SchizophreniaPhase 2RADIAUSNCT01411085
Risperidone and Desipramine in Alcohol Use and Schizophrenia
A Phase 2 study testing Risperidone + Desipramine in people with Schizophrenia and Alcoholism, run by Dartmouth-Hitchcock Medical Center at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia, Alcoholism, Dual Diagnosis
- What is being tested?
- Risperidone + Desipramine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 4 sitesUnited States
- Study dates
- Dec 2011to Sep 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Meets the diagnostic criteria of schizophrenia or schizoaffective disorder
- Meets the diagnostic criteria for a current alcohol use disorder (abuse or dependence)
- Recent alcohol use as documented on the Timeline Followback
- Receives outpatient treatment with oral antipsychotic medication (including risperidone.
- Is willing to switch to risperidone treatment at the beginning of the study.
Who cannot join
- Other substance use disorder other than alcohol, caffeine and nicotine, and cannabis abuse, as defined by DSM-IV criteria.
- Receives current treatment with Clozapine
- Continues to use alcohol despite current adequate treatment with medication to decrease alcohol use(e.g. naltrexone, acamprosate, disulfiram or topiramate)
- Is determined to be a "slow metabolizer" of CYP2D6
- Is currently pregnant, trying to become pregnant, or nursing
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of South Carolina School of Medicine
Columbia, South Carolina, 29203
Michigan State University / Cherry Street Health Services
Grand Rapids, Michigan, 49503
Dartmouth Medical School
Lebanon, New Hampshire, 03756
University of Massachusetts Medical School
Worcester, Massachusetts, 01605
About this study
Official title: Alcoholism and Schizophrenia: A Translational Approach to Treatment
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:
- 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
- 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
- To assess the side effect burden associated with the combination of these two medications in participants.
Read more
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.
Read the 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.
- Conditions
- Schizophrenia, Alcoholism, Dual Diagnosis
- Being tested
- Risperidone + Desipramine
- Keywords
- Schizophrenia, Alcoholism, Dual Diagnosis, Desipramine, Risperidone
- Medical subject headings
- Schizophrenia, Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Risperidone + DesipramineDrug
Also called Norpramin
| Study group | Role | What they receive |
|---|---|---|
| Risperidone + Desipramine | Experimental | 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. Receives: Drug: Risperidone + Desipramine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Timeline Followback Assessing Number of Drinks Per Week
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.
Measured: Weekly for 14 weeks, using data from last 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2011 (estimated)
- Study startDec 2011
- Primary completionAug 2014
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Dartmouth-Hitchcock Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dartmouth-Hitchcock Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of South Carolina, University of Massachusetts, Worcester, Michigan State University
- Responsible party
- Principal investigator, Alan Green, Dartmouth-Hitchcock Medical Center
- Investigators
- Alan I Green, MD, Principal investigator, Dartmouth-Hitchcock Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01411085
- Sponsor's protocol ID
- 1R21AA019534-01A1
- Acronym
- RADIAUS
- Status last verified
- Mar 2018
- First submitted
- 16 Jun 2011
- Last updated
- 23 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Alcoholism and Schizophrenia: A Translational Approach to Treatment
- ClinicalTrials.gov ID
- NCT01411085
- Acronym / sponsor ID
- RADIAUS / 1R21AA019534-01A1
- Conditions
- Schizophrenia, Alcoholism, Dual Diagnosis
- Keywords
- Schizophrenia, Alcoholism, Dual Diagnosis, Desipramine, Risperidone
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Dartmouth-Hitchcock Medical CenterUniversity, hospital or other
- Collaborators
- University of South Carolina, University of Massachusetts, Worcester, Michigan State University
- Study start
- Dec 2011
- Primary completion
- Aug 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 8 Aug 2011 (estimated)
- Results
- Posted 23 Mar 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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
- 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
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Risperidone + Desipramine | Experimental | Drug: Risperidone + DesipramineAll 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Meets the diagnostic criteria of schizophrenia or schizoaffective disorder
- Meets the diagnostic criteria for a current alcohol use disorder (abuse or dependence)
- Recent alcohol use as documented on the Timeline Followback
- Receives outpatient treatment with oral antipsychotic medication (including risperidone.
- Is willing to switch to risperidone treatment at the beginning of the study.
Key exclusion criteria (5 listed)
- Other substance use disorder other than alcohol, caffeine and nicotine, and cannabis abuse, as defined by DSM-IV criteria.
- Receives current treatment with Clozapine
- Continues to use alcohol despite current adequate treatment with medication to decrease alcohol use(e.g. naltrexone, acamprosate, disulfiram or topiramate)
- Is determined to be a "slow metabolizer" of CYP2D6
- Is currently pregnant, trying to become pregnant, or nursing
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Risperidone + DesipramineAlso: Norpramin | Drug | Risperidone + Desipramine |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Schizophrenia
Recruiting
MI-CBTech: A Mobile Intervention for Community Integration in Homeless-Experienced Veterans With SMI
Schizophrenia Spectrum Disorders, Psychotic Affective Disorders
RecruitingObservational study
Tau Biomarkers in Late-onset Psychosis (LOP)
Late Onset Schizophrenia, Delusional Disorder (Late Onset)
Active, not recruitingObservational study
Profiling Vulnerability and Resilience for Mental Illness Following Viral Infections
Severe Mental Illness, Inflammation
RecruitingPhase 3
Sequential Treatment Approaches for Treatment-Resistant Schizophrenia
Treatment-resistant Schizophrenia
Recruiting
REACH Study (Recovery Environments: Assessing Cognitive & Brain Health in Community Mental Health)
Schizophrenia, Schizo Affective Disorder
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alan I Green, MD principal investigator
Dartmouth-Hitchcock Medical Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Risperidone + Desipramine in people with Schizophrenia and Alcoholism, run by Dartmouth-Hitchcock Medical Center at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Mar 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Timeline Followback Assessing Number of Drinks Per Week (time frame: Weekly for 14 weeks, using data from last 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2018.