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

NCT01598896 | Terminated Phase 2 Results

• 2 other identifiers: 2010P-002262Brain and Behavior Research
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Cannabis Dependence; Marijuana Dependence

Keywords

Cannabis Dependence; Marijuana Dependence; Cannabis Use Disorders; Cannabis Withdrawal; Dronabinol; Clonidine; Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Cannabis Use at 10 Weeks

  Subject self-report hits of marijuana per day at week 10

  At 10 weeks

Secondary Outcomes (3)

• Change in Craving Symptoms From Baseline at 10 Weeks

  At 10 weeks

• Change From Baseline in Cannabis Use at 14 Weeks

  At 14 weeks

• Change in Craving Symptoms From Baseline at 14 Weeks

  At 14 weeks

Study Arms (2)

Dronabinol + Clonidine

EXPERIMENTAL

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

Drug: Dronabinol; Drug: Clonidine

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Dronabinol DRUG

Dronabinol titrated to 5 mg three times daily

Also known as: Marinol, CSA Drug Code 7369, Schedule III, NDC 54868-3189-0

Dronabinol + Clonidine

Clonidine DRUG

Clonidine 0.1 mg twice daily

Also known as: Catapres, NDC 16590-266-30

Dronabinol + Clonidine

Placebo DRUG

One placebo capsule by mouth twice daily

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age range 18-45 years
• DSM-IV diagnosis of cannabis dependence, based on the Structured Clinical Interview for DSM-IV (SCID)
• DSM-IV diagnosis of schizophrenia or schizoaffective disorder, based on the Structured Clinical Interview for DSM-IV (SCID)
• express a desire to quit cannabis use within the next 30 days
• have used cannabis on ≥20 days within the past 30 days (i.e., an average of ≥5 day per week)
• identify cannabis as their primary drug of abuse; 6) stable on antipsychotic medication for ≥1 month
• for women of childbearing age, a negative pregnancy test at screening with agreement to use adequate contraception to prevent pregnancy and monthly pregnancy tests
• consent for us to communicate with their prescribing clinician if one exists
• furnish the names of 2 locators, who would assist study staff in locating them during the study period
• live close enough to McLean Hospital to attend study visits
• plan to stay in the Boston area for the next 3 months
• are willing and able to sign informed consent.

You may not qualify if:

• Current diagnosis of other drug or alcohol dependence (excluding nicotine)
• significant cardiac disease as indicated by history or suspected by abnormal ECG or history of cardiac symptoms
• Positive and Negative Syndrome Scale (PANSS) subscale for positive symptoms of psychosis item \> 3 (moderate) at baseline evaluation
• current medical condition that could prevent regular study attendance
• liver function tests \>3 times the upper limit of normal range
• history of seizure disorder or history of head trauma or CNS insult that could predispose the subject to seizures
• taking clozapine
• current suicidal risk
• 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)
• mental retardation or organic mental disorder
• 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
• pregnant, nursing, or, if a woman of childbearing potential, not using a form of birth control judged by the investigator to be effective
• concomitant treatment with opioid analgesics, sedative hypnotics, or other known CNS depressants
• known hypersensitivity to cannabinoids or sesame oil or clonidine
• disease of the gastrointestinal system, liver, or kidneys that may impede metabolism or excretion of dronabinol

Sponsors & Collaborators

• Mclean Hospital: lead
• Brain & Behavior Research Foundation: collaborator

Study Sites (1)

McLean Hospital

Belmont, Massachusetts, 02478, United States

Location

MeSH Terms

Conditions

Marijuana Abuse; Schizophrenia

Interventions

Dronabinol; Clonidine

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals; Imidazolines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Due to lack of sufficient funds/resources, the sample size for this study is not large enough to extract any conclusive results. The high number of subjects withdrawing from the study early also hinders any possible conclusions.

Results Point of Contact

• Title: Dr. Kevin Hill
• Organization: Beth Israel Deaconess Medical Center

khill1@bidmc.harvard.edu

617-667-1504

Study Officials

• Kevin P Hill, MD, MHS

  Mclean Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Instructor in Psychiatry

Study Record Dates

• First Submitted: May 11, 2012
• First Posted: May 15, 2012
• Study Start: May 1, 2012
• Primary Completion: August 1, 2017
• Study Completion: August 1, 2017
• Last Updated: August 29, 2018
• Results First Posted: August 1, 2018

Record last verified: 2018-07

Locations

US (1)