Neurotrophin-3 improves functional constipation.
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.
Parkman
Henry P
HP
Temple University Hospital, Philadelphia, Pennsylvania 19140, USA.
Rao
Satish S C
SS
Reynolds
James C
JC
Schiller
Lawrence R
LR
Wald
Arnold
A
Miner
Philip B
PB
Lembo
Anthony J
AJ
Gordon
James M
JM
Drossman
Douglas A
DA
Waltzman
Lynn
L
Stambler
Nancy
N
Cedarbaum
Jesse M
JM
D000293:Adolescent; D000328:Adult; D000368:Aged; D003106:Colon / Q000187:drug effects* / Q000503:physiopathology; D003248:Constipation / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005772:Gastrointestinal Transit / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007267:Injections; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000008:administration & dosage*; D020933:Neurotrophin 3 / Q000008:administration & dosage*; D016896:Treatment Outcome
D009414:Nerve Growth Factors; D020933:Neurotrophin 3