Chronic constipation in diabetes mellitus is associated with colonic motor dysfunction and is managed with laxatives. Cholinesterase inhibitors increase colonic motility. The study evaluated the effects of a cholinesterase inhibitor (pyridostigmine vs. placebo) on gastrointestinal and colonic transit and bowel function in diabetic patients with constipation.
After a 9-day baseline period, patients with diabetes mellitus and chronic constipation without defecatory disorder will be randomized to oral placebo or pyridostigmine, starting with 60 mg three times a day, increasing by 60 mg every third day up to the maximum tolerated dose of 120 mg three times a day; this dose will be maintained for 7 days. Gastrointestinal and colonic transit (assessed by scintigraphy) and bowel function will be evaluated at baseline and the final 3 and 7 days of treatment, respectively.
Inclusion Criteria:
- Subjects with diabetes mellitus (Type I or type II), diagnosed by a physician.
- On medical treatment for diabetes (oral medication or injected insulin) for at least one year
- Symptomatic constipation at least 25% of the time in the past year (Rome II criteria for functional constipation)
- 18-70 years of age
- Colonoscopy negative for obstructive lesions, cancer, or inflammatory bowel disease (IBS) within the last 8 years if 50 years of age or older
- Able to provide written informed consent before participating in trial
- Able to communicate adequately with the Investigator and to comply with the requirements for the entire study
Exclusion Criteria:
- History of pelvic floor dysfunction (other functional GI disorders, eg IBS, non-ulcer dyspepsia are acceptable); Specifically, patients will be excluded if they have at least 2 of the following 3 criteria:
- History of digital evacuation of the rectum or pressure on the posterior aspect of the vagina or perineum to facilitate defecation
- Examination findings suggestive of puborectalis spasm or anismus, on assessment by an experienced gastroenterologist with expertise in this field; i.e. high anal sphincter tone at rest, failure of perineal descent by >1cm on straining, and tenderness or paradoxical contraction of the puborectalis on digital examination
- Requirement of > 200g to expel a rectal balloon during voluntary straining
- Abdominal surgery other than appendectomy, cholecystectomy, hysterectomy, tubal ligation, or inguinal hernia repair
- Suspected or known gastrointestinal or genitourinary obstruction
- Uncontrolled hypertension (defined as > 150/90 at rest)
- Known cardiac arrhythmia or ECG abnormalities, i.e. cardiac conduction disturbances (2nd or 3rd degree atrioventricular (AV) block, prolonged corrected QT interval (QTc)(> 460 msec) or bradycardia (< 45 beats/minute))
- Renal insufficiency with serum creatinine greater than 2 mg/dl based on a reading from the previous 6 months
- Asthma or chronic obstructive pulmonary disease requiring systemic steroids in the previous 3 years (inhaled steroids acceptable)
- Current use of narcotics, gut prokinetic drugs (eg metoclopramide, domperidone, tegaserod, senekot), anticholinergic medication (eg. Hyoscyamine, belladonna), antidiarrheals (Imodium, Lomotil), or laxatives other than fiber supplements, docusate, or glycerin suppositories. Patients on any of these restricted medications must cease use at least 48 hours before starting and for the duration of both study phases. No rescue laxatives will be permitted within 7 days of transit testing
- Patients who have taken any investigational medications within the past 30 days
- Known intolerance or allergy to eggs
- Pregnant or breast-feeding females
After completing a baseline/screening phase, participants will be put in one of 2 groups by chance (as in the flip of a coin). One group will receive 17 days of Pyridostigmine pills to take by mouth, and one group will receive 17 days of Placebo (a sugar pill with no active drug). Participants will not know which group they are in. They will be given the medication to take home with them after the first transit test.
The first 10 days of taking the medication is called the Drug Ramp period. During this time participants will slowly increase the number of study pills that are taken. They will start with one pill 3 times a day. Every 3rd day, participants will add another pill according to the schedule that is given to them.
Participants will be in the study for 24 days total. A period of up to 16 days is allowed between the Baseline and Medication Phase to fit this study into a participants schedule.
Last updated: 11/02/2012
NCT ID: NCT00276406
IRB Number:05-004037
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