GUAN: Open-Label Pilot Study of Guanfacine-Extended Release for the Treatment of Cannabis Dependence

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01467999
• Collaborator: (none)
• Enrollment: 22
• Location: 1
• Arm: 1
• Duration (Months): 56
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether guanfacine represents a tolerable, potentially effective pharmacotherapy option for cannabis dependence. Interested in seeing whether guanfacine treatment reduces marijuana consumption, withdrawal symptoms, and craving as compared to baseline.

Condition or Disease	Intervention/Treatment	Phase
Cannabis Dependence	Drug: Guanfacine	Phase 1

Detailed Description

Cannabis use disorders remain the most common illicit drug use disorder and options for treatment remain limited. Compared to other abusable substances, there has been little investigation of pharmacotherapies for cannabis dependence and no effective pharmacotherapy for cannabis dependence has been developed yet. As such, the development of effective cannabis dependence pharmacotherapy is an important unmet public health need. Lofexidine, an alpha-2 agonist, is effective in treating opioid withdrawal and shows promise as cannabis use disorder pharmacotherapy, though its use may be limited by a cumbersome (thrice daily) dosing regimen. An alpha-2-agonist with a longer half-life, such as guanfacine, may have some of the same benefits as lofexidine at comparable doses, but its easier (once daily) dosing regimen may promote compliance and treatment retention. The purpose of this study is therefore to determine whether guanfacine represents a tolerable, potentially effective pharmacotherapy option for cannabis dependence. This pilot study can also provide the basis for subsequently conducting a larger study aimed at determining efficacy with the appropriate randomized, placebo-controlled design.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-Label Pilot Study of Guanfacine-Extended Release for the Treatment of Cannabis Dependence
• Study Start Date: Feb 1, 2012
• Actual Primary Completion Date: Apr 1, 2016
• Actual Study Completion Date: Oct 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Guanfacine Guanfacine, 4mg given once daily	Drug: Guanfacine; Guanfacine, 4mg given once daily; Other Names: Intuniv

Outcome Measures

Primary Outcome Measures

1. Reduction in Mean Number of Days of Cannabis Use Per Week [Daily cannabis use reported during the 8 week trial or the length of the patient's participation]

   The reduction in cannabis consumption quantified by the number of days of cannabis use per week was assessed, as measured by the Time Line followback, reported week 1 compared to week 8.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Men and women between the ages of 18-60 who meet DSM-IV criteria for current marijuana dependence

• Individuals must report using marijuana at least 20 days in the past 30 days and have a positive urine test for THC on the day of study entry.

• Individual must describe marijuana as their primary drug of abuse.

• Individuals must be capable of giving informed consent and capable of complying with study procedures.

Exclusion Criteria:

• Meets DSM-IV-TR criteria for schizophrenia, schizoaffective illness, psychotic disorder other than transient psychosis due to drug abuse, major depression, bipolar illness or psychiatric disorders (other than substance abuse) which require psychiatric intervention.

• Unstable medication conditions, such as poorly controlled diabetes or hypertension (>140/90 mmHg), which might make participation hazardous.

• Individuals with liver enzyme function tests greater than three times normal, or acute hepatitis

• Individuals with a history of a seizure disorder

• Individuals with current suicidal risk.

• Individuals who are cognitively impaired

• Bradycardia (< 50 beats/minute), hypotension (sitting or standing BP < 90/50), or symptoms attributable to low BP (i.e. lightheadedness or dizziness on standing).

• Nursing mothers and pregnant women. Women of child bearing age will be included in the study provided that they are not pregnant, based on the results of a blood pregnancy test drawn at the time of screening. They must also agree to use a method of contraception with proven efficacy and agree not to become pregnant during the study. To confirm this, urine pregnancy tests will be repeated monthly. Women will be provided a full explanation of the potential dangers of pregnancy while on the study medication. If a woman becomes pregnant, the study medication will be discontinued.

• Individuals who are physiologically dependent on any other drugs (excluding nicotine) that would require a medical intervention

• Individuals with known sensitivity to alpha-2 Agonists

• Individuals with coronary vascular disease as indicated by history or suspected by abnormal ECG or history of cardiac symptoms

• Individuals currently being treated with antihypertensive medication, including alpha-2 agonists

• Individuals currently taking medications that may interact adversely with guanfacine.

• Individuals who are court-mandated to treatment.

Contacts and Locations

Locations

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

Sponsors and Collaborators

• New York State Psychiatric Institute

Investigators

• Principal Investigator: Frances Levin, M.D., Columbia University
• Principal Investigator: Elias Dakwar, M.D., Columbia University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Frances R Levin, Director of Substance Use Disorder, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT01467999
• Other Study ID Numbers: #6393; 6393
• First Posted: Nov 9, 2011
• Last Update Posted: Feb 5, 2019
• Last Verified: Jan 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Frances R Levin, Director of Substance Use Disorder, New York State Psychiatric Institute: cannabis dependence; marijuana dependence; guanfacine
• Additional relevant MeSH terms: Marijuana Abuse; Guanfacine

Study Results

Participant Flow

Recruitment Details	Participants responded to newspapers, radio and public service announcements in the New York City area, and reported at least 20 days of use in the past 30 days.

Arm/Group Title	Guanfacine
Arm/Group Description	Guanfacine, 4mg given once daily Guanfacine: Guanfacine, 4mg given once daily
Period Title: Overall Study
STARTED	22
COMPLETED	9
NOT COMPLETED	13

Baseline Characteristics

Arm/Group Title	Guanfacine
Arm/Group Description	Guanfacine, 4mg given once daily Guanfacine: Guanfacine, 4mg given once daily
Overall Participants	22
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.1 (10.3)
Sex: Female, Male (Count of Participants)
Female	8 36.4%
Male	14 63.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 9.1%
Not Hispanic or Latino	20 90.9%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	4 18.2%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 22.7%
White	5 22.7%
More than one race	6 27.3%
Unknown or Not Reported	2 9.1%

Outcome Measures

1. Primary Outcome

Title	Reduction in Mean Number of Days of Cannabis Use Per Week
Description	The reduction in cannabis consumption quantified by the number of days of cannabis use per week was assessed, as measured by the Time Line followback, reported week 1 compared to week 8.
Time Frame	Daily cannabis use reported during the 8 week trial or the length of the patient's participation

Outcome Measure Data

Analysis Population Description

intent-to-treat sample

Arm/Group Title	Guanfacine
Arm/Group Description	Guanfacine, 4mg given once daily Guanfacine: Guanfacine, 4mg given once daily
Measure Participants	22
week 1	4.1 (0.6)
week 8	3.1 (0.9)

Adverse Events

Time Frame	during 8 weeks of open label participation
Arm/Group Title	Guanfacine
Arm/Group Description	Guanfacine, 4mg given once daily Guanfacine: Guanfacine, 4mg given once daily
All Cause Mortality
	Guanfacine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Guanfacine
	Affected / at Risk (%)	# Events
Total	0/22 (0%)
Other (Not Including Serious) Adverse Events
	Guanfacine
	Affected / at Risk (%)	# Events
Total	14/22 (63.6%)
Cardiac disorders
hypotension	3/22 (13.6%)	3
Gastrointestinal disorders
constipation	2/22 (9.1%)	2
nausea	3/22 (13.6%)	3
General disorders
drowsiness	3/22 (13.6%)	3
dry mouth	5/22 (22.7%)	5
fatigue	5/22 (22.7%)	5
headache	1/22 (4.5%)	1
increased urination	1/22 (4.5%)	1
insomnia	5/22 (22.7%)	5
lightheadedness	4/22 (18.2%)	4

Limitations/Caveats

Due to its open-label nature, it is not possible to determine whether the reductions in cannabis use were due to study drug, or whether they were related to other study procedures.

More Information

Certain Agreements

Principal Investigators are NOT 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.