Cocaine Withdrawal and Pharmacotherapy Response

Condition(s) targeted: To be Drug Free. Decrease the Amount of Cocaine Used While Participating in This Study.

Intervention: sugar pill (Drug); carvedilol (Drug); Methadone (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: National Institute on Drug Abuse (NIDA)

Official(s) and/or principal investigator(s):
Mehmet Sofuoglu, M.D., Ph.D., Principal Investigator, Affiliation: Yale University

Overall contact:
Stacy Minnix, Bsw, Phone: 937-4805, Email: stacy.minnix@yale.edu

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.

Official title: Cocaine Withdrawal and Pharmacotherapy Response

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

Primary outcome: 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.

Detailed description: 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.

This study is active and ongoing. Recruitment is ongoing. 9.9. 09

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

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.

Stacy Minnix, Bsw, Phone: 937-4805, Email: stacy.minnix@yale.edu

Veterans Hospital, West Haven, Connecticut 06516, United States; Recruiting
Mehmet Sofuoglu, M.D., Ph.D., Phone: 203-937-4809, Email: mehmet.sofuoglu@yale.edu
Mehmet Sofuoglu, M.D., Ph.D., Principal Investigator

Starting date: September 2007
Ending date: September 2011
Last updated: September 9, 2009