A randomized, controlled exploratory study of clonidine in diarrhea-predominant irritable bowel syndrome.
OBJECTIVE
The aim of this study was to evaluate the efficacy and tolerability of the alpha-2 adrenoreceptor agonist, clonidine, in patients with diarrhea-predominant irritable bowel syndrome (D-IBS) in a double-blind, randomized, parallel-group, placebo-controlled trial.


METHODS
A 2-week run-in evaluated baseline symptoms. Patients received 0.05, 0.1, or 0.2 mg clonidine or placebo twice a day for 4 weeks. We evaluated satisfactory relief of IBS by weekly question and stool parameters with a daily diary. Satisfactory relief and overall bowel function were primary end points. Secondary end points were stool frequency, consistency, and ease of passage; gut transit; and fasting and postprandial gastric volumes. Analysis followed intention-to-treat principles.


RESULTS
Forty-four D-IBS patients participated; there were 4 treatment-related dropouts: 2/2 in the 0.2-mg and 2/12 in the 0.05-mg clonidine groups. Proportion with satisfactory relief of IBS was 0.46, 0.42, and 0.67 with placebo, 0.05 mg, and 0.1 mg clonidine, respectively. Relief was sustained through 4 weeks of treatment, and bowel dysfunction (firmer stools and easier stool passage [P < 0.05]) was reduced with clonidine, 0.1 mg twice a day. Clonidine did not significantly alter gastrointestinal transit or gastric volumes. Drowsiness, dizziness, and dry mouth were the most common adverse events with the 0.1-mg dose; severity of adverse effects subsided after the first week of treatment. A trial to replicate 20% or more responders with clonidine will require 95 patients per treatment arm.


CONCLUSIONS
Clonidine, 0.1 mg twice a day for 4 weeks, relieves bowel dysfunction and appears promising for relief of D-IBS; these effects are unassociated with significant alterations in transit.
Camilleri
Michael
M
Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Gastroenterology Research Unit, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA. camilleri.michael@mayo.edu
Kim
Doe-Young
DY
McKinzie
Sanna
S
Kim
H Jae
HJ
Thomforde
George M
GM
Burton
Duane D
DD
Low
Phillip A
PA
Zinsmeister
Alan R
AR
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003000:Clonidine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003672:Defecation; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005772:Gastrointestinal Transit; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000188:drug therapy*; D008365:Manometry; D010865:Pilot Projects; D019518:Postprandial Period; D015899:Tomography, Emission-Computed, Single-Photon
D000316:Adrenergic alpha-Agonists; D003000:Clonidine