Official Title: “Cocaine Withdrawal and Pharmacotherapy Response”

A total of 20 male and female opioid dependent cocaine users will participate in this study.

This study will be a 8 -week open label study examining the dose-dependent effects of carvedilol (up to 50mg/day) in methadone stabilized patients. The design will have two phases: 1) a four-week "treatment " phase; and 2) a 4 week " taper and detoxification or transfer" phase. Subjects will be cocaine users who are on stable doses of methadone (60 to 140mg/day). Carvedilol dose will be increased from 12.5mg/day to the target dose of 50mg/day as tolerated. At the end of the treatment-phase, subjects will undergo detoxification from methadone over a 2 to 4-week period based on an individual's needs, and they will concurrently be tapered off carvedilol.

Currently this study's recruitment stopped as of July 1, 2008 with 17 completers.

Study Type: Interventional

Study Design: Health Services Research, Randomized, Double Blind (Subject, Investigator), Placebo Control, Crossover Assignment

Study Primary Completion Date: September 2010

The adrenergic neurotransmission serves multiple functions including learning, emotional processing and stress response to psychological and physical challenges (Huether, 1996; Sved et al., 2001). Adrenergic transmission also mediates drug withdrawal states and stress-induced relapse to drug use (Aston-Jones et al., 2004; Stewart, 2000). Consistent with these preclinical findings, adrenergic blockers showed promise as a treatment of cocaine dependence (Kampman et al., 2001b; Kampman et al., 2006). These preliminary findings are significant because there are no proven pharmacotherapies for cocaine addiction although an estimated 2.3 million of Americans aged 12 or older are regular cocaine users (SAMHSA, 2004).

The societal cost of cocaine addiction is estimated to be $45 billion in the US, suggesting that development of even modestly effective cocaine pharmacotherapies will have great economic benefits. For example, availability of a medication decreasing cocaine use by 10 percent is estimated to have $745 million economic benefit in the US alone (Cartwright, 2000). Thus, developing effective treatments for cocaine addiction is an essential goal with significant benefits both for the society and the individual.

Intervention(s) in this Clinical Trial

• Drug: Carvedilol
  • Dosage is determined on an individual level due to patient weight and tolerance
• Drug: sugar pill
  • randomly given 25mg or 50mg of a sugar pill or the active comparator
• Drug: carvedilol
  • randomly assigned to 25mg or 50mg of Carvedilol or sugar pill

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: Sugar Pill
• Active Comparator: drug

Primary Measures

• To test the efficacy of an alpha- and beta -adrenergic blocker, carvedilol, in reducing cocaine use in methadone maintained cocaine users and to test whether the efficacy of carvedilol is moderated by cocaine withdrawal severity.
  • Time Frame: Four years
    Safety Issue?: No

Inclusion Criteria:

• Current opioid dependence as evidenced by documented prior treatment for opioid dependence or signs of opiate withdrawals, self -reported history of opioid dependence for a consecutive 12month period and a positive urine for opiates.
• Current cocaine use with self-reported use of cocaine > 1 time/week in at least on month preceding study entry, provision of a cocaine-positive urine and fulfilled
• DSM-IV criteria for cocaine dependence
• For women of childbearing age, a negative pregnancy test at screening with agreement to use adequate contraception to prevent pregnancy and monthly pregnancy tests.

Exclusion Criteria:

• · current diagnosis of other drug or alcohol dependence (other than opiates, cocaine or tobacco);
• serious medical illness including asthma, diabetes, bradycardia, or other arrhythmias and major cardiovascular, renal, endocrine, hepatic disorders;
• current serious psychiatric illness or history of psychosis, schizophrenia, bipolar type I disorder or significant current suicidal or homicidal thoughts;
• screening liver function tests (AST or ALT) greater than 3 times normal;
• known allergy or intolerance for carvedilol or methadone.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute on Drug Abuse (NIDA)

Overall Clinical Trial Officials and Contacts

Mehmet Sofuoglu, M.D., Ph.D. Principal Investigator Yale University  

Overall Contact: Stacy Minnix, Bsw 937-4805 stacy.minnix@yale.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00566969

Study ID Number: NIDA R01DA014537

ClinicalTrials.gov Identifier: NCT00566969

Health Authority: United States: Federal Government