title: Vaccine for cocaine dependence: a randomized double-blind placebo-controlled efficacy trial.
abstract: OBJECTIVE
  We evaluated the immunogenicity, efficacy, and safety of succinylnorcocaine conjugated to cholera toxin B protein as a vaccine for cocaine dependence.
  
  
  METHODS
  This 6-site, 24 week Phase III randomized double-blind placebo-controlled trial assessed efficacy during weeks 8 to 16. We measured urine cocaine metabolites thrice weekly as the main outcome.
  
  
  RESULTS
  The 300 subjects (76% male, 72% African-American, mean age 46 years) had smoked cocaine on average for 13 days monthly at baseline. We hypothesized that retention might be better and positive urines lower for subjects with anti-cocaine IgG levels of ≥42 μg/mL (high IgG), which was attained by 67% of the 130 vaccine subjects receiving five vaccinations. Almost 3-times fewer high than low IgG subjects dropped out (7% vs 20%). Although for the full 16 weeks cocaine positive urine rates showed no significant difference between the three groups (placebo, high, low IgG), after week 8, more vaccinated than placebo subjects attained abstinence for at least two weeks of the trial (24% vs 18%), and the high IgG group had the most cocaine-free urines for the last 2 weeks of treatment (OR=3.02), but neither were significant. Injection site reactions of induration and tenderness differed between placebo and active vaccine, and the 29 serious adverse events did not lead to treatment related withdrawals, or deaths.
  
  
  CONCLUSIONS
  The vaccine was safe, but it only partially replicated the efficacy found in the previous study based on retention and attaining abstinence.
authors.affiliation: Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe, Bldg. 121, Rm 141, Houston, TX 77030, United States. Electronic address: Kosten@bcm.edu.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kosten
authors.affiliation: Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe, Bldg. 121, Rm 141, Houston, TX 77030, United States.
authors.forename: Coreen B
authors.initials: CB
authors.lastname: Domingo
authors.affiliation: Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe, Bldg. 121, Rm 141, Houston, TX 77030, United States.
authors.forename: Daryl
authors.initials: D
authors.lastname: Shorter
authors.affiliation: Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe, Bldg. 121, Rm 141, Houston, TX 77030, United States.
authors.forename: Frank
authors.initials: F
authors.lastname: Orson
authors.affiliation: University of Texas, Houston, TX 77030, United States.
authors.forename: Charles
authors.initials: C
authors.lastname: Green
authors.affiliation: University of Cincinnati, Cincinnati, OH, United States.
authors.forename: Eugene
authors.initials: E
authors.lastname: Somoza
authors.affiliation: University of Cincinnati, Cincinnati, OH, United States.
authors.forename: Rachelle
authors.initials: R
authors.lastname: Sekerka
authors.affiliation: Columbia University, New York, NY, United States.
authors.forename: Frances R
authors.initials: FR
authors.lastname: Levin
authors.affiliation: Columbia University, New York, NY, United States.
authors.forename: John J
authors.initials: JJ
authors.lastname: Mariani
authors.affiliation: Johns Hopkins University, Baltimore, MD, United States.
authors.forename: Maxine
authors.initials: M
authors.lastname: Stitzer
authors.affiliation: Johns Hopkins University, Baltimore, MD, United States.
authors.forename: D Andrew
authors.initials: DA
authors.lastname: Tompkins
authors.affiliation: NYU/VA NYHHS, New York, NY, United States.
authors.forename: John
authors.initials: J
authors.lastname: Rotrosen
authors.affiliation: NYU/VA NYHHS, New York, NY, United States.
authors.forename: Vatsal
authors.initials: V
authors.lastname: Thakkar
authors.affiliation: NYU/VA NYHHS, New York, NY, United States.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Smoak
authors.affiliation: University of Pennsylvania, Philadelphia, PA, United States.
authors.forename: Kyle
authors.initials: K
authors.lastname: Kampman
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000032:analysis; D003042:Cocaine / Q000276:immunology; D019970:Cocaine-Related Disorders / Q000276:immunology / Q000517:prevention & control*; D004311:Double-Blind Method; D005006:Ethnicity; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D012449:Safety; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods; D014612:Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000906:Antibodies; D014612:Vaccines; D003042:Cocaine
keywords: Clinical trial; Cocaine; Immunotherapy; Vaccine