A Study of the Relationship Between Disulfiram and Cocaine Self-administration.

NCT00729300 | Completed Phase 1 Results DMC

• 1 other identifier: H-23131
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

The problem of cocaine dependence remains a major medical, social, and legal concern. Several studies have suggested that disulfiram may be beneficial for the treatment of cocaine dependence. A common assumption has been that disulfiram treatment, by increasing DA availability, enhances the aversive aspects of stimulants. This study aims to measure plasma activity in those with the C/C DBH genotype, which is associated with higher DBH activity subsequently making the disulfiram treatment more effective, as well as determine the effects of treatment with disulfiram on cocaine self-administration using a human laboratory model of cocaine self-administration.

Conditions

Cocaine Addiction

Keywords

cocaine; disulfiram; antabuse; addiction; stimulant

Outcome Measures

Primary Outcomes (1)

• Cocaine Self-administration

  The reinforcing effects of cocaine were determined using a self-administration procedure in which subjects choose to take previously sampled doses of cocaine or cash of increasing monetary value. The mean number of cocaine choices across each drug condition (i.e., placebo and disulfiram) is reported.

  4 days

Study Arms (2)

1

PLACEBO COMPARATOR

Placebo

Drug: placebo

2

EXPERIMENTAL

disulfiram

Drug: disulfiram

Interventions

placebo DRUG

0mg daily

1

disulfiram DRUG

250mg daily

2

Eligibility Criteria

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

You may qualify if:

• \. Meet DSM IV criteria for cocaine dependence; 2. Have a self-reported history of using cocaine by the smoked or IV route. Participants must report at least weekly use for the past month and have a cocaine-positive urine test in the week of study entry; 3. Have vital signs after a 48 hours washout period as follows: resting pulse between 50 and 80 bpm, blood pressures between 105-130mm Hg systolic and 45-80mm Hg diastolic; 4. 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; 5. Have a baseline ECG that demonstrates normal sinus rhythm, normal conduction, and no clinically significant arrhythmias; and 6. Have a medical history and standard physical examination demonstrating no clinically significant contraindications for study participation, in the judgment of the admitting physician and the principal investigator.

You may not qualify if:

• \. Have any history or evidence suggestive of seizures or brain injury 2. Have any previous medically adverse reaction to cocaine, including loss of consciousness, chest pain, or epileptic seizure; 3. Have neurological or psychiatric disorders, such as:
• psychosis, bipolar illness or major depression as assessed by MINI (or SCID if necessary);
• 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 MINI and/or current suicidal ideation/plan as assessed by MINI; 4. Have evidence of clinically significant heart disease or hypertension, as determined by the PI; 5. Have a family history in first degree relatives of early cardiovascular morbidity or mortality, as determined by the PI; 6. Have evidence of untreated or unstable medical illness including: neuroendocrine, autoimmune, renal, hepatic, or active infectious disease; 7. Have HIV and are currently symptomatic, have a diagnosis of AIDS, or are receiving antiretroviral medication; 8. Have any history of asthma, chronic coughing and wheezing, or other respiratory illnesses; 9. Heavy current alcohol intake that is likely to lead to withdrawal symptoms, in the opinion of the PI; 10. Refuse to abstain from alcohol during the protocol and for at least one week after discharge.
• \. 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 the study.

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (1)

Baylor College of Medicine

Houston, Texas, 77056, United States

Location

Related Publications (1)

• Haile CN, De La Garza R 2nd, Mahoney JJ 3rd, Nielsen DA, Kosten TR, Newton TF. The impact of disulfiram treatment on the reinforcing effects of cocaine: a randomized clinical trial. PLoS One. 2012;7(11):e47702. doi: 10.1371/journal.pone.0047702. Epub 2012 Nov 8.

  PMID: 23144826 DERIVED

MeSH Terms

Conditions

Cocaine-Related Disorders; Behavior, Addictive

Interventions

Disulfiram

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Compulsive Behavior; Impulsive Behavior; Behavior

Intervention Hierarchy (Ancestors)

Ditiocarb; Thiocarbamates; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Disulfides; Sulfides; Sulfur Compounds

Limitations and Caveats

First, we focused on behavioral effects and did not obtain subjective measures (i.e., euphoria and craving). This could have contributed to our understanding of how disulfiram enhanced cocaine's reinforcing effects. Second, we administered cocaine by the IV route whereas a majority of our participants took cocaine by smoking, and this may have influenced certain outcomes. Finally, we treated participants for only a few days, whereas clinical trials last much longer.

Results Point of Contact

• Title: Christopher Verrico
• Organization: Baylor College of Medicine

verrico@bcm.edu

713-791-1313

Study Officials

• Thomas Newton, MD

  Baylor College of Medicine

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Psychiatry Research

Study Record Dates

• First Submitted: August 6, 2008
• First Posted: August 7, 2008
• Study Start: April 1, 2006
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: July 19, 2023
• Results First Posted: July 19, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)