Varenicline for Methamphetamine Dependence

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Steve Shoptaw, University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT01365819
First received: May 31, 2011
Last updated: June 3, 2014
Last verified: June 2014
  Purpose

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 Intervention Phase
Methamphetamine Dependence
Substance Abuse
Methamphetamine Abuse
Drug: Varenicline
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Varenicline for Methamphetamine Dependence: Phase II Clinical Trial

Resource links provided by NLM:


Further study details as provided by University of California, Los Angeles:

Primary Outcome Measures:
  • Reduction in days methamphetamine is used [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    The primary analysis will compare reductions in MA use days, as well as MA use overall, among participants randomly assigned to receive varenicline versus those randomly assigned to receive placebo.


Secondary Outcome Measures:
  • Number of days retained in trial [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    Secondary aims will compare treatment retention, MA withdrawal symptoms, cognitive function, and cigarette smoking among participants randomly assigned to receive varenicline or placebo


Other Outcome Measures:
  • Delayed time to relapse [ Time Frame: 7 weeks ] [ Designated as safety issue: No ]
    1) To determine whether varenicline reduces MA use and delays time to MA relapse more than placebo among MA dependent participants during the outpatient treatment period.

  • Reduced MA withdrawal symptoms [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    2) To determine whether varenicline reduces MA withdrawal symptoms more than placebo among MA- dependent participants over the course of the trial.

  • Reduction in cigarette smoking [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    3) To determine whether varenicline reduces cigarette smoking more than placebo among cigarette smoking MA dependent participants.


Estimated Enrollment: 100
Study Start Date: February 2012
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Chantix

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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Exclusion Criteria:

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  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01365819

Locations
United States, California
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
  More Information

Publications:
Responsible Party: Steve Shoptaw, Professor, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT01365819     History of Changes
Other Study ID Numbers: Shoptaw_varen2011
Study First Received: May 31, 2011
Last Updated: June 3, 2014
Health Authority: United States: Data and Safety Monitoring Board
United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of California, Los Angeles:
Crystal meth dependence
crystal meth
methamphetamine dependence
substance abuse

Additional relevant MeSH terms:
Methamphetamine
Varenicline
Adrenergic Agents
Adrenergic Uptake Inhibitors
Autonomic Agents
Central Nervous System Agents
Central Nervous System Stimulants
Cholinergic Agents
Cholinergic Agonists
Dopamine Agents
Dopamine Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Nicotinic Agonists
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sympathomimetics
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014