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
Intervention: Varenicline, then placebo; Placebo, then varenicline
Intervention description: 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
Intervention MeSH terms: Varenicline
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: methamphetamine; varenicline; Chantix; stimulant; crystal meth

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Be English-speaking volunteers who are not seeking treatment at the time of the study;

          2. Be between 18-55 years of age;

          3. Meet DSM-IV TR criteria for MA dependence;

          4. Must be cigarette smokers, defined as smoking 10 or more cigarettes per day by
             self-report;

          5. Have a self-reported history of using MA by the smoked or IV route and provide at
             least one MA-positive urine prior to admission;

          6. Have vital signs as follows: resting pulse between 50 and 90 bpm, blood pressures
             between 105-150 mm Hg systolic and 45-90 mm Hg diastolic; this criterion must be met
             within 2 days of admission;

          7. Have hematology and chemistry laboratory tests that are within normal (+/- 10%) limits
             with the following exceptions: a) liver function tests (total bilirubin, ALT, AST, and
             alkaline phosphatase) < 3 x the upper limit of normal, and b) kidney function tests
             (creatinine and BUN) < 2 x the upper limit of normal;

          8. Have a baseline EKG that demonstrates normal sinus rhythm, normal conduction
             (including QTc), and no clinically significant arrhythmias;

          9. Have a medical history and brief physical examination demonstrating no clinically
             significant contraindications for study participation, in the judgment of the
             admitting physician or nurse practitioner and the principal investigator.

        Exclusion Criteria:

          1. Have any history or evidence suggestive of seizure disorder or brain injury

          2. Have any previous medically adverse reaction to MA, including loss of consciousness,
             chest pain, or epileptic seizure

          3. Have neurological or psychiatric disorders, such as

               -  psychosis, bipolar illness or major depression as assessed by SCID;

               -  organic brain disease or dementia assessed by clinical interview;

               -  history of any psychiatric disorder which would require ongoing treatment or
                  which would make study compliance difficult;

               -  history of suicide attempts within the past three months assessed by SCID and/or
                  current suicidal ideation/plan as assessed by SCID;

          4. Have evidence of clinically significant heart disease or hypertension, as determined
             by the PI;

          5. Have a family history in first-degree relatives of early cardiovascular morbidity or
             mortality, as determined by the PI;

          6. Have evidence of untreated or unstable medical illness including: neuroendocrine,
             autoimmune, renal, hepatic, or active infectious disease;

          7. Have HIV and are currently symptomatic, have a diagnosis of AIDS, or are receiving
             antiretroviral medication;

          8. Be pregnant or nursing. Other females must either be unable to conceive (i.e.,
             surgically sterilized, sterile, or post-menopausal) or be using a reliable form of
             contraception (e.g., abstinence, birth control pills, intrauterine device, condoms, or
             spermicide). All females must provide negative pregnancy urine tests before study
             entry, upon hospital admission, and at the end of study participation;

          9. Have asthma or currently use alpha or beta agonists, theophylline, or other
             sympathomimetics;

         10. Have any other illness, condition, or use of psychotropic medications, which in the
             opinion of the PI and/or the admitting physician or nurse practitioner would preclude
             safe and/or successful completion of the study.