Clinical trial NCT00713479
Conditions: Methamphetamine Addiction Crystal Meth Addiction Amphetamine Addiction
Keywords: methamphetamine varenicline Chantix stimulant crystal meth
Sponsor: University of California, Los Angeles
Start date: 2008-07-01; Completion date: 2009-09-01
Enrollment: 8 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
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 of MA in MA-dependent volunteers treated with varenicline and placebo.

Detailed description:
Study Procedures:

Study participants are those who meet 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-component 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 (placebo or varenicline) for the second component 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.

On the first day of the inpatient procedure, subjects received 10 3mg infusions of methamphetamine over 2.5 hours for assessment of drug tolerability. On day 9 of the first component and day 7 of the second component, subjects received either 10 3mg infusions of saline OR methamphetamine over 2.5 hours. In the afternoon, the infusion was the opposite of the morning condition.

Arms: arm 1: Sugar pill (placebo) drug dosing will begin at 0.5 mg once daily for the first 3 days of condition and will be increased to 0.5 mg twice daily for days 5-6 of this condition, and increased to 1 mg twice daily on days 7-10 of this condition. arm 2: Varenicline dosing will begin at 0.5 mg once daily for the first 3 days of condition and will be increased to 0.5 mg twice daily for days 5-6 of this condition, and increased to 1 mg twice daily on days 7-10 of this condition.
Interventions: intervention 1: Varenicline, then placebo intervention 2: Placebo, then varenicline
Intervention descriptions: intervention 1: Subjects receive MA infusions on certain days first under varenicline (10 days) then under placebo (8 days) after a 14-24 day washout in order to determine study medication safety and tolerability intervention 2: Subjects receive MA infusions on certain days first under placebo (10 days) then under varenicline(8 days) after a 14-28 day washout in order to determine study medication safety and tolerability

Protocol documents: