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

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
VA Connecticut Healthcare System
ClinicalTrials.gov Identifier:
NCT01662297
First received: July 16, 2012
Last updated: August 10, 2012
Last verified: August 2012
  Purpose

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).


Condition Intervention Phase
Insomnia
Mental Health Disorder
Substance Use Disorder
Drug: Quetiapine
Drug: Trazodone
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Comparison of Quetiapine and Trazodone Treatment for Insomnia in Dually Diagnosed Veterans: an Open (e.g. Unblinded) Randomized Stay-Switch Pilot Trial

Resource links provided by NLM:


Further study details as provided by VA Connecticut Healthcare System:

Primary Outcome Measures:
  • Change in average Pittsburgh Sleep Quality Inventory (PSQI)score [ Time Frame: From baseline (week 0) to end of 8 week ] [ Designated as safety issue: No ]
    Measurements made at baseline, week 2, week 4, week 8. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. The change from week 4 to week 8 (post-intervention) will also be measured and analyzed, reported. This is a comparison between groups (trazodone versus quetiapine)of the change on 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.


Secondary Outcome Measures:
  • Change in Medical Outcomes Study Sleep Scale (MOS-SS)over time [ Time Frame: from baseline (week 0) to the end of week 8 ] [ Designated as safety issue: No ]
    Measurements made and reported at baseline, week 2, week 4, week 8. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. The change from week 4 to week 8 (post-intervention) will also be measured and analyzed, reported. This is a comparison between groups (trazodone versus quetiapine)of the change on MOS-SS 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 investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).

  • Change in Epworth Sleepiness Scale (ESS) over time [ Time Frame: From baseline (week 0) to end of week 8 ] [ Designated as safety issue: No ]
    Measurements made at baseline, week 2, week 4, week 8. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. The change from week 4 to week 8 (post-intervention) will also be measured and analyzed, reported. This is a comparison between groups (trazodone versus quetiapine)of the change on ESS 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 investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).

  • Change in RAND Short Form 36 Item Health Survey (RAND-SF36) over time [ Time Frame: from week 0 (baseline) to end of week 8 ] [ Designated as safety issue: No ]
    Measurements made at baseline, week 2, week 4, week 8. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. The change from week 4 to week 8 (post-intervention) will also be measured and analyzed, reported. This is a comparison between groups (trazodone versus quetiapine)of the change on RAND-SF36 scores over time. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).

  • Change in Brief Symptom Inventory (BSI)over time [ Time Frame: from week 0 (baseline) to end of week 8 ] [ Designated as safety issue: No ]
    Measurements made at baseline, week 2, week 4, week 8. 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 BSI 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 investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).

  • Change in Alcohol Urge Questionnaire (AUQ)scores over time [ Time Frame: from week 0 (baseline) to end of week 8 ] [ Designated as safety issue: No ]
    Measurements made at baseline, week 2, week 4, week 8. 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 AUQ scores over time. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).

  • Percentage of heavy drinking days [ Time Frame: from week 0 (baseline) to end of week 8 ] [ Designated as safety issue: No ]
    This is a comparison between groups of the mean percent heavy drinking days during the first 4 weeks, and then through to the follow up point (end of week 8). The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).

  • Percentage of negative urine drug screens [ Time Frame: from week 0 (baseline) to end of week 8 ] [ Designated as safety issue: No ]
    This is a comparison between groups of the mean percent of negative urine drug screens. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).


Estimated Enrollment: 122
Study Start Date: July 2012
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Quetiapine
Veterans remaining on quetiapine for insomnia.
Drug: Quetiapine
Quetiapine will be administered at a dosage prescribed by veterans' current providers for the treatment of insomnia.
Other Names:
  • Seroquel
  • Quetiapine Fumarate
Active Comparator: Trazodone
Veterans switching from quetiapine to trazodone for the treatment of insomnia.
Drug: Trazodone
Veterans willing to switch from quetiapine to trazodone for the treatment of insomnia will receive up to 400mg of trazodone daily.
Other Names:
  • Desyrel
  • Oleptro

Detailed Description:

Part I of the study involves identification through VA records of subjects eligible for the study based on their prescription of quetiapine. Potentially eligible subjects will be contacted by the research team. Subjects will answer a brief questionnaire about their experience with the medication quetiapine as used for insomnia. If subjects are interested in participated in part II, the clinical trial portion of the study, they will be further screened for eligibility.

Part II consists of a 4 week clinical trial in which subjects are randomized to stay on quetiapine or switch to trazodone, all of which will be open-label. Subjects will be evaluated for symptoms of sleep quality and excessive daytime sleepiness. subjects will also be assessed for changes in mood, and alcohol/drug use. After the initial 4 week treatment period, subjects on trazodone can choose to switch back to quetiapine or continue on trazodone. Subjects will also be evaluated after an additional 4 weeks (8weeks from start of the study) on outcome measures.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion/Exclusion Criteria (PHASE 1):

  • 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.
  • Appear not to be regularly on any medication which would be an exclusion for Part II (see Part II exclusion criteria).

Inclusion Criteria (PHASE 2):

  • 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.

Exclusion Criteria (PHASE 2):

  • Physiologic substance dependence requiring detoxification in the past 30 days (substance abuse is not an exclusion).
  • 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.
  • Dementia, epilepsy, insulin-dependent diabetes, anticoagulation with coumadin.
  • Legal entanglements or pending legal charges with potential of incarceration.
  • Recent (i.e., past 3 months) assault or suicide gesture currently needing acute intervention.
  • Concurrent participation in another clinical trial with an investigational drug during the last 30 days.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01662297

Locations
United States, Connecticut
VA Connecticut Healthcare System
West Haven, Connecticut, United States, 06516
Sponsors and Collaborators
VA Connecticut Healthcare System
Investigators
Principal Investigator: Albert J Arias, MD, MS Yale University/Veterans Affairs CT
Study Director: Elizabeth Ralevski, Ph.D. Yale University/Veterans Affairs CT
  More Information

No publications provided

Responsible Party: VA Connecticut Healthcare System
ClinicalTrials.gov Identifier: NCT01662297     History of Changes
Other Study ID Numbers: Quetiapine-Trazodone Insomnia, VA MIRB #01579
Study First Received: July 16, 2012
Last Updated: August 10, 2012
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by VA Connecticut Healthcare System:
Quetiapine
Trazodone
Insomnia
Dual Diagnosis

Additional relevant MeSH terms:
Mental Disorders
Substance-Related Disorders
Sleep Initiation and Maintenance Disorders
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Disorders
Nervous System Diseases
Trazodone
Quetiapine
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Antidepressive Agents, Second-Generation
Antidepressive Agents
Antipsychotic Agents

ClinicalTrials.gov processed this record on July 29, 2014