SchizophreniaPhase 4CLOCSNCT01639872
Clozapine for Cannabis Use in Schizophrenia
A Phase 4 study testing Clozapine and Risperidone in people with Schizophrenia and Cannabis Abuse, run by Dartmouth-Hitchcock Medical Center at 9 sites in United States.
Trial summary
Many individuals with schizophrenia also suffer from marijuana addiction that worsens their problems related to schizophrenia. Most of the medications prescribed for schizophrenia have no effect on reducing marijuana use. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Schizophrenia, Cannabis Abuse, Cannabis Dependence
- What is being tested?
- Clozapine and Risperidone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 9 sitesUnited States
- Study dates
- 1 May 2013to 29 Mar 2017
- Phase
- Phase 4
- 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 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Clinical diagnosis of schizophrenia
- Clinical diagnosis of a cannabis use disorder (abuse or dependence)
Who cannot join
- Pregnant,trying to become pregnant or nursing
- History of a seizure disorder
- Current treatment with clozapine or risperidone
- Contraindication to treatment with clozapine or risperidone
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
University of South Carolina
Columbia, South Carolina, 29203
CNS Network Inc
Garden Grove, California, 92845
Michigan State University / Cherry Street Health Services
Grand Rapids, Michigan, 49503
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756
University of Miami
Miami, Florida, 33136
Pacific Research Partners
Oakland, California, 94607
University of North Carolina/UNC Center for Excellence in Community Mental Health
Raleigh, North Carolina, 27610
Rutland Regional Medical Center
Rutland, Vermont, 05701
Unversity of Massachusetts Medical School
Worcester, Massachusetts, 01605
About this study
Official title: Clozapine for Cannabis Use Disorder in Schizophrenia
Many individuals with schizophrenia also suffer from marijuana addiction that worsens their problems related to schizophrenia. Most of the medications prescribed for schizophrenia have no effect on reducing marijuana use. Preliminary data suggests that clozapine, an atypical antipsychotic, may limit marijuana use in people diagnosed with schizophrenia, but it is not commonly used due to its side effects and is reserved for people who do not respond to other antipsychotic medications.
In the proposed study, 132 individuals who are diagnosed with both schizophrenia and a cannabis use disorder will be randomized to a 12-week treatment course with either clozapine or risperidone (another commonly prescribed antipsychotic medication) to test the hypothesis that patient treated with clozapine will have decreased cannabis use as compared to patients treated with risperidone.
Should this study indicate that clozapine will lessen marijuana use in persons diagnosed with schizophrenia more than risperidone, it will provide evidence needed to begin to shift clinical practice toward its use in this population.
Read the detailed description
Cannabis use disorder (CUD), which is up to ten times more common in patients with schizophrenia (SCZ) than in the general population, worsens the course of this severe psychiatric disorder. Since SCZ occurs in 1% of the population, the co-occurrence of CUD in 13% to 42% of people with this disorder presents society with an important public health problem. Unfortunately, most antipsychotics available for treatment of patients with SCZ do not appear to limit their cannabis use. Moreover, the one antipsychotic that preliminary data suggest may well limit cannabis use in these patients, clozapine (CLOZ), is not used for this purpose; it is reserved for patients whose psychosis is treatment resistant.
The overarching idea behind this proposal, however, is that CLOZ's use is being unreasonably restricted and should be made more widely available for patients with SCZ who have a co-occurring CUD but whose psychosis is not necessarily treatment resistant. This notion is supported by our preliminary clinical and animal data on the effects of CLOZ, as well as our neurobiological model of the basis of cannabis use in patients with SCZ that provides a pharmacologic rationale for this effect of CLOZ.
Even given all the arguments favoring the potential benefits of CLOZ in patients with SCZ and CUD, however, its side effect profile will likely limit its use until a fully powered study demonstrates its ability to decrease cannabis use in patients with SCZ. This proposal aims to launch such a study. If, as we hypothesize, this study confirms and extends our previous preliminary data of the effects of CLOZ in patients with SCZ and CUD, it will provide a strong impetus to expand the use of CLOZ in this population.
In the proposed study, 132 patients who are comorbid for both SCZ and CUD will be randomized to a 12-week treatment course with either CLOZ or risperidone (RISP) to test the hypothesis that patients treated with CLOZ will have decreased cannabis use as compared to patients treated with RISP. In addition, the study will determine whether patients treated with CLOZ will have improvements in psychiatric symptoms, quality of life neuropsychological functions as compared to those taking RISP. We will also explore whether patients taking CLOZ show improved reward responsiveness as compared to those taking RISP. Finally, this study will explore whether those patients with the val/val genotype at the Catechol-O-methyltransferase (COMT) Val158Met locus are more likely to decrease cannabis use during CLOZ treatment than are those without the val/val COMT genotype.
Should this study indicate that CLOZ will lessen cannabis use in patients with SCZ more than RISP, it will provide evidence needed to begin to shift clinical practice toward its use in these patients.
- Conditions
- Schizophrenia, Cannabis Abuse, Cannabis Dependence, Dual Diagnosis
- Being tested
- Clozapine, Risperidone
- Keywords
- Schizophrenia, Cannabis Abuse, Cannabis Dependence, Dual Diagnosis, Clozapine, Risperidone
- Medical subject headings
- Schizophrenia, Marijuana Abuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClozapineDrug
Also called Clozaril
Clozapine: target dose of 400mg per day with a maximum dose of 550mg per day
RisperidoneDrug
Also called Risperdal
Clozapine: target dose of 4mg per day with a maximum dose of 6mg per day
| Study group | Role | What they receive |
|---|---|---|
| Clozapine | Experimental | The blinded CLOZ will be titrated on a recommended standard schedule, supervised by a study physician (or other prescriber) who can make the necessary adjustments to account for symptom control and tolerability. The titration is recommended to begin at 12.5 mg and then increase while the open-label base antipsychotic is tapered with a recommended goal of decreasing the base antipsychotic by 25% each week. If clinically tolerated, the target dose of CLOZ is 400 mg/day. Receives: Drug: Clozapine |
| Risperidone | Active comparator | The blinded RISP will also be titrated in the first weeks, using a titration schedule, with a target dose of 4 mg/day, while the open label base antipsychotic is tapered in a similar fashion. Receives: Drug: Risperidone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Average Over Time of Intensity of Cannabis Use (Used to Evaluate Treatment Efficacy)
Intensity of cannabis use is obtained each week retrospectively as the number of joints smoked during the prior week (assessed using the Timeline Followback). Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.
Measured: 12 weeks
Average Over Time of Frequency of Cannabis Use
Frequency of cannabis use is obtained each week retrospectively as the number of days of cannabis use during the prior week (assessed using the Timeline Followback). Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2012 (estimated)
- Study start1 May 2013
- Primary completion29 Mar 2017
- Study completion29 Mar 2017
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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dartmouth-Hitchcock Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of South Carolina, Michigan State University, University of Miami, University of Massachusetts, Worcester
- Responsible party
- Sponsor
- Investigators
- Alan I Green, MD, Study chair, Dartmouth College
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01639872
- Sponsor's protocol ID
- 1R01DA032533-01A1 D13012
- Other IDs
- 1R01DA032533-01A1
- Acronym
- CLOCS
- Status last verified
- Apr 2020
- First submitted
- 11 Jul 2012
- Last updated
- 5 May 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clozapine for Cannabis Use Disorder in Schizophrenia
- ClinicalTrials.gov ID
- NCT01639872
- Acronym / sponsor ID
- CLOCS / 1R01DA032533-01A1 D13012
- Conditions
- Schizophrenia, Cannabis Abuse, Cannabis Dependence, Dual Diagnosis
- Keywords
- Schizophrenia, Cannabis Abuse, Cannabis Dependence, Dual Diagnosis, Clozapine, Risperidone
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Dartmouth-Hitchcock Medical CenterUniversity, hospital or other
- Collaborators
- University of South Carolina, Michigan State University, University of Miami, University of Massachusetts, Worcester
- Study start
- 1 May 2013 (actual)
- Primary completion
- 29 Mar 2017 (actual)
- Study completion
- 29 Mar 2017 (actual)
- First posted
- 13 Jul 2012 (estimated)
- Results
- Posted 26 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Many individuals with schizophrenia also suffer from marijuana addiction that worsens their problems related to schizophrenia. Most of the medications prescribed for schizophrenia have no effect on reducing marijuana use. Preliminary data suggests that clozapine, an atypical antipsychotic, may limit marijuana use in people diagnosed with schizophrenia, but it is not commonly used due to its side effects and is reserved for people who do not respond to other antipsychotic medications.
In the proposed study, 132 individuals who are diagnosed with both schizophrenia and a cannabis use disorder will be randomized to a 12-week treatment course with either clozapine or risperidone (another commonly prescribed antipsychotic medication) to test the hypothesis that patient treated with clozapine will have decreased cannabis use as compared to patients treated with risperidone.
Should this study indicate that clozapine will lessen marijuana use in persons diagnosed with schizophrenia more than risperidone, it will provide evidence needed to begin to shift clinical practice toward its use in this population.
Detailed description
Cannabis use disorder (CUD), which is up to ten times more common in patients with schizophrenia (SCZ) than in the general population, worsens the course of this severe psychiatric disorder. Since SCZ occurs in 1% of the population, the co-occurrence of CUD in 13% to 42% of people with this disorder presents society with an important public health problem. Unfortunately, most antipsychotics available for treatment of patients with SCZ do not appear to limit their cannabis use. Moreover, the one antipsychotic that preliminary data suggest may well limit cannabis use in these patients, clozapine (CLOZ), is not used for this purpose; it is reserved for patients whose psychosis is treatment resistant.
The overarching idea behind this proposal, however, is that CLOZ's use is being unreasonably restricted and should be made more widely available for patients with SCZ who have a co-occurring CUD but whose psychosis is not necessarily treatment resistant. This notion is supported by our preliminary clinical and animal data on the effects of CLOZ, as well as our neurobiological model of the basis of cannabis use in patients with SCZ that provides a pharmacologic rationale for this effect of CLOZ.
Even given all the arguments favoring the potential benefits of CLOZ in patients with SCZ and CUD, however, its side effect profile will likely limit its use until a fully powered study demonstrates its ability to decrease cannabis use in patients with SCZ. This proposal aims to launch such a study. If, as we hypothesize, this study confirms and extends our previous preliminary data of the effects of CLOZ in patients with SCZ and CUD, it will provide a strong impetus to expand the use of CLOZ in this population.
In the proposed study, 132 patients who are comorbid for both SCZ and CUD will be randomized to a 12-week treatment course with either CLOZ or risperidone (RISP) to test the hypothesis that patients treated with CLOZ will have decreased cannabis use as compared to patients treated with RISP. In addition, the study will determine whether patients treated with CLOZ will have improvements in psychiatric symptoms, quality of life neuropsychological functions as compared to those taking RISP. We will also explore whether patients taking CLOZ show improved reward responsiveness as compared to those taking RISP. Finally, this study will explore whether those patients with the val/val genotype at the Catechol-O-methyltransferase (COMT) Val158Met locus are more likely to decrease cannabis use during CLOZ treatment than are those without the val/val COMT genotype.
Should this study indicate that CLOZ will lessen cannabis use in patients with SCZ more than RISP, it will provide evidence needed to begin to shift clinical practice toward its use in these patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Clozapine | Experimental | Drug: ClozapineThe blinded CLOZ will be titrated on a recommended standard schedule, supervised by a study physician (or other prescriber) who can make the necessary adjustments to account for symptom control and tolerability. The titration is recommended to begin at 12.5 mg and then increase while the open-label base antipsychotic is tapered with a recommended goal of decreasing the base antipsychotic by 25% each week. If clinically tolerated, the target dose of CLOZ is 400 mg/day. |
| Risperidone | Active comparator | Drug: RisperidoneThe blinded RISP will also be titrated in the first weeks, using a titration schedule, with a target dose of 4 mg/day, while the open label base antipsychotic is tapered in a similar fashion. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Clinical diagnosis of schizophrenia
- Clinical diagnosis of a cannabis use disorder (abuse or dependence)
Key exclusion criteria (4 listed)
- Pregnant,trying to become pregnant or nursing
- History of a seizure disorder
- Current treatment with clozapine or risperidone
- Contraindication to treatment with clozapine or risperidone
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 |
|---|---|---|
| ClozapineAlso: ClozarilClozapine: target dose of 400mg per day with a maximum dose of 550mg per day | Drug | Clozapine |
| RisperidoneAlso: RisperdalClozapine: target dose of 4mg per day with a maximum dose of 6mg per day | Drug | Risperidone |
Primary outcome
Average Over Time of Intensity of Cannabis Use (Used to Evaluate Treatment Efficacy)
Time frame: 12 weeks
Intensity of cannabis use is obtained each week retrospectively as the number of joints smoked during the prior week (assessed using the Timeline Followback). Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.
Average Over Time of Frequency of Cannabis Use
Time frame: 12 weeks
Frequency of cannabis use is obtained each week retrospectively as the number of days of cannabis use during the prior week (assessed using the Timeline Followback). Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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 study chair
Dartmouth College
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Clozapine and Risperidone in people with Schizophrenia and Cannabis Abuse, run by Dartmouth-Hitchcock Medical Center at 9 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 2 inclusion and 4 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 5 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 26 Dec 2019). 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?
Average Over Time of Intensity of Cannabis Use (Used to Evaluate Treatment Efficacy) (time frame: 12 weeks). The study lists 2 primary outcomes in all. 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 5 May 2020.