An Assessment of the Safety of Varenicline in Methamphetamine-dependent Volunteers

• Status: Completed
• Trial end date: 2009-09-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, Los Angeles
• Collaborator: National Institute on Drug Abuse (NIDA)
• Treatments: Methamphetamine; Varenicline

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.