Neurotrophin-3 improves functional constipation

Neurotrophin-3 (NT-3) is a neurotrophic factor involved in the growth, development, and function of the nervous system. In preliminary studies, s.c. recombinant methionyl-human NT-3 enhanced transit throughout the GI tract and increased stool frequency in normal and constipated subjects. Our aim was to assess 1) the dose-related effects of NT-3 on bowel function, colon transit, and symptoms of chronic constipation, and 2) its safety.

This was a double-blind, randomized, placebo-controlled phase II study. A total of 107 patients with a diagnosis of functional constipation (Rome II criteria) were randomized to receive 4 wk of double blind, s.c. injections of either placebo, 3 mg, or 9 mg NT-3 once per week (qW) or three times per week (TTW); or 9 mg NT-3 TTW for 1 wk, then qW. The primary endpoint was the change in number of spontaneous, complete bowel movements per week. Colon transit was assessed before and at end of treatment.

Compared with placebo, patients who received 9 mg NT-3 TTW showed significant increases in frequency of spontaneous, complete bowel movements and total bowel movements, as well as dose-related softening of stool and improved ease of passage. The number of days per week without a bowel movement also decreased, colon transit improved, as did constipation-related symptoms. Weekly dosing was ineffective. Transient injection-site reactions, seen in one third of patients receiving NT-3 TTW, were the most frequent adverse event.

NT-3, administered TTW, increased stool frequency, enhanced colon transit, and improved symptoms of chronic constipation. NT-3 seems to be a novel, safe, and effective agent for the treatment of functional constipation.