients with PTSD compared to those without PTSD and contribute to worsening cognitive and behavioral functions. Continuous positive airway pressure (CPAP) is considered the treatment of choice for OSA but adherence to CPAP in Veterans with PTSD is poor compared to the general population. The proposed study aims at comparing the efficacy, tolerability, and adherence of oral appliances-an alternative therapy to OSA- to CPAP. The study is instrumental in identifying the optimal OSA therapy for Veterans with PTSD and the OSA phenotype that would predict oral appliance response
Obstructive sleep apnea (OSA) is a prevalent disorder associated with poor neurocognitive performance and organ system dysfunction due to intermittent hypoxia and repeated arousals. The repetitive hemodynamic stresses are implicated in the increased incidence of systemic hypertension and cardiovascular diseases. Insufficient and disrupted sleep has similar negative impact on mood, attention, cognition, and behavior. In Veterans with post traumatic stress disorder (PTSD), the disturbed sleep can worsen further the cognitive-behavioral manifestations of PTSD and contributes to poor mental and physical health outcomes. Recent epidemiologic studies largely support the association of higher rates of OSA in patients with PTSD compared with the general population. Treatment of the underlying obstructive sleep disturbances with continuous positive airway pressure (CPAP) has resulted in restoration of sleep architecture, decrease daytime sleepiness, and reduction in nightmares frequency and intensity. However, adherence to treatment with CPAP is less than optimal in Veterans with PTSD. Mandibular advancing devices (MADs) are considered non surgical alternatives to CPAP and are preferred in a head to head comparison to CPAP in OSA subjects without PTSD. However, there has been no study to the investigators' knowledge that has assessed MAD in terms of clinical efficacy, compliance, and quality of sleep compared to CPAP in OSA patients with PTSD. Therefore, the investigators hypothesize that MAD is not inferior to CPAP in treating OSA effectively in Veterans with PTSD and OSA. To that end, the investigators propose to conduct a feasibility study using a randomized crossover trial of 12 weeks of CPAP and MAD in 42 consecutive outpatients with PTSD newly diagnosed with OSA separated by 2 weeks washout period.
The primary endpoint of the trial is to compare the treatment efficacy of CPAP and MAD in Veterans with PTSD and OSA. Secondary endpoints aim at: 1) comparing change in the Epworth Sleepiness Scale, SF-36, and the Pittsburgh Sleep Quality Index at end of treatment following use of CPAP versus MAD, 2) comparing adherence and short-term side effects between using CPAP and MAD in PTSD patients with OSA, and 3) determining anthropomorphic, polysomnographic, and cephalometric predictors of successful MDA response. Assessments at the end of both limbs comprise evaluation of quality of sleep, daytime sleepiness, quality of life, and side effects of treatment. Compliance with each therapy will be measured at the end of each treatment period.
The results of the trial are pivotal in determining the efficacy, tolerability, and adherence to MAD compared to CPAP in Veterans with PTSD and OSA. This feasibility study would form the basis of a future trial examining the effectiveness of various therapeutic modalities for OSA on PTSD symptomatology and progression.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CPAP First, MAD | Active Comparator | CPAP treatment for sleep apnea CPAP: CPAP Treatment for 12 weeks MAD: MAD treatment for 12 weeks |
|
| MAD First, CPAP | Experimental | MAD treatment for sleep apnea MAD: MAD Treatment for 12 weeks CPAP: CPAP treatment for 12 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CPAP | Device | CPAP Treatment for 12 weeks |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Residual Apnea Hypopnea Index | The primary endpoint of the study was tested by comparing the upper limit of the 95% confidence interval for the CPAP-MAD difference in residual AHI with the a priori noninferiority margin using the paired t test | up to 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Health Outcomes | Health outcomes including ESS, PCL-M, and PSQI. ESS is a short questionnaire validated to measure excessive daytime sleepiness in patients with OSA 17. It measures the likelihood of falling asleep in eight different situations, with a score of 0-3 for each situation. The sum of individual scores for the eight items gives the final ESS score, ranging from 0-21. An ESS score >10 suggests excessive daytime sleepiness (EDS). The PSQI is a self-rating questionnaire that consists of seven dimensions. The possible scores range from 0-21, with greater than five indicative of impaired sleep quality. The PTSD Checklist is a 17-item self-report measure (1-5 points each) that assesses PTSD symptoms in relation to stressful military experiences. PTSD symptom severity scores are determined by summing the participants' answers to all 17 items from 1 ("not at all") to 5 ("extremely")(range 17-85) 14 with 5-10 point change indicating statistically significant response to treatment |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ali A El-Solh, MD MPH | VA Western New York Healthcare System, Buffalo, NY | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| VA Western New York Healthcare System, Buffalo, NY | Buffalo | New York | 14215 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29065960 | Derived | El-Solh AA, Homish GG, Ditursi G, Lazarus J, Rao N, Adamo D, Kufel T. A Randomized Crossover Trial Evaluating Continuous Positive Airway Pressure Versus Mandibular Advancement Device on Health Outcomes in Veterans With Posttraumatic Stress Disorder. J Clin Sleep Med. 2017 Nov 15;13(11):1327-1335. doi: 10.5664/jcsm.6808. |
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A total of 127 Veterans were considered for study participation between August 2013 and April 2016. Fifty-four patients agreed to enroll in the study but twelve patients either failed to return for scheduled visits or withdrew from further participation because of lack of time or other pressing matters. Forty-two were randomized to CPAP or MAD.
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| ID | Title | Description |
|---|---|---|
| FG000 | CPAP First, MAD | CPAP treatment for sleep apnea CPAP: CPAP Treatment for 12 weeks MAD: MAD treatment for 12 weeks |
| FG001 | MAD First, CPAP | MAD treatment for sleep apnea MAD: MAD Treatment for 12 weeks CPAP: CPAP treatment for 12 weeks |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention |
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| ||||||||||||||||||
| Second Intervention |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | Participants were asked to acclimate to CPAP and MAD for 4 weeks (total) during which adjustments to both modes of therapy are made aiming to optimize comfort and abolish snoring. If the interface was found to be uncomfortable, the patient was given the opportunity to change the mask. None of the participants was exposed to dual therapy or had access to both devices at the same time. Weekly phone calls were made to inquire about side effects or problems with CPAP or MAD. At the end of the acclimatization period, patients underwent a 2-week washout, after which they were randomly assigned in 1:1 ratio via a presealed and numbered opaque white envelope to one of the two treatment modalities (CPAP or MAD) that included the assignment to receive 12 weeks of treatment with MAD and CPAP in alternating order |
| 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 | Residual Apnea Hypopnea Index | The primary endpoint of the study was tested by comparing the upper limit of the 95% confidence interval for the CPAP-MAD difference in residual AHI with the a priori noninferiority margin using the paired t test | Posted | Mean | Standard Deviation | events per hour | 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 | CPAP | CPAP treatment for sleep apnea CPAP: CPAP Treatment for 12 weeks |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| mask discomfort | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ali El Solh | VA Western New York | 716-862-6525 | ali.el-solh@va.gov |
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| ID | Term |
|---|---|
| D020181 | Sleep Apnea, Obstructive |
| D013313 | Stress Disorders, Post-Traumatic |
| ID | Term |
|---|---|
| D012891 | Sleep Apnea Syndromes |
| D001049 | Apnea |
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
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randomized trial
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| MAD |
| Device |
MAD Treatment for 12 weeks |
|
| 12 weeks |
| General Health SF-36 | The SF-36 is a generic 36-item Short Form Medical Outcomes Survey (SF-36) 16. It has eight main domains: physical functioning, role limitation due to physical problems, role limitation due to emotional problems, social functioning, mental health, energy/vitality, bodily pain, and general health perception. General Health SF36 score is coded, summed, and transformed onto a scale from 0 to 100 (worst to best possible health). | 12 weeks |
| Adherence to Therapy | comparison of the number of hours per night used while on CPAP versus MAD | 12 weeks |
| NOT COMPLETED |
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|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Units | Counts |
|---|
| Participants |
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|
|
| Secondary | Health Outcomes | Health outcomes including ESS, PCL-M, and PSQI. ESS is a short questionnaire validated to measure excessive daytime sleepiness in patients with OSA 17. It measures the likelihood of falling asleep in eight different situations, with a score of 0-3 for each situation. The sum of individual scores for the eight items gives the final ESS score, ranging from 0-21. An ESS score >10 suggests excessive daytime sleepiness (EDS). The PSQI is a self-rating questionnaire that consists of seven dimensions. The possible scores range from 0-21, with greater than five indicative of impaired sleep quality. The PTSD Checklist is a 17-item self-report measure (1-5 points each) that assesses PTSD symptoms in relation to stressful military experiences. PTSD symptom severity scores are determined by summing the participants' answers to all 17 items from 1 ("not at all") to 5 ("extremely")(range 17-85) 14 with 5-10 point change indicating statistically significant response to treatment | Posted | Mean | Standard Deviation | units on a scale | 12 weeks |
|
|
|
|
| Secondary | General Health SF-36 | The SF-36 is a generic 36-item Short Form Medical Outcomes Survey (SF-36) 16. It has eight main domains: physical functioning, role limitation due to physical problems, role limitation due to emotional problems, social functioning, mental health, energy/vitality, bodily pain, and general health perception. General Health SF36 score is coded, summed, and transformed onto a scale from 0 to 100 (worst to best possible health). | Posted | Mean | Standard Deviation | units on a scale | 12 weeks |
|
|
|
|
| Secondary | Adherence to Therapy | comparison of the number of hours per night used while on CPAP versus MAD | Posted | Mean | Standard Deviation | hours per night | 12 weeks |
|
|
|
|
| 0 |
| 35 |
| 26 |
| 35 |
| EG001 | Mandibular Advancing Device | MAD treatment for sleep apnea MAD: MAD Treatment for 12 weeks | 0 | 35 | 14 | 35 |
| claustrophobia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Jaw pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Dry mouth | General disorders | Systematic Assessment |
|
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| D020919 |
| Sleep Disorders, Intrinsic |
| D020920 | Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
| D040921 | Stress Disorders, Traumatic |
| D000068099 | Trauma and Stressor Related Disorders |
| D001523 | Mental Disorders |
| Pitt sleep quality index |
|
| 0.98 |
| Equivalence |
t test assuming unequal variance |
| PSQI | t-test, 2 sided | 0.31 | Equivalence | t-test assuming non unequal variance |