Comparison of Quetiapine and Trazodone Treatment for Insomnia in Dually Diagnosed Veterans

NCT01662297 | Terminated Phase 4 Results DMC

• 2 other identifiers: Quetiapine-Trazodone InsomniaVA MIRB #01579
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot comparative effectiveness study designed to determine whether trazodone is as effective as quetiapine for treatment of insomnia in veterans with a history of addiction and mental health issues. The study will have two concurrent phases (parts); first an acceptability determination phase, to determine whether and why (or why not) veterans already taking quetiapine are willing to try an alternative to quetiapine for sleep; and second, a randomized trial phase which will test whether staying on quetiapine has any advantage over switching to trazodone. The purpose of the first phase will be a) to document the proportions of patients and physicians who are willing to agree to such a switch, b) to characterize sociodemographic and clinical characteristics of potentially eligible subjects associated with a willingness to switch from quetiapine to trazodone and c) to record the reasons given why patients and their prescribers are (or are not) willing to accept a switch from quetiapine to trazodone. It will also function to provide some educational background to patients and a reminder to providers about the potential severe side-effects of quetiapine, and will thus facilitate clinical informed consent for the clinical trial phase of the study. Completion of the first part of the study will also serve as the screening component for part II. Part II includes, first, obtaining written informed consent from eligible subjects, and then randomly assigning them to continue quetiapine or to be switched to trazodone in open-label "real world" fashion for the duration of 4 weeks, followed by another four weeks of open, non-randomized follow- up. The purpose of the second part of the study is to determine if trazodone is an adequate substitute for quetiapine, primarily in terms of treating insomnia. The investigators hypothesize that trazodone will not be inferior to quetiapine in maintaining good quality of sleep measured by sleep scales (i.e., scores will not significantly worsen once switched). This study is open to Veterans in the VA system only. Eligible subjects must have a history of "dual diagnosis" (i.e., a history of addiction and mental illness).

Conditions

Insomnia; Mental Health Disorder; Substance Use Disorder

Keywords

Quetiapine; Trazodone; Insomnia; Dual Diagnosis

Outcome Measures

Primary Outcomes (1)

• Change in Average Pittsburgh Sleep Quality Inventory (PSQI)Score

  Data analyzed for change from score at baseline, to week 4, to week 8. The range of scores is 0-21 on this scale, with higher scores indicating worse sleep quality. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. This is a comparison between groups (trazodone versus quetiapine)of the change on TOTAL PSQI scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The first four weeks of treatment is the active acute experiment phase, and this will be the main comparison time period for the endpoint, but the investigators will also analyze change in PSQI until the follow-up point at the end of week 8.

  From baseline (week 0) to end of 4 week and end of week 8

Secondary Outcomes (8)

• Change in Insomnia Severity Index (ISI) Scores

  from baseline (week 0) to the end of week 4 and at week 8

• Change in Epworth Sleepiness Scale (ESS) Over Time

  From baseline (week 0) to end of week 8

• Change in RAND Short Form 36 Item Health Survey (RAND-SF36) General Health Subscale Over Time

  from week 0 (baseline) to end of week 8

• Change in Brief Symptom Inventory (BSI) Over Time

  from week 0 (baseline) to end of week 8

• Change in Alcohol Urge Questionnaire (AUQ)Scores Over Time

  from week 0 (baseline) to end of week 8

Study Arms (2)

Quetiapine

ACTIVE COMPARATOR

Veterans remaining on quetiapine for insomnia.

Drug: Quetiapine

Trazodone

ACTIVE COMPARATOR

Veterans switching from quetiapine to trazodone for the treatment of insomnia.

Drug: Trazodone

Interventions

Quetiapine DRUG

Quetiapine will be administered at a dosage prescribed by veterans' current providers for the treatment of insomnia.

Also known as: Seroquel, Quetiapine Fumarate

Quetiapine

Trazodone DRUG

Veterans willing to switch from quetiapine to trazodone for the treatment of insomnia will receive up to 400mg of trazodone daily.

Also known as: Desyrel, Oleptro

Trazodone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Identified by their VA prescribing provider as taking quetiapine primarily as a sedative/hypnotic agent for some form of insomnia for at least 1 month
• Identified by their VA prescribing provider as having dual diagnosis; a lifetime history of substance use disorder and a mental disorder
• Willing to meet with a research assistant to answer several questions regarding their use of and experience with quetiapine.
• Willing to provide written informed consent.
• Provider reports that primary use of quetiapine is for insomnia for at least one month and not primary or augmentation treatment of mood, anxiety disorder, psychosis, or mood stabilization.
• Have a self-identified and provider confirmed lifetime history of mental health and substance use disorder (dual diagnosis).
• Currently taking Quetiapine up to 300mg daily for the primary purpose of treating insomnia, and have been taking it for at least 1 month (30 days).
• Use of an acceptable method of birth control by female patients who have a possibility of becoming pregnant.
• The provider should review the patients from the identified charts, and fill out information about the patient and why they are on the drug, and provider should consent to us approaching the client and potentially switching them; the investigators will not approach and begin enrollment for part II on subjects if their provider feels it is not appropriate for them for any reason.
• Concomitant administration of: other sedative hypnotics, benzodiazepines, prazosin, other atypical antipsychotics, stimulants, ketoconazole and other inhibitors of cytochrome P450 3A (e.g., itraconazole, fluconazole, erythromycin, and protease inhibitors), phenytoin or other strong inducers of cytochrome P450 enzymes.
• Intolerance or hypersensitivity to trazodone.
• Pregnant or lactating women or women planning to become pregnant.
• Hepatic or renal problems AST or ALT (\>3 times upper limit of normal);
• Elevated bilirubin (\>1.2), BUN (\>24), creatinine (\>1.7).
• Unstable, serious medical condition or one requiring acute medical treatment, or anticipation of hospitalization for extended care.

Sponsors & Collaborators

• VA Connecticut Healthcare System: lead

Study Sites (1)

VA Connecticut Healthcare System

West Haven, Connecticut, 06516, United States

Location

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders; Mental Disorders; Substance-Related Disorders

Interventions

Quetiapine Fumarate; Trazodone

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Dibenzothiazepines; Thiazepines; Thiepins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Pyridones; Pyridines

Results Point of Contact

• Title: Dr. Albert Arias
• Organization: Yale University/West Haven VAMC

albert.arias@va.gov

2039325711

Study Officials

• Albert J Arias, MD, MS

  Yale University/Veterans Affairs CT

  PRINCIPAL INVESTIGATOR

• Elizabeth Ralevski, Ph.D.

  Yale University/Veterans Affairs CT

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2012
• First Posted: August 10, 2012
• Study Start: July 1, 2012
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: October 16, 2018
• Results First Posted: October 16, 2018

Record last verified: 2018-10

Locations

US (1)