Cocaine vaccine for the treatment of cocaine dependence in methadone-maintained patients: a randomized, double-blind, placebo-controlled efficacy trial.
BACKGROUND
Cocaine dependence, which affects 2.5 million Americans annually, has no US Food and Drug Administration-approved pharmacotherapy.


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


METHODS
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.


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


METHODS
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%).


METHODS
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.
Martell
Bridget A
BA
Department of Medicine, Yale University School of Medicine, New Haven, CT, USA.
Orson
Frank M
FM
Poling
James
J
Mitchell
Ellen
E
Rossen
Roger D
RD
Gardner
Tracie
T
Kosten
Thomas R
TR
D000293:Adolescent; D000328:Adult; D019970:Cocaine-Related Disorders / Q000097:blood / Q000534:rehabilitation / Q000628:therapy*; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay / Q000706:statistics & numerical data; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016233:Immunotherapy, Active / Q000379:methods*; D008297:Male; D008691:Methadone / Q000627:therapeutic use*; D008875:Middle Aged; D009293:Opioid-Related Disorders / Q000534:rehabilitation / Q000628:therapy; D015813:Substance Abuse Detection; D016896:Treatment Outcome
D007074:Immunoglobulin G; D008691:Methadone