Risperidone and Desipramine in Alcohol Use and Schizophrenia (RADIAUS)
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.
Drug: Risperidone + Desipramine
Drug: Risperidone + Placebo
|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|
- 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.
|Study Start Date:||December 2011|
|Estimated Study Completion Date:||June 2014|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
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.
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.
|Contact: Christopher OKeefe, MAfirstname.lastname@example.org|
|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 email@example.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 firstname.lastname@example.org|
|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|
|Principal Investigator:||Alan I Green, MD||Dartmouth-Hitchcock Medical Center|