Varenicline for Methamphetamine Dependence

NCT ID: NCT01365819

Last Updated: 2018-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2014-08-31

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.

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.

Conditions

Methamphetamine Dependence; Substance Abuse; Methamphetamine Abuse

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Sugar pill

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Varenicline (Chantix (R))

Group Type: EXPERIMENTAL

Varenicline

Intervention Type: DRUG

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).

Interventions

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).

Intervention Type: 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).

Intervention Type: DRUG

Other Intervention Names

Chantix; Sugar pill

Eligibility Criteria

Inclusion Criteria

Contact site for additional information.

Exclusion Criteria

Contact site for additional information.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Steve Shoptaw

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Steven Shoptaw, PhD

Role: PRINCIPAL_INVESTIGATOR

UCLA DGSOM Dept Of Family Medicine

Locations

UCLA Vine Street Clinic

Los Angeles, California, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 27186086 (View on PubMed)

Briones M, Shoptaw S, Cook R, Worley M, Swanson AN, Moody DE, Fang WB, Tsuang J, Furst B, Heinzerling K. Varenicline treatment for methamphetamine dependence: A randomized, double-blind phase II clinical trial. Drug Alcohol Depend. 2018 Aug 1;189:30-36. doi: 10.1016/j.drugalcdep.2018.04.023. Epub 2018 May 25.

Reference Type: RESULT

PMID: 29860057 (View on PubMed)

Other Identifiers

Shoptaw_varen2011

Identifier Type: -

Identifier Source: org_study_id