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Quetiapine Pharmacotherapy for Cannabis Dependence (QUEST)

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ClinicalTrials.gov Identifier: NCT01697709
Recruitment Status : Completed
First Posted : October 2, 2012
Last Update Posted : May 21, 2018
Sponsor:
Collaborator:
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
John Mariani MD, New York State Psychiatric Institute

September 28, 2012
October 2, 2012
May 21, 2018
October 1, 2012
April 30, 2017   (Final data collection date for primary outcome measure)
Marijuana Use [ Time Frame: 12 weeks ]
The daily dollar value of marijuana used averaged over a one-week period as recorded by the Timeline Followback method and confirmed by creatinine-normalized quantitative urine THC levels.
Same as current
Complete list of historical versions of study NCT01697709 on ClinicalTrials.gov Archive Site
  • Marijuana Abstinence [ Time Frame: 12 weeks ]
    The number of abstinent days per week as recorded by the Timeline Followback method and confirmed by creatinine-normalized quantitative urine THC levels
  • Urine toxicology [ Time Frame: 12 weeks ]
    Twice weekly urine toxicology samples negative for cannabinoids - dichotomous longitudinal
  • Marijuana withdrawal symptoms [ Time Frame: 12 weeks ]
    Measured by weekly Marijuana Withdrawal Checklist (MWC) - continuous longitudinal
  • Marijuana craving [ Time Frame: 12 weeks ]
    Measured by weekly Marijuana Craving Questionnaire (MCQ) - continuous longitudinal
  • Sleep disturbance [ Time Frame: 12 weeks ]
    Measured by the Medical Outcomes Study—Sleep Scale (MOS-SS) - continuous longitudinal
Same as current
Retention [ Time Frame: 12 weeks ]
Study drop out will be recorded.
Same as current
 
Quetiapine Pharmacotherapy for Cannabis Dependence
Quetiapine Pharmacotherapy for Cannabis Dependence

Despite a benign public perception, marijuana use disorders represent a significant public health problem. The development of safe and effective pharmacotherapies for marijuana dependence is an important unmet public health need. Quetiapine, an effective atypical antipsychotic that acts by blocking serotonin type 2A, dopamine type 2, histamine type 1, and adrenergic receptors, is a promising treatment for substance use disorders. In animal models, quetiapine blocks the enhancement of reward by cocaine, which is likely due to its actions on both dopamine and non-dopamine neurotransmission. Clinical studies of quetiapine have shown benefit for the treatment of alcohol and cocaine use disorders.

Conceptually, the clinically prominent effects of quetiapine, namely sedation, anxiolysis, mood stabilization and appetite stimulation, are a good match for the symptoms of marijuana withdrawal. Most importantly, an open-label dose-finding study of quetiapine for the treatment of marijuana dependence conducted by our research group determined that quetiapine was well-tolerated and associated with reductions in marijuana use indicating that it is a promising agent deserving of further study in marijuana-dependent outpatients.

The proposed research project is a randomized double-blind placebo-controlled clinical trial to evaluate the efficacy of quetiapine for the treatment of marijuana dependence over a 12-week period. All participants will receive Medical Management, a medication adherence focused psychosocial intervention that facilitates compliance with study medication and other study procedures, promotes abstinence from marijuana and other substances, and encourages mutual-support group attendance. All participants will receive voucher incentives for compliance with study visit attendance, returning study medication bottles, and completing other study procedures, with the objective of achieving a highly compliant sample. The goal of this phase II clinical trial is to build on our promising open-label pilot study results and examine the efficacy of quetiapine on participants' marijuana consumption under placebo-controlled double-blind conditions using an abstinence-initiation model, where participants will be using marijuana regularly at study entry, reduce their use, and then achieve abstinence. The specific aims of the projects are to determine whether quetiapine is superior to placebo in 1) reducing marijuana use and 2) achieving abstinence.

In a 12-week randomized double-blind placebo-controlled clinical trial, we will evaluate the efficacy of quetiapine for the treatment of marijuana dependence in 150 outpatients. Participants will be randomly assigned to treatment under double-blind conditions with either a fixed dosing schedule of quetiapine or placebo. All participants will receive Medical Management, a medication adherence focused psychosocial intervention that facilitates compliance with study medication and other study procedures, and promotes abstinence from marijuana and other substances. All participants will receive progressive voucher incentives for compliance with study visit attendance and completing other study procedures, with the objective of achieving a highly compliant sample.

The results of a dose-finding pilot study of quetiapine for the treatment of marijuana dependence (see Preliminary Studies) suggests that the ideal dosing for the proposed project is a single 300 mg dose every evening, achieved after a gradual three-week titration. Clinical experience with this medication for treatment of marijuana dependence indicates that a gradual upward titration of dose is advisable to maximize tolerability and that morning dosing was poorly tolerated. Quetiapine (immediate release formulation) will be administered in 25 and 100 mg capsules; placebo capsules will appear identical to the quetiapine capsules. Participants in both treatment arms will take the same number of pills on the same schedule. Study medication will be dispensed on a weekly basis starting with the baseline visit. Quetiapine will be titrated over a three-week period to the target dose of 300 mg or the maximum tolerated dose. The research psychiatrist will make dose reductions for tolerability if necessary.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Cannabis Dependence
  • Drug: Quetiapine
    Quetiapine pharmacotherapy for cannabis dependence
    Other Name: Seroquel
  • Drug: Placebo
    placebo capsules
    Other Name: Matched Placebo
  • Placebo Comparator: Placebo
    Placebo medication
    Intervention: Drug: Placebo
  • Experimental: quetiapine
    Quetiapine treatment
    Intervention: Drug: Quetiapine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
130
150
April 30, 2017
April 30, 2017   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Meets DSM-IV-TR criteria for current marijuana dependence
  2. Reports using marijuana an average of 5 days per week over the past 28 days
  3. Between the ages of 18 and 60
  4. Able to provide informed consent and comply with study procedures
  5. Seeking treatment for cannabis dependence

Exclusion Criteria:

  1. Lifetime DSM-IV diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder.
  2. Current DSM-IV criteria for any other psychiatric disorder that may, according to investigator's judgment, require either pharmacological or non-pharmacological intervention over the course of the study.
  3. Patients prescribed psychotropic medications.
  4. History of allergic reaction, intolerance, or hypersensitivity to Quetiapine.
  5. Pregnancy, lactation, or failure to use adequate contraceptive methods in female patients who are currently engaging in sexual activity with men.
  6. Unstable medical conditions, such as poorly controlled hypertension which might make participation hazardous.
  7. Diabetes (whether controlled or not), meeting criteria for metabolic syndrome as defined by the NCEP (any 3 of the following: a. obesity [waist circumference > 40 inches], b. hyperglycemia [fasting glucose > 100 mg/dl or Rx], c. dyslipidemia [TG > 150 mg/dl or Rx], d. dyslipidemia [HDL cholesterol; 40 mg/dl (male), 50 mg/dl (female) or Rx], e. hypertension [130 mmHg systolic or > 85 mmHg diastolic or Rx]. Participants with a BMI > 35 will be excluded.
  8. Current DSM-IV diagnosis of an alcohol or substance use disorder (abuse or dependence) other than marijuana or nicotine dependence.
  9. Positive confirmed result on urine toxicology screen.
  10. Are legally mandated to participate in a substance use disorder treatment program.
  11. Increased risk for suicide.
  12. QTc prolongation (screening electrocardiogram with Qtc > 450 msec for men, QTc > 470 msec for women) or history of QTc prolongation or using concomitant medications which prolong QTc interval.
Sexes Eligible for Study: All
18 Years to 60 Years   (Adult)
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01697709
6623
1R01DA031826 ( U.S. NIH Grant/Contract )
Yes
Not Provided
Plan to Share IPD: No
John Mariani MD, New York State Psychiatric Institute
New York State Psychiatric Institute
National Institute on Drug Abuse (NIDA)
Principal Investigator: John J Mariani, MD Columbia University/NYSPI
New York State Psychiatric Institute
May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP