Varenicline for Methamphetamine Dependence

• Sponsor: University of California, Los Angeles (Other)
• Overall Status: Completed
• CT.gov ID: NCT01365819
• Collaborator: (none)
• Enrollment: 52
• Location: 1
• Arms: 2
• Duration (Months): 30
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

Methamphetamine (MA) dependence is a source of continuing danger for both individuals and society. While there are some behavioral treatments, they are not always effective. To date, there are no medications available to treatment methamphetamine dependence. There is some early evidence suggesting that varenicline (also known as Chantix(tm)) may help people to stop or reduce their use of methamphetamine. Varenicline is already on the market in the U.S. for cigarette smoking cessation and shows promise for treating alcohol dependence. In order to determine if varenicline can help people stop using methamphetamine, we will enroll 90 methamphetamine-dependent people who are looking for treatment into the study at the UCLA Vine Street Clinic operated by Dr Shoptaw of UCLA. Half will receive varenicline (n=45) and half will receive placebo (n=45) which will be determined randomly. Everyone will receive talk therapy for methamphetamine dependence. People will take the medication for 9 weeks followed by a 4 week follow-up period. Before receiving any medication, participants will complete a maximum 2 week (6 study visits) lead-in to complete baseline assessments, psychological and medical evaluation, and comprehensive assessment of drug use to determine study eligibility. If a person is eligible for the study, s/he will receive either varenicline or placebo. Participants will visit the UCLA Vine Street Clinic (UCLA VSC) three times a week study visits. At the end of the medication phase, subjects will complete a four week follow up period for safety monitoring.

Condition or Disease	Intervention/Treatment	Phase
Methamphetamine Dependence; Substance Abuse; Methamphetamine Abuse	Drug: Varenicline; Drug: Placebo	Phase 2

Detailed Description

Methamphetamine (MA) dependence is a significant source of deleterious consequences to individual and public health including HIV infection, psychological distress, and cardiovascular disease. Behavioral treatments, including cognitive behavioral therapy and contingency management are available, but are modestly effective. Although pharmacotherapy may improve treatment outcomes, ten years of randomized, placebo-controlled trials of medications for MA dependence have failed to identify a medication with a robust effect in generalized populations of MA users.

Cholinergic mechanisms are important in the neurobiology of MA dependence. Varenicline is a α4β2 nicotinic receptor partial agonist and α7 nicotinic receptor full agonist that is approved for cigarette smoking cessation and shows promise for treating alcohol dependence. Varenicline may be effective for the treatment of MA dependence due to: (1) restoration of MA-related dopaminergic deficits via binding to α4β2 receptors in striatal dopaminergic (DA) neurons, (2) reductions in cigarette smoking and the associated nicotine-mediated potentiation of MA effects, (3) activation of the nicotinic cholinergic systems that mediate reductions in reinstatement of MA seeking seen with cannabinoid receptor antagonists and acetylcholinesterase inhibitors, (4) relief of MA-related glutamatergic deficits via α7 nicotinic acetylcholine (ACh) receptor activation, and (5) reduction in MA-related cognitive dysfunction via the cognitive enhancing effects of cholinergic agonists.

The investigators will enroll 90 treatment seeking, MA-dependent participants who will be randomly assigned to receive varenicline (n=45) or placebo (n=45), in conjunction with cognitive behavioral therapy (CBT) for 9 weeks followed by a 4 week follow-up period. Prior to enrollment in the trial, participants will complete a maximum 2 week (6 study visits) lead-in to complete baseline assessments, psychological and medical evaluation, and comprehensive assessment of drug use to determine study eligibility. Once determined to be eligible for the trial, participants will be randomly assigned to varenicline or placebo and will start study medication. Similar to smoking cessation treatment, participants will undergo dose escalation to varenicline 1 mg BID (or placebo BID) over one week as outpatients. Participants will have regular clinic visits at the UCLA Vine Street Clinic (UCLA VSC) for thrice-weekly study visits. At the end of the medication phase, subjects will complete a four-week follow up period for safety monitoring.

Study Design

• Study Type: Interventional
• Actual Enrollment: 52 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Varenicline for Methamphetamine Dependence: Phase II Clinical Trial
• Study Start Date: Feb 1, 2012
• Actual Primary Completion Date: Aug 1, 2014
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Sugar pill Placebo	Drug: Placebo; Placebo dose will start at 0.5 mg (sugar pill) daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 9).; Other Names: Sugar pill
Experimental: Varenicline Varenicline (Chantix (R))	Drug: Varenicline; Varenicline dosing will follow that which has been shown to be effective for cigarette smoking cessation. Varenicline dose will start at 0.5 mg daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 9).; Other Names: Chantix

Outcome Measures

Primary Outcome Measures

1. End of Treatment Abstinence [9 weeks]

   The primary analysis will compare two weeks continuous MA abstinence at end of treatment during weeks 8 and 9 among participants randomly assigned to receive varenicline versus those randomly assigned to receive placebo.

Secondary Outcome Measures

1. Number of Days Retained in Trial [9 weeks]

   Secondary aims will compare treatment retention among participants randomly assigned to receive varenicline or placebo

Other Outcome Measures

1. Prevalence of Relapse Following Initiation of Abstinence During Treatment [7 weeks]

   1) The number of participants who achieve MA abstinence and subsequently relapse to MA use during treatment by condition (varenicline, placebo) during the outpatient treatment period.

2. Reduced MA Withdrawal Symptoms [9 weeks]

   2) To determine whether varenicline reduces MA withdrawal symptoms more than placebo among MA- dependent participants over the course of the trial.

3. Reduction in Cigarette Smoking [9 weeks]

   3) To determine whether varenicline reduces cigarette smoking more than placebo among cigarette smoking MA dependent participants.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Contact site for additional information.

Exclusion Criteria:

Contact site for additional information.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Vine Street Clinic	Los Angeles	California	United States	90036

Sponsors and Collaborators

• University of California, Los Angeles

Investigators

• Principal Investigator: Steven Shoptaw, PhD, UCLA DGSOM Dept Of Family Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

• Zorick T, Sevak RJ, Miotto K, Shoptaw S, Swanson AN, Clement C, De La Garza R 2nd, Newton TF, London ED. Pilot safety evaluation of varenicline for the treatment of methamphetamine dependence. J Exp Pharmacol. 2009 Dec 24;2:13-8. eCollection 2010.

• Responsible Party: Steve Shoptaw, Professor, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT01365819
• Other Study ID Numbers: Shoptaw_varen2011
• First Posted: Jun 3, 2011
• Last Update Posted: Jan 18, 2018
• Last Verified: Jan 1, 2018

• Keywords provided by Steve Shoptaw, Professor, University of California, Los Angeles: Crystal meth dependence; crystal meth; methamphetamine dependence; substance abuse
• Additional relevant MeSH terms: Substance-Related Disorders; Varenicline

Study Results

Participant Flow

Arm/Group Title	Sugar Pill	Varenicline
Arm/Group Description	Placebo Placebo: Placebo dose will start at 0.5 mg (sugar pill) daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 9).	Varenicline (Chantix (R)) Varenicline: Varenicline dosing will follow that which has been shown to be effective for cigarette smoking cessation. Varenicline dose will start at 0.5 mg daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 9).
Period Title: Overall Study
STARTED	25	27
COMPLETED	12	14
NOT COMPLETED	13	13

Baseline Characteristics

Arm/Group Title	Sugar Pill	Varenicline	Total
Arm/Group Description	Placebo Placebo: Placebo dose will start at 0.5 mg (sugar pill) daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 9).	Varenicline (Chantix (R)) Varenicline: Varenicline dosing will follow that which has been shown to be effective for cigarette smoking cessation. Varenicline dose will start at 0.5 mg daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 9).	Total of all reporting groups
Overall Participants	25	27	52
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	25 100%	27 100%	52 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	9 36%	10 37%	19 36.5%
Male	16 64%	17 63%	33 63.5%

Outcome Measures

1. Primary Outcome

Title	End of Treatment Abstinence
Description	The primary analysis will compare two weeks continuous MA abstinence at end of treatment during weeks 8 and 9 among participants randomly assigned to receive varenicline versus those randomly assigned to receive placebo.
Time Frame	9 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sugar Pill	Varenicline
Arm/Group Description	Placebo Placebo: Placebo dose will start at 0.5 mg (sugar pill) daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 9).	Varenicline (Chantix (R)) Varenicline: Varenicline dosing will follow that which has been shown to be effective for cigarette smoking cessation. Varenicline dose will start at 0.5 mg daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 9).
Measure Participants	25	27
Count of Participants [Participants]	5 20%	4 14.8%

2. Secondary Outcome

Title	Number of Days Retained in Trial
Description	Secondary aims will compare treatment retention among participants randomly assigned to receive varenicline or placebo
Time Frame	9 weeks

Outcome Measure Data

Analysis Population Description

This outcome was not assessed.

Arm/Group Title	Sugar Pill	Varenicline
Arm/Group Description	Placebo Placebo: Placebo dose will start at 0.5 mg (sugar pill) daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 9).	Varenicline (Chantix (R)) Varenicline: Varenicline dosing will follow that which has been shown to be effective for cigarette smoking cessation. Varenicline dose will start at 0.5 mg daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 9).
Measure Participants	0	0

3. Other Pre-specified Outcome

Title	Prevalence of Relapse Following Initiation of Abstinence During Treatment
Description	1) The number of participants who achieve MA abstinence and subsequently relapse to MA use during treatment by condition (varenicline, placebo) during the outpatient treatment period.
Time Frame	7 weeks

Outcome Measure Data

Analysis Population Description

This analysis presents the number of participants in each condition who achieved abstinence during treatment and later relapsed.

Arm/Group Title	Sugar Pill	Varenicline
Arm/Group Description	Placebo Placebo: Placebo dose will start at 0.5 mg (sugar pill) daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 9).	Varenicline (Chantix (R)) Varenicline: Varenicline dosing will follow that which has been shown to be effective for cigarette smoking cessation. Varenicline dose will start at 0.5 mg daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 9).
Measure Participants	14	13
Count of Participants [Participants]	6 24%	8 29.6%

4. Other Pre-specified Outcome

Title	Reduced MA Withdrawal Symptoms
Description	2) To determine whether varenicline reduces MA withdrawal symptoms more than placebo among MA- dependent participants over the course of the trial.
Time Frame	9 weeks

Outcome Measure Data

Analysis Population Description

This outcome was not assessed.

Arm/Group Title	Sugar Pill	Varenicline
Arm/Group Description	Placebo Placebo: Placebo dose will start at 0.5 mg (sugar pill) daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 9).	Varenicline (Chantix (R)) Varenicline: Varenicline dosing will follow that which has been shown to be effective for cigarette smoking cessation. Varenicline dose will start at 0.5 mg daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 9).
Measure Participants	0	0

5. Other Pre-specified Outcome

Title	Reduction in Cigarette Smoking
Description	3) To determine whether varenicline reduces cigarette smoking more than placebo among cigarette smoking MA dependent participants.
Time Frame	9 weeks

Outcome Measure Data

Analysis Population Description

This analysis includes a sub-population of participants in both conditions who smoked any cigarettes during treatment. Results are model fitted number of cigarettes smoked per week at baseline and at week 9.

Arm/Group Title	Sugar Pill	Varenicline
Arm/Group Description	Placebo Placebo: Placebo dose will start at 0.5 mg (sugar pill) daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 9).	Varenicline (Chantix (R)) Varenicline: Varenicline dosing will follow that which has been shown to be effective for cigarette smoking cessation. Varenicline dose will start at 0.5 mg daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 9).
Measure Participants	20	15
Measure average number of cigarettes	37	42
Mean (Standard Deviation) [average number of cigarettes]	19 (20)	1 (3)

Adverse Events

Time Frame	Adverse event data were collected during the course of the clinical trial, which included 2 weeks of screening, 9 weeks of medication and 4 weeks of follow-up.
Arm/Group Title	Sugar Pill		Varenicline
Arm/Group Description	Placebo Placebo: Placebo dose will start at 0.5 mg (sugar pill) daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 9).		Varenicline (Chantix (R)) Varenicline: Varenicline dosing will follow that which has been shown to be effective for cigarette smoking cessation. Varenicline dose will start at 0.5 mg daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 9).
All Cause Mortality
	Sugar Pill		Varenicline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sugar Pill		Varenicline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/27 (0%)
Other (Not Including Serious) Adverse Events
	Sugar Pill		Varenicline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/25 (68%)		21/27 (77.8%)
Gastrointestinal disorders
Nausea	5/25 (20%)	6	10/27 (37%)	13
Nervous system disorders
Headache	7/25 (28%)	9	10/27 (37%)	15
Psychiatric disorders
Insomnia	5/25 (20%)	7	9/27 (33.3%)	11
Vivid dreams	5/25 (20%)	7	12/27 (44.4%)	15

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.