Vaccine for cocaine dependence: a randomized double-blind placebo-controlled efficacy trial
Kosten, Thomas R; Domingo, Coreen B; Shorter, Daryl; Orson, Frank; Green, Charles; Somoza, Eugene; Sekerka, Rachelle; Levin, Frances R; Mariani, John J; Stitzer, Maxine; Tompkins, D Andrew; Rotrosen, John; Thakkar, Vatsal; Smoak, Benjamin; Kampman, Kyle
AIMS: 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 mug/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.
Effects of gum chewing on pharyngeal and esophageal pH
Smoak, B R; Koufman, J A
We investigated the effects of gum chewing on pharyngeal and esophageal pH levels in patients with laryngopharyngeal reflux (LPR) who were undergoing reflux testing. Forty consecutive, unselected, adult patients who were undergoing ambulatory double-probe (simultaneous pharyngeal and esophageal) pH monitoring for diagnosis of LPR were asked to chew 2 sticks of gum 4 times during their pH studies. Twenty subjects chewed regular sugarless gum, and 20 subjects chewed a sugarless gum containing bicarbonate. The subjects recorded the beginning and end of each gum-chewing period. The mean pH values for the gum-chewing intervals and for comparable pre-gum-chewing intervals were analyzed statistically for both the pharyngeal and esophageal probe data. The regular gum group and the bicarbonate gum group were analyzed separately. In addition, the gum-chewing pH data were compared to controls, ie, normal postcibal buffering effects. The data show that gum chewing consistently increases esophageal and pharyngeal pH, and that bicarbonate gum causes greater increases than regular gum. For patients with LPR, gum chewing appears to be a useful adjunctive antireflux therapy