Effectiveness of N-Acetylcysteine (NAC) in Treating Cocaine Dependent Individuals - 1 (NAC)

• ClinicalTrials.gov Identifier: NCT00218491
• Recruitment Status: Completed
• First Posted: September 22, 2005
• Results First Posted: January 15, 2019
• Last Update Posted: January 15, 2019
• Sponsor: Medical University of South Carolina
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): Robert Malcolm, Medical University of South Carolina

Study Description

Brief Summary:

Currently, no effective drug treatment exists for cocaine dependence. Glutamate levels are disrupted with long-term cocaine use. N-acetyl cysteine (NAC) is a drug that is metabolized by the body to form cysteine, an active compound that normalizes glutamate levels. The purpose of this study is to determine the safety and effectiveness of NAC in treating cocaine dependent individuals.

Condition or disease	Intervention/treatment	Phase
Cocaine Dependence	Drug: N-Acetylcysteine; Drug: Matching Placebo	Phase 2

Detailed Description:

Currently, no effective pharmacological treatment exists for cocaine dependence. Long-term use of cocaine disrupts normal glutamate levels. If addicts stop using cocaine, glutamate levels drop, which encourages addicts to continue seeking the drug. NAC is a drug that increases intracellular cysteine levels, which in turn leads to normalization of glutamate levels. Currently, NAC is used for the treatment of cystic fibrosis, heart disease, and acetaminophen overdose. Since NAC has the capability of restoring normal glutamate levels, it holds potential as a treatment for cocaine dependence. The purpose of this study is to determine the safety and effectiveness of NAC in treating cocaine dependent individuals. In addition, this study will evaluate cocaine craving and withdrawal symptoms in individuals taking NAC.

Participants in this double-blind, placebo-controlled trial will be randomly assigned to receive either NAC or placebo. All participants will undergo an initial evaluation, which will include a physical examination, an electrocardiogram, blood samples, urine tests, and cue reactivity measures. Participants in the NAC group will receive either 600 mg or 1200 mg of NAC, two times each day for 8 weeks. In addition, all participants will receive cognitive behavioral therapy throughout the study on a weekly basis. Cocaine use will be confirmed by a urine drug screen test, three times each week. Participants will be assessed on a number of biomedical and psychosocial variables known to influence cocaine treatment outcomes. After Week 2, participants will repeat the cue reactivity procedures, which will include measuring a participant's craving response when exposed to conditioned reminders of prior cocaine use.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 111 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Controlled Trial of N-Acetylcysteine (NAC) for Cocaine Dependence
• Study Start Date: November 2005
• Actual Primary Completion Date: May 2010
• Actual Study Completion Date: May 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1200mg N-Acetylcysteine; 1200mg N-Acetylcysteine	Drug: N-Acetylcysteine; 1200mg N-Acetylcysteine
Experimental: 2400mg N-Acetylcysteine; 2400mg N-Acetylcysteine	Drug: N-Acetylcysteine; 2400mg N-Acetylcysteine
Placebo Comparator: Matching Placebo; Matching Placebo	Drug: Matching Placebo; Matching Placebo

Outcome Measures

Primary Outcome Measures :

1. Number of Participants That Achieved Study Compliance [ Time Frame: 8 weeks ]
   Drug and placebo compliance were measured by urine riboflavin levels. Study compliance was defined as 80% or greater weekly urine riboflavin levels equal to or greater than 1500 ng/ml

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Meets DSM-IV criteria for cocaine dependence, as determined by a mini-SCID interview
• Currently dependent on cocaine
• Seeking treatment for cocaine abuse at the time of study entry
• Currently uses cocaine by smoking, nasal, or intravenous route of administration.
• Stable physical and mental health, as judged by an interview and physical examination
• If female, demonstrates a negative pregnancy test and agrees to use an adequate method of contraception for the duration of the study
• Lives within a 50 mile radius of the research program center and has reliable transportation

Exclusion Criteria:

• Meets DSM-IV criteria for dependence on any psychoactive substance other than cocaine, alcohol, nicotine, or marijuana
• Physiological dependence on alcohol, which requires medical detoxification
• History of significant liver, kidney, endocrine, cardiac (e.g., arrhythmia requiring medication, angina pectoris, myocardial infarction), stroke, seizure, neurological, non-drug-related psychiatric, gastrointestinal, pulmonary, hematologic, or metabolic disorders (e.g., homocystinuria)
• History of an adverse reaction to cocaine, including loss of consciousness, chest pain, psychosis, or seizure
• History of adverse reaction or hypersensitivity to N-acetyl cystine (NAC), or a similar drug
• Significant active medical or psychiatric illness that might inhibit the ability to complete the study
• Active high blood pressure, defined as a mean of three sitting blood pressure readings of 145/95 or higher within a 10-day period
• History of or current asthma
• Occasional or daily use of albuterol or other beta-agonist inhalers
• Use of carbamazepine, phenytoin, nitrous oxide, methotrexate, 6 azauridine triacetate, or nitroglycerin within the 2 weeks prior to study entry
• Use of very large doses of folate, cyanocobalamine (vitamin B12), or pyridoxine (vitamin B6) as prescribed by a health care professional; individuals taking very large doses of these vitamins on a self-initiated basis may enter the study if they are willing to stop use 14 days prior to study entry and to use a standard generic multiple vitamin instead
• Pregnant or breastfeeding
• Required by the court to obtain treatment for cocaine dependence
• Not seeking treatment for cocaine dependence
• Anticipating elective surgery or hospitalization within 20 weeks of study entry
• Failure to have a consistent residence for the 4 weeks prior to study entry
• History of childhood or adult seizures
• Participated in cocaine treatment (clinical or research) within 30 days of study entry

Contacts and Locations

Locations

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29425

Sponsors and Collaborators

Medical University of South Carolina

National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Robert Malcolm, M.D.; Medical University of South Carolina

More Information

• Responsible Party: Robert Malcolm, Professor of Psychiatry, Family Medicine & Pediatrics, Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT00218491
• Other Study ID Numbers: NIDA-19903-1; R01DA019903 ( U.S. NIH Grant/Contract ); R01-19903-1; DPMC
• First Posted: September 22, 2005
• Results First Posted: January 15, 2019
• Last Update Posted: January 15, 2019
• Last Verified: December 2018

Keywords provided by Robert Malcolm, Medical University of South Carolina:

Cocaine Dependence

Additional relevant MeSH terms:

Cocaine-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Acetylcysteine; N-monoacetylcystine; Antiviral Agents; Anti-Infective Agents; Expectorants; Respiratory System Agents; Free Radical Scavengers; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Antidotes