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Trial record 11 of 47 for:    DESIPRAMINE

Risperidone and Desipramine in Alcohol Use and Schizophrenia (RADIAUS)

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ClinicalTrials.gov Identifier: NCT01411085
Recruitment Status : Completed
First Posted : August 8, 2011
Results First Posted : March 23, 2018
Last Update Posted : March 23, 2018
Sponsor:
Collaborators:
University of South Carolina
University of Massachusetts, Worcester
Michigan State University
Information provided by (Responsible Party):
Alan Green, Dartmouth-Hitchcock Medical Center

Tracking Information
First Submitted Date  ICMJE June 16, 2011
First Posted Date  ICMJE August 8, 2011
Results First Submitted Date  ICMJE February 22, 2017
Results First Posted Date  ICMJE March 23, 2018
Last Update Posted Date March 23, 2018
Study Start Date  ICMJE December 2011
Actual Primary Completion Date August 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 21, 2018)
Timeline Followback Assessing Number of Drinks Per Week [ Time Frame: Weekly for 14 weeks, using data from last 8 weeks ]
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. It involves asking participants to retrospectively estimate their alcohol and other substance use.
Original Primary Outcome Measures  ICMJE
 (submitted: August 4, 2011)
Timeline Followback [ Time Frame: Weekly for 14 weeks ]
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.
Change History Complete list of historical versions of study NCT01411085 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Risperidone and Desipramine in Alcohol Use and Schizophrenia
Official Title  ICMJE Alcoholism and Schizophrenia: A Translational Approach to Treatment
Brief Summary

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.

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 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Schizophrenia
  • Alcoholism
  • Dual Diagnosis
Intervention  ICMJE Drug: Risperidone + Desipramine
Other Name: Norpramin
Study Arms  ICMJE 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.
Intervention: Drug: Risperidone + Desipramine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 17, 2015)
12
Original Estimated Enrollment  ICMJE
 (submitted: August 4, 2011)
40
Actual Study Completion Date  ICMJE September 2014
Actual Primary Completion Date August 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01411085
Other Study ID Numbers  ICMJE 1R21AA019534-01A1( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Alan Green, Dartmouth-Hitchcock Medical Center
Study Sponsor  ICMJE Dartmouth-Hitchcock Medical Center
Collaborators  ICMJE
  • University of South Carolina
  • University of Massachusetts, Worcester
  • Michigan State University
Investigators  ICMJE
Principal Investigator: Alan I Green, MD Dartmouth-Hitchcock Medical Center
PRS Account Dartmouth-Hitchcock Medical Center
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP