Varenicline as a Treatment for Methamphetamine Dependence

NCT01571167 | Completed Phase 1 DMC

• 3 other identifiers: H-26875DPMC1R01DA027134-01
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of the study is to determine the effects of treatment with varenicline (1 and 2 mg daily), compared to treatment with placebo, on methamphetamine-induced craving and subjective effects in methamphetamine-dependent human volunteers.

Conditions

Methamphetamine Dependence; Methamphetamine Abuse; Substance Abuse

Keywords

Methamphetamine; Chantix; Varenicline

Outcome Measures

Primary Outcomes (1)

• The effects of varenicline and methamphetamine on safety and cardiovascular measures

  The safety of MA administration during treatment will be assessed by reporting of adverse events (AEs), and using ECG recording, and heart rate and blood pressure measurements. Digital 12-lead ECG will also be recorded prior to randomization. Blood pressure and heart rate will be measured from 15 min prior to MA or placebo dosing until 2 h after dosing. In addition, heart rate and blood pressure will be assessed throughout the inpatient portion of the protocol.

  On study day 6 and 7

Secondary Outcomes (1)

• The effects of varenicline and methamphetamine on subjective effects

  On study day 6 and 7

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Varenicline 2 mg

ACTIVE COMPARATOR

Drug: Varenicline

Varenicline 1 mg

ACTIVE COMPARATOR

Drug: Varenicline

Interventions

Placebo DRUG

Participants will receive varenicline or matched placebo from day 1 through day 7, then the same subjects will return within 2-4 weeks and assigned to each of the two remaining study medication conditions, and undergo the identical procedures (3-phase study).

Also known as: Sugar pill

Placebo

Varenicline DRUG

For varenicline 1 mg, dosing will begin at 0.5 mg once daily (with 0 mg placebo to maintain blind of bid dosing) for days 1-3, will be increased to 0.5 mg twice daily for the days 4-6, and then reduced to 0.5 mg once daily on day 7. No medication is given on Day 8.

Also known as: Chantix

Varenicline 1 mg

Eligibility Criteria

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

You may qualify if:

• In order to participate in the study, participants must:
• 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:

• Subjects will be excluded if they:
• Have any previous medically adverse reaction to METH, including loss of consciousness, chest pain, or epileptic seizure
• Have neurological or psychiatric disorders, as assessed by MINI, such as: episode of major depression within the past 2 years; lifetime history of schizophrenia, other psychotic illness, or bipolar illness; current organic brain disease or dementia assessed by clinical interview; history of or any current psychiatric disorder which would require ongoing treatment or which would make study compliance difficult; history of suicide attempts within the past three months and/or current suicidal ideation/plan; history of psychosis occurring in the absence of current METH use
• Meet DSM-IV criteria for abuse/dependence on alcohol or other drugs, except nicotine or marijuana
• Have used methamphetamine only by the intravenous route
• Have evidence of clinically significant heart disease or hypertension, as determined by physician
• Have evidence of untreated or unstable medical illness including: neuroendocrine, autoimmune, renal, hepatic, or active infectious disease
• Have HIV and currently symptomatic, have a diagnosis of AIDS, or currently taking 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, and throughout the study
• Have any history of asthma, chronic coughing and wheezing, or other chronic respiratory illnesses
• Currently use alpha or beta agonists, theophylline, or other sympathomimetics
• Have made a suicide attempt in the past year
• Have any other illness, condition, or use of medications, which in the opinion of the PI and/or the admitting physician would preclude safe and/or successful completion of study.
• Criteria for Discontinuation Following Initiation:
• Positive urine drug screen or breath test indicating illicit use of cocaine, MA, alcohol, opiates, or other abused drugs not delivered as part of this protocol

Sponsors & Collaborators

• Baylor College of Medicine: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Michael E. DeBakey Veterans Affairs Medical Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Kalechstein AD, Mahoney JJ 3rd, Verrico CD, De La Garza R 2nd. Short-term, low-dose varenicline administration enhances information processing speed in methamphetamine-dependent users. Neuropharmacology. 2014 Oct;85:493-8. doi: 10.1016/j.neuropharm.2014.05.045. Epub 2014 Jun 12.

  PMID: 24930359 DERIVED

• Verrico CD, Mahoney JJ 3rd, Thompson-Lake DG, Bennett RS, Newton TF, De La Garza R 2nd. Safety and efficacy of varenicline to reduce positive subjective effects produced by methamphetamine in methamphetamine-dependent volunteers. Int J Neuropsychopharmacol. 2014 Feb;17(2):223-33. doi: 10.1017/S146114571300134X.

  PMID: 24393456 DERIVED

MeSH Terms

Conditions

Substance-Related Disorders

Interventions

Sugars; Varenicline

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

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

Study Officials

• Richard De La Garza, II, PhD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 20, 2012
• First Posted: April 5, 2012
• Study Start: January 1, 2011
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: June 13, 2013

Record last verified: 2013-06

Locations

US (1)