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Neurotrophin-3 improves functional constipation.

Henry P Parkman·Satish S C Rao·James C Reynolds·Lawrence R Schiller·Arnold Wald·Philip B Miner·Anthony J Lembo·James M Gordon·Douglas A Drossman·Lynn Waltzman·Nancy Stambler·Jesse M Cedarbaum·Functional Constipation Study Investigators
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Abstract

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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AdolescentAdultAgedColonConstipationDose-Response Relationship, DrugDouble-Blind MethodFemaleGastrointestinal TransitHumansInjectionsMaleMiddle AgedNerve Growth FactorsNeurotrophin 3Treatment OutcomeClinical TrialClinical Trial, Phase IIJournal ArticleRandomized Controlled TrialResearch Support, Non-U.S. Gov't

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Henry P Parkman, Satish S C Rao, James C Reynolds, Lawrence R Schiller, Arnold Wald, Philip B Miner, Anthony J Lembo, James M Gordon, Douglas A Drossman, Lynn Waltzman, Nancy Stambler, Jesse M Cedarbaum, Functional Constipation Study Investigators. 2003. Neurotrophin-3 improves functional constipation.. https://doi.org/10.1111/j.1572-0241.2003.t01-1-07477.x

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