Risperidone and Desipramine in Alcohol Use and Schizophrenia (RADIAUS)

This study is ongoing, but not recruiting participants.
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: June 13, 2014
Last verified: June 2014
  Purpose

Note: In June 2013, the study design was changed from a randomized controlled study of risperidone + despiramine vs. risperidone vs. placebo to an open label pre-post study of risperidone (or risperidone-like drug) + desipramine. The aims of the study were revised to read:

  1. To determine whether participants treated with risperidone in combination with desiprmaine have less alcohol use (fewer drinking days; fewer heavy drinking days) during the final 8 weeks on these medications as compared to pre-baseline. The primary hypothesis is that compared to pre-baseline, participants will demonstrate fewer days of drinking (per week), as well as fewer days of heavy drinking (per week) in the final eight weeks they are taking risperidone and desipramine, as recorded on the Timeline Follow-Back assessment
  2. To explore changes in symptoms (of schizophrenia and of depression) in the final eight weeks of treatment with risperidone + desipramine compared to the period before baseline
  3. To assess the side effect burden associated with the combination of these two medications in participants.

The original aims of the study were:

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
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
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: December 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Risperidone + Desipramine
All participants will be treated with risperidone (or a risperidone-like agent including: risperidone long-acting, paliperdione, and paliperidone palmitate) at the time treatment with desipramine is initiated. The target dose of oral risperidone is 4mg though variations are allowed. The target dose of desipramine is 100mg.
Drug: Risperidone + Desipramine
Other Name: Norpramin

Detailed Description:

Alcohol use disorder is at least three times more common in schizophrenia than in the general population, and worsens the course of schizophrenia. 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 limits alcohol and cannabis use in "dual diagnosis" patients with schizophrenia much more effectively than other antipsychotics that have been assessed, however, the side effects produced by clozapine severely limit its use.

The investigators have hypothesized that clozapine 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 clozapine can be duplicated in rodents when medications with clozapine-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, 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 schizophrenia and an alcohol use disorder. Patients not treated with risperidone (or a risperidone-like agent, including risperidone long-acting, paliperidone and paliperidone palmitate) at the time of consent will be switched to oral risperidone in the first two weeks of the study. At Week 3, all participants will begin treatment with risperidone risperidone plus desipramine 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). The investigators anticipate that data from this study will support a larger trial of risperidone + desipramine in patients with schizophrenia and an alcohol use disorder.

  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
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: NCT01411085

Locations
United States, Massachusetts
University of Massachusetts Medical School
Worcester, Massachusetts, United States, 01605
United States, Michigan
Michigan State University / Cherry Street Health Services
Grand Rapids, Michigan, United States, 49503
United States, New Hampshire
Dartmouth Medical School
Lebanon, New Hampshire, United States, 03756
United States, South Carolina
University of South Carolina School of Medicine
Columbia, South Carolina, United States, 29203
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: June 13, 2014
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
Chemically-Induced Disorders
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Desipramine
Risperidone
Antidepressive Agents, Tricyclic
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
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 August 27, 2014