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A Randomized Cross Over Trial of Two Treatments for Sleep Apnea in Veterans With Post-Traumatic Stress Disorder

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ClinicalTrials.gov Identifier: NCT01569022
Recruitment Status : Completed
First Posted : April 2, 2012
Results First Posted : November 8, 2017
Last Update Posted : November 8, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:
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

Condition or disease Intervention/treatment
Obstructive Sleep Apnea Device: CPAP Device: MAD

Detailed Description:

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.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: randomized trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Cross Over Trial of Two Treatments for OSA in Veterans With PTSD
Actual Study Start Date : November 1, 2012
Primary Completion Date : October 30, 2016
Study Completion Date : March 30, 2017

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Active Comparator: CPAP First, MAD

CPAP treatment for sleep apnea

CPAP: CPAP Treatment for 12 weeks MAD: MAD treatment for 12 weeks

Device: CPAP
CPAP Treatment for 12 weeks
Device: MAD
MAD Treatment for 12 weeks
Experimental: MAD First, CPAP

MAD treatment for sleep apnea

MAD: MAD Treatment for 12 weeks CPAP: CPAP treatment for 12 weeks

Device: CPAP
CPAP Treatment for 12 weeks
Device: MAD
MAD Treatment for 12 weeks

Outcome Measures

Primary Outcome Measures :
  1. Residual Apnea Hypopnea Index [ Time Frame: up to 12 weeks ]
    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

Secondary Outcome Measures :
  1. Health Outcomes [ Time Frame: 12 weeks ]
    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

  2. General Health SF-36 [ Time Frame: 12 weeks ]
    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).

  3. Adherence to Therapy [ Time Frame: 12 weeks ]
    comparison of the number of hours per night used while on CPAP versus MAD

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Consecutive patients aged 18-70 years of age
  • Documented obstructive sleep apnea by polysomnography (AHI 5 or more/hr)
  • Established diagnosis of PTSD related to any past lifetime traumatic event and have a diagnosis of current, chronic PTSD

Exclusion Criteria:

  • Central sleep apnea defined as central apnea/hypopnea >50% of the total respiratory events
  • Prior treatment for sleep apnea
  • Veterans with fewer than 4 teeth remaining in either arch
  • Coexisting narcolepsy
  • Tempo-mandibular joint disease
  • Epilepsy
  • Prominent suicidal or homicidal ideation
  • Diagnosis of dementia
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01569022

United States, New York
VA Western New York Healthcare System, Buffalo, NY
Buffalo, New York, United States, 14215
Sponsors and Collaborators
VA Office of Research and Development
Principal Investigator: Ali A El-Solh, MD MPH VA Western New York Healthcare System, Buffalo, NY
More Information

Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT01569022     History of Changes
Other Study ID Numbers: CLIN-005-11F
First Posted: April 2, 2012    Key Record Dates
Results First Posted: November 8, 2017
Last Update Posted: November 8, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by VA Office of Research and Development:
post traumatic stress disorder
continuous positive airway pressure
oral appliance

Additional relevant MeSH terms:
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Stress Disorders, Traumatic
Stress Disorders, Post-Traumatic
Respiration Disorders
Respiratory Tract Diseases
Sleep Disorders, Intrinsic
Sleep Wake Disorders
Nervous System Diseases
Trauma and Stressor Related Disorders
Mental Disorders