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An Assessment of the Safety of Varenicline in Methamphetamine-Dependent Volunteers
This study is currently recruiting participants.
Verified by National Institute on Drug Abuse (NIDA), January 2009
First Received: July 10, 2008   Last Updated: January 30, 2009   History of Changes
Sponsored by: National Institute on Drug Abuse (NIDA)
Information provided by: National Institute on Drug Abuse (NIDA)
ClinicalTrials.gov Identifier: NCT00713479
  Purpose

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.


Condition Intervention Phase
Behavior
Addictive
Drug: Varenicline
Drug: Placebo
Phase I

Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Safety Study
Official Title: A Human Laboratory Assessment of the Safety and Potential Efficacy of Varenicline in Methamphetamine-Dependent Volunteers Receiving Methamphetamine

Resource links provided by NLM:


Further study details as provided by National Institute on Drug Abuse (NIDA):

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 13
Study Start Date: July 2008
Estimated Study Completion Date: September 2008
Estimated Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm 2: Placebo Comparator Drug: Placebo
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.
Arm 1: Active Comparator Drug: Varenicline
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.

Detailed Description:

Study Procedures:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00713479

Contacts
Contact: Todd Zorick, MD 888-791-9988 TZorick@mednet.ucla.edu
Contact: Thomas Hanson, MA 888-791-9988 THanson@mednet.ucla.edu

Locations
United States, California
UCLA NPI Recruiting
Los Angeles, California, United States, 90095
Sponsors and Collaborators
Investigators
Principal Investigator: Edythe D London, PhD UCLA NPI
  More Information

No publications provided

Responsible Party: UCLA Dept of Family Medicine ( Steven Shoptaw, PhD )
Study ID Numbers: 18185-PI-EDL-V
Study First Received: July 10, 2008
Last Updated: January 30, 2009
ClinicalTrials.gov Identifier: NCT00713479     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute on Drug Abuse (NIDA):
methamphetamine
varenicline
Chantix
stimulant

Study placed in the following topic categories:
Dopamine Uptake Inhibitors
Neurotransmitter Agents
Methamphetamine
Dopamine
Adrenergic Agents
Central Nervous System Stimulants
Dopamine Agents
Amphetamine
Peripheral Nervous System Agents
Varenicline

Additional relevant MeSH terms:
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Uptake Inhibitors
Sympathomimetics
Physiological Effects of Drugs
Central Nervous System Stimulants
Pharmacologic Actions
Methamphetamine
Autonomic Agents
Therapeutic Uses
Amphetamine
Dopamine Agents
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 03, 2009