Ramelteon for Complex Insomnia in Veterans With PTSD

Study Overview
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Brief Summary
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Obstructive sleep apnea is commonly reported in Veterans with post-traumatic stress disorder, which can potentiate symptoms of anxiety and depression, daytime symptoms and worsen nightmares. Continuous positive airway pressure is the most effective therapy but adherence to treatment is suboptimal. The overarching theme of the proposal is to compare usual care to Ramelteon, in a randomized, clinical trial, investigating the effectiveness of physiological versus pharmacological intervention on sleep quality of life, insomnia severity and CPAP adherence.

Detailed Description
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Despite the overall improvement in PTSD symptomatology with CPAP therapy, adherence to CPAP is far worse in Veterans with PTSD (41%) compared to the general population with OSA (70%). Among the factors associated with CPAP non-adherence is the coexistence of insomnia. Complex insomnia defined as the coexistence of comorbid insomnia ans OSA is a frequent diagnosis in military personnel with combat exposure. Similar to prior reports of patients with OSA without PTSD, comorbid insomnia can create a barrier to CPAP therapy. Ramelteon (TAK-375), approved by the Food and Drug Administration for the treatment of insomnia with sleep onset abnormalities, is a neurohormone that functions as a melatonin receptor agonist targeting the MT1 and MT2 receptors located in the suprachiasmatic nucleus of the hypothalamus which regulates the circadian rhythm of the 24-hour sleep-wake cycle.The goal is to test the hypothesis that the administration of insomnia therapy-ramelteon- significantly improves treatment outcomes in Veterans with PTSD and complex insomnia compared with placebo.

Official Title
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A Pilot, Randomized, Double-blind, Placebo Controlled, Trial of Ramelteon for CPAP Non-Adherent Veterans With PTSD and Complex Insomnia

Conditions
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Insomnia

Intervention / Treatment
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* Drug: Ramelteon
* Other: Usual Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years and ≤70 years old Diagnosis of PTSD as determined by the intake conducted through the PTSD Clinic or the Mental Health Clinic Documented obstructive sleep apnea by polysomnography (AHI≥5 or more/hour) CPAP non adherence defined as less than 70% of nights with >4h CPAP use despite addressing modifiable barriers for CPAP adherence Psychotherapeutic treatment stable for at least 4 weeks prior to randomization Capable of giving informed consent Exclusion Criteria: Medical: Acute or unstable chronic medical illness History of narcolepsy and/or cataplexy Use of any of these medications: Fluvoxamine, fluconazole (Diflucan), itraconazole (Sporanox), and ketoconazole (Nizoral); cimetidine (Tagamet); clarithromycin (Biaxin); fluoroquinolones including ciprofloxacin, levofloxacin (Levaquin), moxifloxacin (Avelox), norfloxacin (Noroxin), ofloxacin (Floxin), others; HIV protease inhibitors including indinavir (Crixivan), nelfinavir (Viracept), and ritonavir (Norvir, in Kaletra); nefazodone; rifampin Treatment for seizure disorders Pregnant or lactating History of clinically significant hepatic impairment History of hypersensitivity, intolerance, or contraindication to ramelteon Unwilling to try or use CPAP Psychiatric/Behavioral: Diagnosis of current schizophrenia or schizoaffective disorder Diagnosis of a substance dependence/abuse disorder in the past year Severe psychiatric instability or severe situational life crises, including evidence of being actively suicidal or homicidal, or any behavior which poses an immediate danger to patient or others Diagnosis of bipolar disorder Consumption of more than two alcoholic beverages per night Receiving behavioral or pharmacological treatment for insomnia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ramelteon<br>Ramelteon 8 mg po at bedtime | Drug: Ramelteon<br>* 8 mg once daily administered within 30 minutes of bedtime<br>* Other names: Rozerem;|
| Placebo Comparator: Usual care<br>education brochure about sleep hygiene | Other: Usual Care<br>* education brochure about sleep hygiene<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pittsburgh Sleep Quality Index | Quality of life | 12 weeks post randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PCL-5 | PTSD Checklist | 12 weeks post randomization | 
| ISI | Insomnia Severity Index | 12 weeks post randomization | 
| CPAP adherence | CPAP adherence | 12 weeks post randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sleep apnea, PTSD