Ramelteon for Complex Insomnia in Veterans With PTSD (DORMI)

University at Buffalo (UB)

Status and phase

Withdrawn

Phase 4

Conditions

Insomnia

Treatments

Other: Usual Care

Drug: Ramelteon

Study type

Interventional

Funder types

Other

Other U.S. Federal agency

Identifiers

NCT03265951

RF-1070471

Details and patient eligibility

About

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.

Full 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.

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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