Publications

BACKGROUND & AIMS

Gluten ingestion leads to small intestinal mucosal injury in patients with celiac disease, necessitating strict life-long exclusion of dietary gluten. Despite adherence to a gluten-free diet, many patients remain symptomatic and still have small intestinal inflammation. In this case, nondietary therapies are needed. We investigated the ability of ALV003, a mixture of 2 recombinant gluten-specific proteases given orally, to protect patients with celiac disease from gluten-induced mucosal injury in a phase 2 trial.

METHODS

We established the optimal daily dose of gluten to be used in a 6-week challenge study. Then, in the intervention study, adults with biopsy-proven celiac disease were randomly assigned to groups given ALV003 (n = 20) or placebo (n = 21) together with the daily gluten challenge. Duodenal biopsies were collected at baseline and after gluten challenge. The ratio of villus height to crypt depth and densities of intraepithelial lymphocytes were the primary end points.

RESULTS

A daily dose of 2 g gluten was selected for the intervention study. Sixteen patients given ALV003 and 18 given placebo were eligible for efficacy evaluation. Biopsies from subjects in the placebo group showed evidence of mucosal injury after gluten challenge (mean villus height to crypt depth ratio changed from 2.8 before challenge to 2.0 afterward; P = .0007; density of CD3(+) intraepithelial lymphocytes changed from 61 to 91 cells/mm after challenge; P = .0003). However, no significant mucosal deterioration was observed in biopsies from the ALV003 group. Between groups, morphologic changes and CD3(+) intraepithelial lymphocyte counts differed significantly from baseline to week 6 (P = .0133 and P = .0123, respectively). There were no statistically significant differences in symptoms between groups.

CONCLUSIONS

Based on a phase 2 trial, the glutenase ALV003 appears to attenuate gluten-induced small intestinal mucosal injury in patients with celiac disease in the context of an everyday gluten-free diet containing daily up to 2 g gluten. Clinicaltrial.gov,

NUMBERS

NCT00959114 and NCT01255696.

BACKGROUND

Non-dependent alcohol and substance use patterns are prevalent among men who have sex with men (MSM), yet few effective interventions to reduce their substance use are available for these men. We evaluated whether an adapted brief counseling intervention aimed at reducing HIV risk behavior was associated with secondary benefits of reducing substance use among episodic substance-using MSM (SUMSM).

METHODS

326 episodic SUMSM were randomized to brief Personalized Cognitive Counseling (PCC) intervention with rapid HIV testing or to rapid HIV testing only control. Both arms followed over 6 months. Trends in substance use were examined using GEE Poisson models with robust standard errors by arm. Reductions in frequency of use were examined using ordered logistic regression.

RESULTS

In intent-to-treat analyses, compared to men who received rapid HIV testing only, we found men randomized to PCC with rapid HIV testing were more likely to report abstaining from alcohol consumption (RR=0.93; 95% CI=0.89-0.97), marijuana use (RR=0.84; 95% CI=0.73-0.98), and erectile dysfunction drug use (EDD; RR=0.51; 95% CI=0.33-0.79) over the 6-month follow-up. PCC was also significantly associated with reductions in frequency of alcohol intoxication (OR=0.58; 95% CI=0.36-0.90) over follow-up. Furthermore, we found PCC was associated with significant reductions in number of unprotected anal intercourse events while under the influence of methamphetamine (RR=0.26; 95% CI=0.08-0.84).

CONCLUSION

The addition of adapted PCC to rapid HIV testing may have benefits in increasing abstinence from certain classes of substances previously associated with HIV risk, including alcohol and EDD; and reducing alcohol intoxication frequency and high-risk sexual behaviors concurrent with methamphetamine use.