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

NCT00713479 | Completed Phase 1 Results DMC

• 3 other identifiers: 18185-PI-EDL-VP50DA018185DPMC
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Methamphetamine Addiction; Crystal Meth Addiction; Amphetamine Addiction

Keywords

methamphetamine; varenicline; Chantix; stimulant; crystal meth

Outcome Measures

Primary Outcomes (3)

• Systolic Blood Pressure

  Systolic blood pressure is evaluated at 15 min intervals under placebo or varenicline in the presence of methamphetamine over 140 minutes post infusion. Data is pooled and the mean and standard deviation are presented.

  15 minute intervals

• Diastolic Blood Pressure

  Diastolic blood pressure is evaluated at 15 min intervals under placebo or varenicline in the presence of methamphetamine over 140 minutes post infusion. Data is pooled and the mean and standard deviation are presented.

  15 minute intervals

• Heart Rate

  Heart rate is evaluated at 15 min intervals under placebo or varenicline in the presence of methamphetamine over 140 minutes post infusion. Data is pooled and the mean and standard deviation are presented.

  15 minute intervals

Secondary Outcomes (1)

• Depression

  Daily

Study Arms (2)

Sugar pill

PLACEBO COMPARATOR

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.

Drug: Varenicline, then placebo; Drug: Placebo, then varenicline

Varenicline

ACTIVE COMPARATOR

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.

Drug: Varenicline, then placebo; Drug: Placebo, then varenicline

Interventions

Varenicline, then placebo DRUG

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

Also known as: varenicline

Sugar pill; Varenicline

Placebo, then varenicline DRUG

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

Also known as: placebo

Sugar pill; Varenicline

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Be English-speaking volunteers who are not seeking treatment at the time of the study;
• Be between 18-55 years of age;
• Meet DSM-IV TR criteria for MA dependence;
• Must be cigarette smokers, defined as smoking 10 or more cigarettes per day by self-report;
• 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;
• 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;
• 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;
• Have a baseline EKG that demonstrates normal sinus rhythm, normal conduction (including QTc), and no clinically significant arrhythmias;
• 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.

You may not qualify if:

• Have any history or evidence suggestive of seizure disorder or brain injury
• Have any previous medically adverse reaction to MA, including loss of consciousness, chest pain, or epileptic seizure
• 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;
• Have evidence of clinically significant heart disease or hypertension, as determined by the PI;
• Have a family history in first-degree relatives of early cardiovascular morbidity or mortality, as determined by the PI;
• Have evidence of untreated or unstable medical illness including: neuroendocrine, autoimmune, renal, hepatic, or active infectious disease;
• Have HIV and are currently symptomatic, have a diagnosis of AIDS, or are receiving antiretroviral medication;
• 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;
• Have asthma or currently use alpha or beta agonists, theophylline, or other sympathomimetics;
• 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.

Sponsors & Collaborators

• University of California, Los Angeles: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

UCLA NPI

Los Angeles, California, 90095, United States

Location

Related Publications (1)

• Zorick T, Sevak RJ, Miotto K, Shoptaw S, Swanson AN, Clement C, De La Garza R 2nd, Newton TF, London ED. Pilot safety evaluation of varenicline for the treatment of methamphetamine dependence. J Exp Pharmacol. 2009 Dec 24;2:13-8. eCollection 2010.

  PMID: 27186086 RESULT

MeSH Terms

Conditions

Amphetamine-Related Disorders

Interventions

Varenicline

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinoxalines

Limitations and Caveats

Small sample size

Results Point of Contact

• Title: Dr Edythe London
• Organization: University of California, Los Angeles

elondon@mednet.ucla.edu

(310) 825-0606

Study Officials

• Edythe D London, PhD

  UCLA NPI

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 10, 2008
• First Posted: July 11, 2008
• Study Start: July 1, 2008
• Primary Completion: August 1, 2009
• Study Completion: September 1, 2009
• Last Updated: March 13, 2018
• Results First Posted: January 27, 2014

Record last verified: 2018-02

Locations

US (1)