QUEST: Quetiapine Pharmacotherapy for Cannabis Dependence

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01697709
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 130
• Location: 1
• Arms: 2
• Actual Duration (Months): 54.9
• Patients Per Site Per Month: 2.4

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Cannabis Dependence	Drug: Quetiapine; Drug: Placebo	Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 130 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Quetiapine Pharmacotherapy for Cannabis Dependence
• Actual Study Start Date: Oct 1, 2012
• Actual Primary Completion Date: Apr 30, 2017
• Actual Study Completion Date: Apr 30, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo medication	Drug: Placebo; placebo capsules; Other Names: Matched Placebo
Experimental: quetiapine Quetiapine treatment	Drug: Quetiapine; Quetiapine pharmacotherapy for cannabis dependence; Other Names: Seroquel

Outcome Measures

Primary Outcome Measures

1. Marijuana Use, Daily Dollar Averaged Over 7 Days During Each of 12 Weeks of Study [12 weeks or length of participants involvement]

   The median daily dollar value of marijuana used averaged over a one-week period for each of the 12 weeks as recorded by the Timeline Followback method

2. Number of Participants Stratified by Marijuana Abstinence Days Per Week [12 weeks or length of participation]

   The number of abstinent days per week over the 12 weeks of study as recorded by the Timeline Followback method. High Use group defined as 0-2 abstinent days per week, Medium Use Group as 3-5 abstinent days per week and Low Use Group as 6-7 abstinent days per week.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New York State Psychiatric Institute	New York	New York	United States	10032

Sponsors and Collaborators

• New York State Psychiatric Institute
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: John J Mariani, MD, Columbia University/NYSPI

Study Documents (Full-Text)

• Study Protocol - Jun 11, 2018
• Statistical Analysis Plan - Nov 7, 2011

More Information

Additional Information:

• Study web site

Publications

None provided.

• Responsible Party: John Mariani MD, research psychiatrist, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT01697709
• Other Study ID Numbers: 6623; 1R01DA031826
• First Posted: Oct 2, 2012
• Last Update Posted: Mar 5, 2019
• Last Verified: Feb 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by John Mariani MD, research psychiatrist, New York State Psychiatric Institute: cannabis; marijuana; pharmacotherapy
• Additional relevant MeSH terms: Marijuana Abuse; Quetiapine Fumarate

Study Results

Participant Flow

Pre-assignment Detail	Patients were randomized to one of the treatment arms at time of enrollment

Arm/Group Title	Placebo	Quetiapine
Arm/Group Description	Placebo medication Placebo: placebo capsules	Quetiapine treatment Quetiapine: Quetiapine pharmacotherapy for cannabis dependence
Period Title: Overall Study
STARTED	64	66
COMPLETED	34	38
NOT COMPLETED	30	28

Baseline Characteristics

Arm/Group Title	Placebo	Quetiapine	Total
Arm/Group Description	Placebo medication Placebo: placebo capsules	Quetiapine treatment Quetiapine: Quetiapine pharmacotherapy for cannabis dependence	Total of all reporting groups
Overall Participants	64	66	130
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.1 (8.7)	32.7 (9.5)	32.9 (9.1)
Sex: Female, Male (Count of Participants)
Female	14 21.9%	14 21.2%	28 21.5%
Male	50 78.1%	52 78.8%	102 78.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	15 23.4%	17 25.8%	32 24.6%
Not Hispanic or Latino	49 76.6%	49 74.2%	98 75.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	3 4.7%	1 1.5%	4 3.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	32 50%	24 36.4%	56 43.1%
White	18 28.1%	25 37.9%	43 33.1%
More than one race	3 4.7%	8 12.1%	11 8.5%
Unknown or Not Reported	8 12.5%	8 12.1%	16 12.3%
mood/anxiety disorder (Count of Participants)
Count of Participants [Participants]	14 21.9%	14 21.2%	28 21.5%
Marijuana using days past 28 days (days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [days]	26.8 (2.1)	26.4 (2.5)	26.6 (2.3)

Outcome Measures

1. Primary Outcome

Title	Marijuana Use, Daily Dollar Averaged Over 7 Days During Each of 12 Weeks of Study
Description	The median daily dollar value of marijuana used averaged over a one-week period for each of the 12 weeks as recorded by the Timeline Followback method
Time Frame	12 weeks or length of participants involvement

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Quetiapine
Arm/Group Description	Placebo medication Placebo: placebo capsules	Quetiapine treatment Quetiapine: Quetiapine pharmacotherapy for cannabis dependence
Measure Participants	64	66
week 1	14.00	7.00
week 2	10.00	8.00
week 3	7.14	5.86
week 4	6.43	5.71
week 5	6.43	4.29
week 6	5.71	4.11
week 7	3.70	3.57
week 8	2.86	3.43
week 9	6.43	3.00
week 10	5.35	2.86
week 11	3.21	2.86
week 12	1.00	2.14

2. Primary Outcome

Title	Number of Participants Stratified by Marijuana Abstinence Days Per Week
Description	The number of abstinent days per week over the 12 weeks of study as recorded by the Timeline Followback method. High Use group defined as 0-2 abstinent days per week, Medium Use Group as 3-5 abstinent days per week and Low Use Group as 6-7 abstinent days per week.
Time Frame	12 weeks or length of participation

Outcome Measure Data

Analysis Population Description

participants were included in the weekly analysis who were still active in the trial at each given week.

Arm/Group Title	Placebo	Quetiapine
Arm/Group Description	Placebo medication Placebo: placebo capsules	Quetiapine treatment Quetiapine: Quetiapine pharmacotherapy for cannabis dependence
Measure Participants	64	66
high use	5 7.8%	4 6.1%
medium use	9 14.1%	9 13.6%
low use	40 62.5%	46 69.7%
high use	8 12.5%	4 6.1%
medium use	7 10.9%	7 10.6%
low use	34 53.1%	44 66.7%
high use	9 14.1%	5 7.6%
medium use	5 7.8%	14 21.2%
low use	28 43.8%	33 50%
high use	8 12.5%	8 12.1%
medium use	9 14.1%	15 22.7%
low use	23 35.9%	26 39.4%
high use	10 15.6%	10 15.2%
medium use	7 10.9%	16 24.2%
low use	22 34.4%	21 31.8%
high use	13 20.3%	10 15.2%
medium use	4 6.3%	13 19.7%
low use	22 34.4%	23 34.8%
high use	12 18.8%	11 16.7%
medium use	9 14.1%	15 22.7%
low use	17 26.6%	17 25.8%
high use	12 18.8%	10 15.2%
medium use	9 14.1%	16 24.2%
low use	17 26.6%	17 25.8%
high use	13 20.3%	13 19.7%
medium use	7 10.9%	15 22.7%
low use	18 28.1%	15 22.7%
high use	14 21.9%	13 19.7%
medium use	5 7.8%	13 19.7%
low use	17 26.6%	15 22.7%
high use	15 23.4%	14 21.2%
medium use	5 7.8%	12 18.2%
low use	16 25%	11 16.7%
high use	17 26.6%	15 22.7%
medium use	3 4.7%	11 16.7%
low use	14 21.9%	11 16.7%

Adverse Events

Time Frame	over 12 weeks of study or length of participation
Arm/Group Title	Placebo		Quetiapine
Arm/Group Description	Placebo medication Placebo: placebo capsules		Quetiapine treatment Quetiapine: Quetiapine pharmacotherapy for cannabis dependence
All Cause Mortality
	Placebo		Quetiapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/64 (0%)		0/66 (0%)
Serious Adverse Events
	Placebo		Quetiapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/64 (0%)		0/66 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Quetiapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/64 (53.1%)		46/66 (69.7%)
Cardiac disorders
Hypertension	24/64 (37.5%)	24	36/66 (54.5%)	36
Endocrine disorders
Dyslipidemia	11/64 (17.2%)	11	10/66 (15.2%)	10
General disorders
Hyperglycemia	15/64 (23.4%)	15	18/66 (27.3%)	18
drowsiness	3/64 (4.7%)	3	8/66 (12.1%)	8

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.