Clinical trial NCT03265951: Ramelteon for Complex Insomnia in Veterans With PTSD
Official title: A Pilot, Randomized, Double-blind, Placebo Controlled, Trial of Ramelteon for CPAP Non-Adherent Veterans With PTSD and Complex Insomnia
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Insomnia
Keywords: sleep apnea, PTSD
Lead sponsor: State University of New York at Buffalo
Sponsor class: OTHER
Collaborators: name: The VA Western New York Healthcare System
First posted: 2017-08-29
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Pittsburgh Sleep Quality Index
timeFrame: 12 weeks post randomization
Secondary outcomes:
measure: PCL-5
timeFrame: 12 weeks post randomization
measure: ISI
timeFrame: 12 weeks post randomization
measure: CPAP adherence
timeFrame: 12 weeks post randomization
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Veterans Affairs Medical Center in Buffalo
state: New York
Study officials:
affiliation: The VA Western New York
name: Ali El Solh, MD
role: PRINCIPAL_INVESTIGATOR
References: