Ramelteon for Complex Insomnia in Veterans With PTSD (DORMI)

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Insomnia
• Intervention / Treatment: Drug: Ramelteon; Other: Usual Care

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.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14215
      • Veterans Affairs Medical Center in Buffalo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: State University of New York at Buffalo
• Collaborators: The VA Western New York Healthcare System
• Investigators: Principal Investigator: Ali El Solh, MD, The VA Western New York

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Actual): September 30, 2019
• Study Completion (Actual): June 30, 2020

Study Registration Dates

• First Submitted: August 25, 2017
• First Submitted That Met QC Criteria: August 25, 2017
• First Posted (Actual): August 29, 2017

Study Record Updates

• Last Update Posted (Actual): April 9, 2021
• Last Update Submitted That Met QC Criteria: April 8, 2021
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: sleep apnea, PTSD
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Initiation and Maintenance Disorders
• Other Study ID Numbers: RF-1070471

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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