An Assessment of the Safety of Varenicline in Methamphetamine-dependent Volunteers
More people worldwide use amphetamine-type stimulants than any illicit drug besides cannabis, and methamphetamine (MA) abuse and dependence is the fastest growing drug problem in the United States. Much work remains in identifying an effective pharmacotherapy for MA dependence. The neurobiological actions produced by MA involve dopamine (DA), serotonin, and norepinephrine, but also include alterations to cholinergic neurotransmitter systems. Candidate compounds that target acetylcholine (ACh) are attractive options for development that have not received adequate attention. Varenicline is a drug that increases the release of DA in the brain and it is logical to assume that it would to some extent compensate for the reduction in these neurotransmitters that occurs in MA withdrawal.
Current research has linked certain genes that are related to neurotransmitters with drug abuse and memory impairment (e.g., A1 allele for the D2 dopamine receptor and catechol-O-methyltransferase). We will take blood samples and test for these genes in order to relate the findings to brain function.
This is a double-blind, placebo-controlled, within-subjects study to determine the safety and tolerability, and subjective and reinforcing effects of MA in MA-dependent volunteers treated with varenicline and placebo.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Human Laboratory Assessment of the Safety and Potential Efficacy of Varenicline in Methamphetamine-dependent Volunteers Receiving Methamphetamine|
- The safety of MA administration during treatment with varenicline will be assessed by reporting of adverse events (AEs), and using EKG recording, and heart rate and blood pressure measurements. [ Time Frame: Hourly ] [ Designated as safety issue: Yes ]
- Efficacy will be assessed by measuring effects of varenicline treatment on subjective and reinforcing effects produced by administration of MA and craving produced by exposure to drug cues. [ Time Frame: Daily ] [ Designated as safety issue: No ]
|Study Start Date:||July 2008|
|Study Completion Date:||September 2009|
|Primary Completion Date:||August 2009 (Final data collection date for primary outcome measure)|
|Placebo Comparator: Arm 2||
Placebo dosing will begin at 0.5 mg once daily for the first 3 days and will be increased to 0.5 mg twice daily for the days 5-6, and increased to 1 mg once daily on days 7-10.
|Active Comparator: Arm 1||
Varenicline dosing will begin at 0.5 mg once daily for the first 3 days and will be increased to 0.5 mg twice daily for the days 5-6, and increased to 1 mg once daily on days 7-10.
Other Name: Chantix
This study will enroll 13 participants meeting criteria for MA dependence who are not seeking treatment, and who also meet criteria for nicotine dependence. Participants will be asked to wear a telemetry device during screening and throughout the study that records heart rate and body temperature. Participants will be required to refrain from smoking at certain times, illicit and prescription drug use for the duration of the study and this will be confirmed with daily urine testing.
The study consists of 30 days or less of outpatient screening. The 2-phase inpatient portion of the study lasts a total of 18 days. Participants will be admitted to the GCRC at UCLA for Days 1-10. After the first study day, participants will be randomized to varenicline or matched placebo for 9-days and then discharged from the GCRC. Then, after 2-4 weeks, the same subjects return to the GCRC to be switched to the alternate condition for the second phase of the study, which lasts another 8-days. Each subject is randomized to both varenicline and placebo, so total time commitment is 18 inpatient study days. One follow-up visit is scheduled 2 weeks after completion of both study phases for assessment of delayed adverse events and for final payment.
|United States, California|
|Los Angeles, California, United States, 90095|
|Principal Investigator:||Edythe D London, PhD||UCLA NPI|