title: Niccine®, a nicotine vaccine, for relapse prevention: a phase II, randomized, placebo-controlled, multicenter clinical trial.
abstract: BACKGROUND
  A nicotine vaccine could prevent relapse to smoking by hindering blood nicotine from reaching the brain. Niccine® is a nicotine hapten tetanus-toxoid conjugate vaccine. The present study evaluated the clinical efficacy of Niccine for tobacco smoking relapse prevention.
  
  
  METHODS
  Cigarette smokers (n = 355) aged 25-50 years were enrolled in a randomized, double-blind, parallel group 1-year trial encompassing 16 visits and 16 telephone calls. Niccine 40 μg or placebo was administered on Days 0, 28, 56, 90, 150, and 210. Between Days 56-98, subjects were treated with varenicline to aid cessation, targeted for Day 70. Only individuals abstinent between Days 90-98 (n = 265) were allowed to continue to 1 year (n = 219). Relapse to smoking was defined as >5 cigarettes within 7 days or since the last contact, or smoking on >5 occasions within 7 days or since the last contact.
  
  
  RESULTS
  At 1 year, nonrelapse was 43.3% in the Niccine versus 51.1% in the placebo groups (difference = -7.9%; 95% CI = -20.6% to 4.9%). There was no benefit of Niccine on smoking status at 6 or 9 months, exhaled carbon monoxide levels, time to relapse, abstinence, withdrawal symptoms, or smoking reinforcement. Nicotine antibody levels increased (mean = 1.34 μg/ml; SD = 2.84 μg/ml) in the Niccine group, but were not related to relapse. Adverse events except hypersensitivity and compensatory smoking did not differ between groups.
  
  
  CONCLUSIONS
  This nicotine vaccine appeared well tolerated but did not influence trajectories of relapse possibly because of insufficient antibody levels or lack of efficacy of the vaccine concept for relapse prevention.
authors.affiliation: Department of Preventive Cardiology, Oslo University Hospital Ullevål, Norway. stonstad@llu.edu
authors.forename: Serena
authors.initials: S
authors.lastname: Tonstad
authors.forename: Eli
authors.initials: E
authors.lastname: Heggen
authors.forename: Hans
authors.initials: H
authors.lastname: Giljam
authors.forename: Per-Åke
authors.initials: PÅ
authors.lastname: Lagerbäck
authors.forename: Philip
authors.initials: P
authors.lastname: Tønnesen
authors.forename: Lena Degling
authors.initials: LD
authors.lastname: Wikingsson
authors.forename: Nina
authors.initials: N
authors.lastname: Lindblom
authors.forename: Sabina
authors.initials: S
authors.lastname: de Villiers
authors.forename: Torgny H
authors.initials: TH
authors.lastname: Svensson
authors.forename: Karl-Olov
authors.initials: KO
authors.lastname: Fagerström
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000276:immunology*; D016540:Smoking Cessation / Q000379:methods*; D014612:Vaccines / Q000627:therapeutic use*
chemical_list: D014612:Vaccines; D009538:Nicotine