Risperidone and Desipramine in Alcohol Use and Schizophrenia (RADIAUS)

This study is currently recruiting participants.
Verified October 2013 by Dartmouth-Hitchcock Medical Center
Sponsor:
Collaborators:
University of South Carolina
University of Massachusetts, Worcester
Michigan State University
Information provided by (Responsible Party):
Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier:
NCT01411085
First received: June 16, 2011
Last updated: October 25, 2013
Last verified: October 2013
  Purpose

The purpose of this study is to determine whether participants who are treated with risperidone in combination with desipramine have less alcohol use (fewer drinking days; fewer heavy drinking days) than do participants who are treated with RISP with placebo. The primary hypothesis is that compared to treatment with risperidone, participants randomized to a combination of risperidone plus desipramine will have fewer days of drinking, as well as fewer days of heavy drinking. The study will also compare the effects of risperidone as compared to risperidone plus desipramine on participants' symptoms and side effects.


Condition Intervention Phase
Schizophrenia
Alcoholism
Dual Diagnosis
Drug: Risperidone + Desipramine
Drug: Risperidone + Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Alcoholism and Schizophrenia: A Translational Approach to Treatment

Resource links provided by NLM:


Further study details as provided by Dartmouth-Hitchcock Medical Center:

Primary Outcome Measures:
  • Timeline Followback [ Time Frame: Weekly for 14 weeks ] [ Designated as safety issue: No ]
    Alcohol/other substance use (including tobacco) will be assessed primarily by weekly self-report using the Timeline Followback (TLFB) method enhanced by procedures to strengthen the reliability and validity of this measure. Our data and Carey's suggest that the TLFB is useful for assessing alcohol use in persons diagnosed with SCZ. We will use well delineated procedures to minimize response bias,e.g., and we will obtain a Certificate of Confidentiality. The self-report data will be buttressed with other data.


Estimated Enrollment: 40
Study Start Date: December 2011
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Risperidone + Desipramine
All participants will be treated with risperidone at the time of randomization. Participants randomized to receive placebo will continue to receive risperidone plus a encapsulated desipramine.
Drug: Risperidone + Desipramine
At the time of randomization all participants will already be treated with a target does of 4 mg of risperidone. Participants randomized to receive risperidone plus desipramine will receive double blind desipramine. The target dose is 100mg.
Other Name: Norpramin
Active Comparator: Risperidone + Placebo
All participants will be treated with risperidone at the time of randomization. Participants randomized to receive placebo will continue to receive risperidone plus a placebo capsule identical to the encapsulated desipramine.
Drug: Risperidone + Placebo
At the time of randomization all participants will already be treated with a target does of 4 mg of risperidone. Participants randomized to receive risperidone + placebo will receive a placebo capsule identical to the encapsulated desipramine.

Detailed Description:

Alcohol use disorder (AUD) is at least three times more common in schizophrenia (SCZ) than in the general population, and worsens the course of SCZ. Typical antipsychotic agents are of limited value in controlling alcohol use in these "dual diagnosis" patients. Data from our group and others suggest that the atypical antipsychotic drug clozapine (CLOZ) limits alcohol and cannabis use in "dual diagnosis" patients with SCZ much more effectively than other antipsychotics that have been assessed, however, the side effects produced by CLOZ severely limit its use.

The investigators have hypothesized that CLOZ will lessen alcohol/substance use in such dual diagnosis patients in part because of its mechanism of action that includes release of dopamine (DA) in the prefrontal cortex which will help to normalize dysfunctional brain reward circuits that may underlie the co- occurring alcohol/substance use in patients with schizophrenia. Our data suggest that the effect of CLOZ can be duplicated in rodents when medications with CLOZ-like activity (DA D2 antagonism, potent norepinephrine (NE) α2 receptor antagonism and NE reuptake inhibition) are combined together. The investigators have demonstrated that RISP (a medication that is both a DA D2 receptor antagonist, and a potent NE α2 receptor antagonist), in combination with the specific NE reuptake inhibitor desipramine (DMI), significantly decreases alcohol consumption in alcohol drinking rodents.

This translational study is a pilot "proof of concept" 14-week double-blind investigation of 40 participants who have co-occurring diagnoses of SCZ and AUD. Patients not treated with RISP at the time of consent will be switched to RISP in the first two weeks of the study. At Week 3, all participants will be randomized to treatment with risperidone (RISP) with placebo or RISP plus desipramine (DMI) and followed for 12 weeks. The primary outcome measure will be days of drinking (per week), as well as days of heavy drinking (per week). Exploratory aims will assess whether the addition of DMI alters symptoms (of SCZ and of depression), and increases side effects as compared to treatment with RISP and placebo. The investigators anticipate that data from this study will support a larger trial of RISP + DMI in patients with SCZ and AUD.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Meets the diagnostic criteria of schizophrenia or schizoaffective disorder
  2. Meets the diagnostic criteria for a current alcohol use disorder (abuse or dependence)
  3. Recent alcohol use as documented on the Timeline Followback
  4. Receives outpatient treatment with oral antipsychotic medication (including risperidone.
  5. Is willing to switch to risperidone treatment at the beginning of the study.

Exclusion Criteria:

  1. Other substance use disorder other than alcohol, caffeine and nicotine, and cannabis abuse, as defined by DSM-IV criteria.
  2. Receives current treatment with Clozapine
  3. Continues to use alcohol despite current adequate treatment with medication to decrease alcohol use(e.g. naltrexone, acamprosate, disulfiram or topiramate)
  4. Is determined to be a "slow metabolizer" of CYP2D6
  5. Is currently pregnant, trying to become pregnant, or nursing
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01411085

Contacts
Contact: Christopher OKeefe, MA 603-271-5287 chris.okeefe@dartmouth.edu

Locations
United States, Massachusetts
University of Massachusetts Medical School Recruiting
Worcester, Massachusetts, United States, 01605
Contact: Matthew Goodnow    508-856-2494    Matthew.Goodnow@umassmed.edu   
Principal Investigator: Xiaoduo Fan, MD         
United States, Michigan
Michigan State University / Cherry Street Health Services Recruiting
Grand Rapids, Michigan, United States, 49503
Contact: Heather Willet    616-695-8200 ext 7168    heatherwillet@cherryhealth.com   
Principal Investigator: Eric Achtyes, M.D.         
United States, New Hampshire
Dartmouth Medical School Recruiting
Lebanon, New Hampshire, United States, 03756
Contact: Christopher OKeefe, MA    603-271-5287    chris.okeefe@dartmouth.edu   
Principal Investigator: Alan Green, MD         
United States, South Carolina
University of South Carolina School of Medicine Not yet recruiting
Columbia, South Carolina, United States, 29203
Contact: Suzanne Hardeman, MRC, MSN, LPC, PMHNP-BC    803-434-3622    Suzanne.Hardeman@uscmed.sc.edu   
Principal Investigator: Meera Narasimhan, MD         
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
University of South Carolina
University of Massachusetts, Worcester
Michigan State University
Investigators
Principal Investigator: Alan I Green, MD Dartmouth-Hitchcock Medical Center
  More Information

No publications provided

Responsible Party: Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT01411085     History of Changes
Other Study ID Numbers: 1R21AA019534-01A1
Study First Received: June 16, 2011
Last Updated: October 25, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Dartmouth-Hitchcock Medical Center:
Schizophrenia
Alcoholism
Dual Diagnosis
Desipramine
Risperidone

Additional relevant MeSH terms:
Alcoholism
Schizophrenia
Alcohol-Related Disorders
Substance-Related Disorders
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Desipramine
Risperidone
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antidepressive Agents, Tricyclic
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Adrenergic Uptake Inhibitors
Adrenergic Agents
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs
Serotonin Antagonists
Serotonin Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Dopamine Antagonists
Dopamine Agents

ClinicalTrials.gov processed this record on April 21, 2014