Use of Pyridostigmine for Constipation in Diabetics
Use of Pyridostigmine for Constipation in Diabetics
Doctors at Mayo Clinic are doing this study to learn if pyridostigmine, a drug, affects the
 speed at which food travels through the stomach, intestines and colon, and if pyridostigmine
 improves constipation symptoms in patients with diabetes. Pyridostigmine has been approved by
 the Food and Drug Administration (FDA) for routine clinical use, however, its use as proposed
 in this study is considered investigational.
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