An Assessment of the Safety of Varenicline in Methamphetamine-dependent Volunteers
Condition: Methamphetamine Addiction; Crystal Meth Addiction; Amphetamine Addiction
MeSH terms: Amphetamine-Related Disorders; Behavior, Addictive
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Varenicline, then placebo; Placebo, then varenicline
Intervention type(s): Drug; Drug
Intervention description(s): 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; 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
Other intervention name(s): varenicline; placebo
Intervention MeSH terms: Varenicline
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: methamphetamine; varenicline; Chantix; stimulant; crystal meth