OBJECTIVES: In this study, we evaluated the safety and efficacy of a personalized mode of treatment for Crohn's disease (CD) by oral administration of Alequel an extract of autologous colonic proteins. METHODS: Thirty-one patients with moderate to severe CD were enrolled in a 27-wk randomized, double-blind, placebo-controlled trial. Patients were randomized to receive either a placebo or the study drug prepared from autologous colonic extract. RESULTS: Oral administration of autologous colonic proteins resulted in clinical remission (58% vs 29%; 46.6% vs 26.6%, using an intention to treat analysis, p= NS), clinical response (67% vs 43%; 53.3% vs 40%, using an intention to treat analysis, p= NS) and improved quality of life (Inflammatory Bowel Disease Questionnaire score improvement 43%vs 12%) in the drug study group, compared to placebo group. No treatment-related adverse events were noted. Only in the study-drug-treated cohort who achieved clinical remission (DR), there was a decreased number of subject-specific, antigen-directed, IFNgamma spot-forming colonies. DR subjects had a lower initial C-reactive protein level than DNOR or placebo subjects, an increased percentage of peripheral blood nature killer T cells, and an increased CD4+/CD8+ T-cell ratio throughout the period of drug administration. CONCLUSIONS: Oral administration of Alequel is a safe method for treatment of patients with moderate to severe CD, and its efficacy needs to be proven. Several markers may be applicable as surrogate markers for the clinical effect.