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NAC as a Potential Treatment for Methamphetamine Dependence

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Thomas Newton, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT01063205
First received: February 3, 2010
Last updated: July 25, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Methamphetamine Abuse
Methamphetamine Dependence
Substance Abuse
Drug: Placebo
Drug: N-acetylcysteine
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Official Title: N-AcetylCysteine as a Potential Treatment of Methamphetamine Dependence

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • 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. [ Designated as safety issue: No ]
    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 Outcome Measures:
  • 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. [ Designated as safety issue: No ]
    On days 4 and 5, participants will make choices to receive MA/placebo in a self-administration paradigm. Any alterations in the reinforcing effects of MA associated with NAC treatment will be evident as changes in the number of choices made for MA.


Enrollment: 10
Study Start Date: March 2010
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
Placebo administration will be started on day 2 and stopped on day 5. Methylsulonylmethane (MSM) will serve as a placebo for MA.
Other Name: Methylsulonylmethane (MSM)
Active Comparator: N-Acetylcysteine (NAC) 1800 mg Drug: N-acetylcysteine
Study medication (NAC 1800 mg) will be started on day 2 and stopped on day 5.
Other Name: NAC
Active Comparator: N-Acetylcysteine (NAC) 3600 mg Drug: N-acetylcysteine
Study medication (NAC 3600 mg) will be started on day 2 and stopped on day 5.
Other Name: NAC

Detailed Description:

N-acetyl-l-cysteine (NAC) treatment is associated with reduced susceptibility to reinstatement of cocaine seeking behavior in rats (Baker et al 2002) and with reduced cue-induced craving in cocaine-dependent human volunteers (LaRowe et al 2006). We propose these aims to evaluate the potential of NAC as a treatment for methamphetamine (MA) dependence: Specific Aim 1: To determine the effects of treatment with NAC(placebo, 1800 and 3600mg daily), compared to treatment with placebo, on cue- and MA-induced craving and MA subjective effects in non-treatment-seeking MA-dependent human volunteers. We hypothesize that treatment with NAC will reduce craving for MA reported following exposure to MA cues and will reduce craving and MA subjective effects reported following non-contingent administration of MA (0mg,9mg, and 30 mg, IV). Specific Aim 2: To determine the effects of treatment with NAC (placebo, 1800 and 3600mg daily), compared to treatment with placebo, on the reinforcing effects of MA by measuring MA self-administration in non-treatment-seeking MA-dependent human volunteers. We hypothesize that treatment with NAC will reduce the number of choices made for MA during choice sessions.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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:

Participants will be discharged if they have a positive urine toxicology or breath test indicating illicit use of drugs while on the Research Commons, if they do not comply with study procedures, or if they do not tolerate MA. MA will not be administered if participants do not continue to meet inclusion criteria listed above or if the study physician believes there may be any reason to withhold MA.

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01063205

Locations
United States, Texas
Michael E. DeBakey VA Medical Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
Investigators
Principal Investigator: Thomas Newton, MD Baylor College of Medicine
  More Information

No publications provided

Responsible Party: Thomas Newton, Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT01063205     History of Changes
Other Study ID Numbers: H-24927, DPMC, R21DA024756
Study First Received: February 3, 2010
Last Updated: July 25, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Baylor College of Medicine:
Methamphetamine
NAC
N-acetylcysteine

Additional relevant MeSH terms:
Acetylcysteine
Methamphetamine
N-monoacetylcystine
Adrenergic Agents
Adrenergic Uptake Inhibitors
Anti-Infective Agents
Antidotes
Antioxidants
Antiviral Agents
Autonomic Agents
Central Nervous System Agents
Central Nervous System Stimulants
Dopamine Agents
Dopamine Uptake Inhibitors
Expectorants
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Respiratory System Agents
Sympathomimetics
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014