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

A Randomized Cross Over Trial of Two Treatments for OSA in Veterans With PTSD

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

Study Overview

• Status: Completed
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: 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 Type: Interventional
• Enrollment (Actual): 42
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14215
      • VA Western New York Healthcare System, Buffalo, NY

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: VA Office of Research and Development

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2012
• Primary Completion (ACTUAL): October 30, 2016
• Study Completion (ACTUAL): March 30, 2017

Study Registration Dates

• First Submitted: March 20, 2012
• First Submitted That Met QC Criteria: March 29, 2012
• First Posted (ESTIMATE): April 2, 2012

Study Record Updates

• Last Update Posted (ACTUAL): November 8, 2017
• Last Update Submitted That Met QC Criteria: November 3, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: continuous positive airway pressure; oral appliance; post traumatic stress disorder
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
• Other Study ID Numbers: CLIN-005-11F

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No