Varenicline for Methamphetamine Dependence
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. At day 8, subjects will continue on study medication and be admitted for a brief inpatient detoxification (4 nights) at the Harbor-UCLA or UCLA Clinical and Translational Research Center (CTRC). On the day of inpatient discharge (day 12), participants will go back to the UCLA Vine Street Clinic (UCLA VSC) for 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.
|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|
|Estimated Study Completion Date:||March 2014|
|Estimated Primary Completion Date:||January 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). This intervention will also include a brief inpatient detox (4 nights).
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). This intervention also includes a brief inpatient detox (4 nights).
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. At day 8, subjects will continue on study medication and be admitted for a brief inpatient detoxification (4 nights) at the Harbor-UCLA Clinical and Translational Research Center (CTRC). On the day of inpatient discharge (day 12), participants will resume 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.
|Contact: Stephanie Amaya, BA||323 461 email@example.com|
|Contact: Jackie Benavente, MFT||323 461 firstname.lastname@example.org|
|United States, California|
|UCLA Vine Street Clinic||Recruiting|
|Los Angeles, California, United States, 90036|
|Principal Investigator: Keith Heinzerling, MD MPH|
|Principal Investigator:||Steven Shoptaw, PhD||UCLA DGSOM Dept Of Family Medicine|