SchizophreniaPhase 4NCT00498550
Treatment of Schizophrenia and Comorbid Cannabis Use Disorder: Comparing Clozapine to Treatment-as-Usual
A Phase 4 study testing Clozapine and Treatment as usual in people with Schizophrenia and Dual Diagnosis, run by Dartmouth-Hitchcock Medical Center at 4 sites in United States.
Trial summary
Many individuals with schizophrenia also suffer from marijuana addiction. Clozapine, an atypical antipsychotic medication, may prove useful at preventing drug relapse in schizophrenic individuals who are seeking treatment for marijuana addiction. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia, Dual Diagnosis, Schizoaffective Disorder
- What is being tested?
- Clozapine and Treatment as usual
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 4 sitesUnited States
- Study dates
- Oct 2000to Mar 2009
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Meets Diagnostic and Statical Manual of Mental Disorders IV (DSM-IV) diagnostic criteria for schizophrenia or schizoaffective disorder
- Meets diagnostic criteria for marijuana use disorder, as determined by a rating of 3 or higher on the Drug Use Scale (Abuse or Dependence)
- Used marijuana on 5 or more days during the 3 weeks prior to study entry
- Taking any oral antipsychotic other than clozapine in the month prior to study entry. (Patients may take a second oral antipsychotic medication, if approved by the Medication Adjustment Group)
- If female, willing to use effective contraception throughout the study
Who cannot join
- Unable to take clozapine for medical reasons, including previous clozapine-induced granulocytopenia, myeloproliferative disorder, white blood cell count less than 3500/mm3, or history of seizures
- Currently taking clozapine
- Currently taking other psychotropic medications for the treatment of substance use (e.g., disulfiram, naltrexone, acamprosate, inderol, tegretol, topiramate, and pramipexole)
- Participated in a clinical trial of an investigational drug within 30 days of study entry
- Currently participating in a psychosocial intervention clinical trial
- Has medical or legal problems that may entail a jail or hospital stay during the study
Show all 9Show fewer
- Has a developmental disability that would make study participation difficult
- Currently enrolled in a live-in treatment program for substance use disorders
- Pregnant or plans to become pregnant during the study
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University South Carolina
Columbia, South Carolina, 29203
University Missouri
Kansas City, Missouri, 64108
West LA VAHCS
Los Angeles, California, 90073
Mental Health Center of Greater Manchester
Manchester, New Hampshire, 03101
About this study
Official title: Cannabis and Schizophrenia: Effects of Clozapine
Many individuals with schizophrenia also suffer from marijuana addiction. Clozapine, an atypical antipsychotic medication, may prove useful at preventing drug relapse in schizophrenic individuals who are seeking treatment for marijuana addiction. The purpose of this study is to compare the effectiveness of clozapine, vs. treatment-as-usual with other oral antipsychotics at reducing marijuana use in schizophrenic individuals.
Read the detailed description
Individuals with schizophrenia have a high risk of becoming addicted to drugs; between 13 to 42% of schizophrenics are addicted to marijuana. These individuals often have difficulties adhering to a substance abuse treatment program, and have an increased chance of marijuana relapse. Marijuana use by schizophrenics has also been associated with clinical exacerbations, noncompliance with antipsychotic medications, poor global functioning, and increased rehospitalization rates. While antipsychotic medications are often effective in controlling symptoms of schizophrenia, they are not always effective in preventing substance abuse. Clozapine, an atypical antipsychotic drug, is currently used to treat schizophrenia. Preliminary research has shown that clozapine is more successful at reducing drug relapse rates in individuals with schizophrenia, as compared to other antipsychotic medications, including olanzapine and risperidone. The purpose of this study is to compare the effectiveness of clozapine as compared to other oral antipsychotic treatment, including combinations of up to two antipsychotics, in reducing marijuana use in schizophrenic individuals.
This study will enroll individuals with schizophrenia who are currently taking any oral antipsychotic other than clozapine, including those taking up to two oral antipsychotic, and who are also addicted to marijuana. The study will begin with a 1-week assessment phase, during which all participants will continue taking olanzapine or risperidone. Participants will undergo a physical examination and have blood drawn for laboratory tests. Information pertaining to their medical, psychiatric, and substance use history will also be collected. Urine tests and breathalyzers will be used to screen for the presence of alcohol and drugs. Following the assessment phase, participants will be randomly assigned to switch to clozapine or remain on their prestudy antipsychotic for 12 weeks. Participants remaining on their prestudy antipsychotic treatment will continue to receive the same dose for the entire study. Participants taking clozapine will initially receive a daily dose of 12.5 mg, which will be increased to a maximum of 400 mg per day, as tolerated. Study visits will take place once a week. At each visit, medication side effects, physical and psychological symptoms, substance use, treatment services received, and living situation will be assessed. Blood will be drawn for laboratory tests. Drug and alcohol levels will be monitored three times a week through urine and breathalyzer tests. Quality of life questionnaires will be administered once a month.
- Conditions
- Schizophrenia, Dual Diagnosis, Schizoaffective Disorder, Psychotic Disorder, Cannabis Abuse
- Being tested
- Clozapine, Treatment as usual
- Keywords
- Clozapine, Schizophrenia, Dual Diagnosis, Substance Abuse, Cannabis Abuse
- Medical subject headings
- Schizophrenia, Psychotic Disorders, Marijuana Abuse, Substance-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClozapineDrug
Also called Clozaril
Clozapine up to 550mg per day
Remain on pre-study antipsychotic treatment
| Study group | Role | What they receive |
|---|---|---|
| Clozapine | Experimental | Clozapine, Clozaril Receives: Drug: Clozapine |
| Treatment as usual | Active comparator | Treatment as usual with any antipsychotic other than Clozapine. Receives: Drug: Treatment as usual |
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 for each week retrospectively as the number of joints smoked during the prior week (assessed by the Timeline Followback Scale). 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: Week 1 to week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2007 (estimated)
- Study startOct 2000
- Primary completionMar 2009
- Study completionMar 2009
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
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dartmouth-Hitchcock Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA), University of Missouri, Kansas City, VA Medical Center-West Los Angeles, University of South Carolina
- Responsible party
- Principal investigator, Alan Green, Dartmouth-Hitchcock Medical Center
- Investigators
- Alan Green, MD, Principal investigator, Dartmouth-Hitchcock Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00498550
- Sponsor's protocol ID
- NCT00149955
- Other IDs
- R01DA013196, DPMCDA
- Status last verified
- Feb 2019
- First submitted
- 6 Jul 2007
- Last updated
- 13 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cannabis and Schizophrenia: Effects of Clozapine
- ClinicalTrials.gov ID
- NCT00498550
- Acronym / sponsor ID
- NCT00149955
- Conditions
- Schizophrenia, Dual Diagnosis, Schizoaffective Disorder, Psychotic Disorder, Cannabis Abuse
- Keywords
- Clozapine, Schizophrenia, Dual Diagnosis, Substance Abuse, Cannabis Abuse
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Dartmouth-Hitchcock Medical CenterUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA), University of Missouri, Kansas City, VA Medical Center-West Los Angeles, University of South Carolina
- Study start
- Oct 2000
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 10 Jul 2007 (estimated)
- Results
- Posted 19 Jan 2012
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. Clozapine, an atypical antipsychotic medication, may prove useful at preventing drug relapse in schizophrenic individuals who are seeking treatment for marijuana addiction. The purpose of this study is to compare the effectiveness of clozapine, vs. treatment-as-usual with other oral antipsychotics at reducing marijuana use in schizophrenic individuals.
Detailed description
Individuals with schizophrenia have a high risk of becoming addicted to drugs; between 13 to 42% of schizophrenics are addicted to marijuana. These individuals often have difficulties adhering to a substance abuse treatment program, and have an increased chance of marijuana relapse. Marijuana use by schizophrenics has also been associated with clinical exacerbations, noncompliance with antipsychotic medications, poor global functioning, and increased rehospitalization rates. While antipsychotic medications are often effective in controlling symptoms of schizophrenia, they are not always effective in preventing substance abuse. Clozapine, an atypical antipsychotic drug, is currently used to treat schizophrenia. Preliminary research has shown that clozapine is more successful at reducing drug relapse rates in individuals with schizophrenia, as compared to other antipsychotic medications, including olanzapine and risperidone. The purpose of this study is to compare the effectiveness of clozapine as compared to other oral antipsychotic treatment, including combinations of up to two antipsychotics, in reducing marijuana use in schizophrenic individuals.
This study will enroll individuals with schizophrenia who are currently taking any oral antipsychotic other than clozapine, including those taking up to two oral antipsychotic, and who are also addicted to marijuana. The study will begin with a 1-week assessment phase, during which all participants will continue taking olanzapine or risperidone. Participants will undergo a physical examination and have blood drawn for laboratory tests. Information pertaining to their medical, psychiatric, and substance use history will also be collected. Urine tests and breathalyzers will be used to screen for the presence of alcohol and drugs. Following the assessment phase, participants will be randomly assigned to switch to clozapine or remain on their prestudy antipsychotic for 12 weeks. Participants remaining on their prestudy antipsychotic treatment will continue to receive the same dose for the entire study. Participants taking clozapine will initially receive a daily dose of 12.5 mg, which will be increased to a maximum of 400 mg per day, as tolerated. Study visits will take place once a week. At each visit, medication side effects, physical and psychological symptoms, substance use, treatment services received, and living situation will be assessed. Blood will be drawn for laboratory tests. Drug and alcohol levels will be monitored three times a week through urine and breathalyzer tests. Quality of life questionnaires will be administered once a month.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Clozapine | Experimental | Drug: ClozapineClozapine, Clozaril |
| Treatment as usual | Active comparator | Drug: Treatment as usualTreatment as usual with any antipsychotic other than Clozapine. |
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 Diagnostic and Statical Manual of Mental Disorders IV (DSM-IV) diagnostic criteria for schizophrenia or schizoaffective disorder
- Meets diagnostic criteria for marijuana use disorder, as determined by a rating of 3 or higher on the Drug Use Scale (Abuse or Dependence)
- Used marijuana on 5 or more days during the 3 weeks prior to study entry
- Taking any oral antipsychotic other than clozapine in the month prior to study entry. (Patients may take a second oral antipsychotic medication, if approved by the Medication Adjustment Group)
- If female, willing to use effective contraception throughout the study
Key exclusion criteria (9 listed)
- Unable to take clozapine for medical reasons, including previous clozapine-induced granulocytopenia, myeloproliferative disorder, white blood cell count less than 3500/mm3, or history of seizures
- Currently taking clozapine
- Currently taking other psychotropic medications for the treatment of substance use (e.g., disulfiram, naltrexone, acamprosate, inderol, tegretol, topiramate, and pramipexole)
- Participated in a clinical trial of an investigational drug within 30 days of study entry
- Currently participating in a psychosocial intervention clinical trial
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 up to 550mg per day | Drug | Clozapine |
| Treatment as usualRemain on pre-study antipsychotic treatment | Drug | Treatment as usual |
Primary outcome
Average Over Time of Intensity of Cannabis Use (Used to Evaluate Treatment Efficacy)
Time frame: Week 1 to week 12
Intensity of cannabis use is obtained for each week retrospectively as the number of joints smoked during the prior week (assessed by the Timeline Followback Scale). 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 13 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Schizophrenia
RecruitingPhase 3
A Study to Evaluate the Long-term Safety and Tolerability of Xanomeline and Trospium Chloride for the Treatment of Psychiatric Disorders in Children and Adolescents
Schizophrenia, Autism-Related Irritability
Not yet recruiting
Deep Brain Stimulation for Treatment-Resistant Schizophrenia
Treatment Resistant Disorders
Not yet recruitingObservational study
Sleep Monitoring for Early Detection of Relapse in People With Schizophrenia or Bipolar Disorder Receiving Usual Treatment
Bipolar Disorder (BD), SCHIZOPHRENIA 1 (Disorder)
Not yet recruitingPhase 1
Pharmacokinetics and Relative Bioavailability of Intranasal vs Intramuscular Olanzapine in Healthy Adult Participants
Healthy Adult Participants
Active, not recruiting
Designing and Evaluating a Classroom-Based Mental Health Programme for Adolescents.
Mental Health Promotion
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 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 4 study testing Clozapine and Treatment as usual in people with Schizophrenia and Dual Diagnosis, 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 9 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 13 Mar 2019. 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 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 19 Jan 2012). 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: Week 1 to week 12). 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 13 Mar 2019.