Combination of Dronabinol and Clonidine for Cannabis Dependence in Patients With Schizophrenia

NCT ID: NCT01598896

Last Updated: 2018-08-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-31
• Study Completion Date: 2017-08-31

Brief Summary

Cannabis use disorders are an important public health problem in the United States, but no effective pharmacotherapies are available to treat these disorders. People with schizophrenia are more likely than healthy people to abuse cannabis. Cannabis use may worsen clinical outcomes in this group, making the identification of pharmacotherapy to treat cannabis dependence in those with schizophrenia important. The investigators intend to test the combination of dronabinol, a cannabinoid agonist, and the α2-adrenergic agonist clonidine, for cannabis dependence in subjects with schizophrenia. The combination of dronabinol and clonidine may alleviate cannabis withdrawal symptoms while allowing treatment-seeking outpatients to benefit from medical management (MM) sessions when they are trying to stop using cannabis. The investigators propose to assess the relationship of dronabinol and clonidine, when added to MM, on cannabis use patterns in cannabis-dependent patients with schizophrenia.

Hypothesis: The investigators predict that combination pharmacotherapy of dronabinol and clonidine will significantly reduce cannabis use compared to those receiving placebo.

Detailed Description

Subjects will receive either the combination of dronabinol and clonidine or placebo in addition to medical management (MM) over a 10-week treatment period. Following treatment completion, subjects will have follow-up visits until 14 weeks after treatment initiation. This pilot study will evaluate the feasibility of the combination of dronabinol and clonidine for cannabis dependence and will establish effect sizes for a larger trial.

Cannabis use disorders are highly prevalent in the United States and rising among high school seniors, making the identification of efficacious treatments for cannabis dependence of critical clinical and public health significance. Schizophrenia is overrepresented among those with cannabis dependence. At the completion of this study, the investigators hope to have improved our understanding of the relationship of the pharmacotherapy combination of dronabinol and clondine on cannabis use.

Conditions

Cannabis Dependence; Marijuana Dependence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Dronabinol + Clonidine

Dronabinol titrated to 5 mg three times daily, Clonidine 0.1 mg twice daily

Group Type: EXPERIMENTAL

Dronabinol

Intervention Type: DRUG

Dronabinol titrated to 5 mg three times daily

Clonidine

Intervention Type: DRUG

Clonidine 0.1 mg twice daily

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

One placebo capsule by mouth twice daily

Interventions

Dronabinol

Dronabinol titrated to 5 mg three times daily

Intervention Type: DRUG

Clonidine

Clonidine 0.1 mg twice daily

Intervention Type: DRUG

Placebo

One placebo capsule by mouth twice daily

Intervention Type: DRUG

Other Intervention Names

Marinol, CSA Drug Code 7369, Schedule III, NDC 54868-3189-0; Catapres, NDC 16590-266-30

Eligibility Criteria

Inclusion Criteria

1. Age range 18-45 years

2. DSM-IV diagnosis of cannabis dependence, based on the Structured Clinical Interview for DSM-IV (SCID)

3. DSM-IV diagnosis of schizophrenia or schizoaffective disorder, based on the Structured Clinical Interview for DSM-IV (SCID)

4. express a desire to quit cannabis use within the next 30 days

5. have used cannabis on ≥20 days within the past 30 days (i.e., an average of ≥5 day per week)

6. identify cannabis as their primary drug of abuse; 6) stable on antipsychotic medication for ≥1 month

7. for women of childbearing age, a negative pregnancy test at screening with agreement to use adequate contraception to prevent pregnancy and monthly pregnancy tests

8. consent for us to communicate with their prescribing clinician if one exists

9. furnish the names of 2 locators, who would assist study staff in locating them during the study period

10. live close enough to McLean Hospital to attend study visits

11. plan to stay in the Boston area for the next 3 months

12. are willing and able to sign informed consent.

Exclusion Criteria

1. Current diagnosis of other drug or alcohol dependence (excluding nicotine)

2. significant cardiac disease as indicated by history or suspected by abnormal ECG or history of cardiac symptoms

3. Positive and Negative Syndrome Scale (PANSS) subscale for positive symptoms of psychosis item > 3 (moderate) at baseline evaluation

4. current medical condition that could prevent regular study attendance

5. liver function tests >3 times the upper limit of normal range

6. history of seizure disorder or history of head trauma or CNS insult that could predispose the subject to seizures

7. taking clozapine

8. current suicidal risk

9. bradycardia less than or equal to 50 bpm, supine blood pressure of less than or equal to 100/65, a seated blood pressure of less than or equal to 90/60, or orthostatic change of >20 systolic or >10 diastolic on standing, at screening or any pre-dose assessment, or symptoms attributable to low BP (i.e. lightheadedness or dizziness on standing)

10. mental retardation or organic mental disorder

11. currently in a residential treatment setting in which substance use is monitored and restricted, since the restricted access to drugs could represent an important confounding variable

12. pregnant, nursing, or, if a woman of childbearing potential, not using a form of birth control judged by the investigator to be effective

13. concomitant treatment with opioid analgesics, sedative hypnotics, or other known CNS depressants

14. known hypersensitivity to cannabinoids or sesame oil or clonidine

15. disease of the gastrointestinal system, liver, or kidneys that may impede metabolism or excretion of dronabinol

16. inability to read or write in English that would hinder their ability to follow study procedures

17. history of seizures or a family history of seizures.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brain & Behavior Research Foundation

OTHER

Sponsor Role: collaborator

Mclean Hospital

OTHER

Sponsor Role: lead

Responsible Party

Kevin P. Hill, MD, MHS

Instructor in Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kevin P Hill, MD, MHS

Role: PRINCIPAL_INVESTIGATOR

Mclean Hospital

Locations

McLean Hospital

Belmont, Massachusetts, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Brain and Behavior Research

Identifier Type: OTHER

Identifier Source: secondary_id

2010P-002262

Identifier Type: -

Identifier Source: org_study_id