NAC as a Potential Treatment for Methamphetamine Dependence

NCT01063205 | Completed Phase 1 DMC

• 3 other identifiers: H-24927DPMCR21DA024756
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the effects of treatment with NAC, compared to treatment with placebo, on cue- and methamphetamine (MA)-induced craving and MA subjective effects in non-treatment-seeking MA-dependent human volunteers. We also aim to determine the effects of treatment with NAC, compared to treatment with placebo, on the reinforcing effects of MA by measuring MA self-administration in non-treatment-seeking MA-dependent human volunteers.

Conditions

Methamphetamine Abuse; Methamphetamine Dependence; Substance Abuse

Keywords

Methamphetamine; NAC; N-acetylcysteine

Outcome Measures

Primary Outcomes (1)

• The effects of treatment with NAC (placebo, 1800 and 3600 mg daily), compared to treatment with placebo, on cue- and MA-induced craving and subjective effects in MA-dependent human volunteers.

  On days 3-5, participants will take part in active cues and neutral cues. On days 4 and 5, they will make choices to receive MA/placebo in a self-administration paradigm. Participants will also rate craving, desire, and would take MA if available on a 0-100 mm visual analogue scale.

Secondary Outcomes (1)

• The effects of treatment with NAC (placebo, 1800 and 3600 mg daily), compared to treatment with placebo, on the reinforcing effects of MA by measuring MA self-administration in MA-dependent human volunteers.

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

N-Acetylcysteine (NAC) 1800 mg

ACTIVE COMPARATOR

Drug: N-acetylcysteine

N-Acetylcysteine (NAC) 3600 mg

ACTIVE COMPARATOR

Drug: N-acetylcysteine

Interventions

Placebo DRUG

Placebo administration will be started on day 2 and stopped on day 5. Methylsulonylmethane (MSM) will serve as a placebo for MA.

Also known as: Methylsulonylmethane (MSM)

Placebo

N-acetylcysteine DRUG

Study medication (NAC 1800 mg) will be started on day 2 and stopped on day 5.

Also known as: NAC

N-Acetylcysteine (NAC) 1800 mg

Eligibility Criteria

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

You may qualify if:

• Be English-speaking non-treatment-seeking volunteers.
• Be between 18-55 years of age.
• Meet DSM-IV TR criteria for MA dependence.
• Have a self-reported history of using MA by the smoked route.
• Have vital signs as follows: resting pulse between 50 and 90 bpm, blood pressures between 85-150mm Hg systolic and 45-90mm Hg diastolic.
• Have a breathalyzer test indicating an undetectable blood alcohol level upon 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 ECG that demonstrates normal sinus rhythm, normal conduction, 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 and the principal investigator. Adult ADHD is allowable, as long as symptoms do not interfere with participation.

You may not qualify if:

• Have any previous medically adverse reaction to MA, including loss of consciousness, chest pain, or epileptic seizure.
• Have neurological or psychiatric disorders, such as: a. episode of major depression within the past 2 years as assessed by MINI; b. lifetime history of schizophrenia, other psychotic illness, or bipolar illness as assessed by MINI; c. current organic brain disease or dementia assessed by clinical interview; d. history of or any current psychiatric disorder which would require ongoing treatment or which would make study compliance difficult; e. history of suicide attempts within the past year and/or current suicidal ideation/plan. f. history of psychosis occurring in the absence of current MA use.
• Meet DSM-IV criteria for abuse or dependence on alcohol or other drugs, except for nicotine.
• Meet DSM-IV criteria for dependence on marijuana.
• Have evidence of clinically significant heart disease or hypertension, 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.
• Currently use alpha or beta agonists, theophylline, or other sympathomimetics.
• Have any other illness, condition, or use of medications, which in the opinion of the P.I. and/or the admitting physician would preclude safe and/or successful completion of the study.
• Have sulfur allergy.
• Criteria for Discontinuation Following Initiation:
• Rationale for Subject Selection Criteria:
• Participants are required to have used MA by the intravenous route in order to avoid exposing participants to new routes of administration. Participants with asthma or who take medications for asthma are excluded due to potential adverse interactions between treatment medications and MA. Participants who use alcohol heavily are excluded due to the potential of withdrawal symptoms in the hospital. Participants with active HIV disease are excluded to avoid potentially exacerbating their underlying illness.

Sponsors & Collaborators

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

Study Sites (1)

Michael E. DeBakey VA Medical Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Substance-Related Disorders

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Thomas Newton, MD

  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: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 3, 2010
• First Posted: February 5, 2010
• Study Start: March 1, 2010
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: July 27, 2012

Record last verified: 2012-07

Locations

US (1)