Varenicline for Methamphetamine Dependence
|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|
- 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.
- 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
- 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.
|Study Start Date:||February 2012|
|Study Completion Date:||August 2014|
|Primary Completion Date:||August 2014 (Final data collection date for primary outcome measure)|
Placebo Comparator: Sugar pill
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
Varenicline (Chantix (R))
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
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01365819
|United States, California|
|UCLA Vine Street Clinic|
|Los Angeles, California, United States, 90036|
|Principal Investigator:||Steven Shoptaw, PhD||UCLA DGSOM Dept Of Family Medicine|