Cocaine vaccine for the treatment of cocaine dependence in methadone-maintained patients: a randomized, double-blind, placebo-controlled efficacy trial.

Abstract

CONTEXT:

Cocaine dependence, which affects 2.5 million Americans annually, has no US Food and Drug Administration-approved pharmacotherapy.

OBJECTIVES:

To evaluate the immunogenicity, safety, and efficacy of a novel cocaine vaccine to treat cocaine dependence.

DESIGN:

A 24-week, phase 2b, randomized, double-blind, placebo-controlled trial with efficacy assessed during weeks 8 to 20 and follow-up to week 24.

SETTING:

Cocaine- and opioid-dependent persons recruited from October 2003 to April 2005 from greater New Haven, Connecticut.

PARTICIPANTS:

One hundred fifteen methadone-maintained subjects (67% male, 87% white, aged 18-46 years) were randomized to vaccine or placebo, and 94 subjects (82%) completed the trial. Most smoked crack cocaine along with using marijuana (18%), alcohol (10%), and nonprescription opioids (44%).

INTERVENTION:

Over 12 weeks, 109 of 115 subjects received 5 vaccinations of placebo or succinylnorcocaine linked to recombinant cholera toxin B-subunit protein. Main Outcome Measure Semiquantitative urinary cocaine metabolite levels measured thrice weekly with a positive cutoff of 300 ng/mL.

RESULTS:

The 21 vaccinated subjects (38%) who attained serum IgG anticocaine antibody levels of 43 microg/mL or higher (ie, high IgG level) had significantly more cocaine-free urine samples than those with levels less than 43 microg/mL (ie, low IgG level) and the placebo-receiving subjects during weeks 9 to 16 (45% vs 35% cocaine-free urine samples, respectively). The proportion of subjects having a 50% reduction in cocaine use was significantly greater in the subjects with a high IgG level than in subjects with a low IgG level (53% of subjects vs 23% of subjects, respectively) (P = .048). The most common adverse effects were injection site induration and tenderness. There were no treatment-related serious adverse events, withdrawals, or deaths.

CONCLUSIONS:

Attaining high (>or=43 microg/mL) IgG anticocaine antibody levels was associated with significantly reduced cocaine use, but only 38% of the vaccinated subjects attained these IgG levels and they had only 2 months of adequate cocaine blockade. Thus, we need improved vaccines and boosters. Trial Registration clinicaltrials.gov Identifier: NCT00142857.

• Authors: Bridget A Martell, Frank M Orson, James Poling, Ellen Mitchell, Roger D Rossen, Tracie Gardner, Thomas R Kosten
• Journal: Archives of general psychiatry (Arch Gen Psychiatry) Vol. 66 Issue 10 Pg. 1116-23 (Oct 2009) ISSN: 1538-3636 [Electronic] United States
• PMID: 19805702 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Immunoglobulin G
• Methadone

Topics

• Adolescent
• Adult
• Cocaine-Related Disorders (blood, rehabilitation, therapy)
• Double-Blind Method
• Enzyme-Linked Immunosorbent Assay (statistics & numerical data)
• Female
• Follow-Up Studies
• Humans
• Immunoglobulin G (blood)
• Immunotherapy, Active (methods)
• Male
• Methadone (therapeutic use)
• Middle Aged
• Opioid-Related Disorders (rehabilitation, therapy)
• Substance Abuse Detection
• Treatment Outcome