Use of Pyridostigmine for Constipation in Diabetics

NCT ID: NCT00276406

Last Updated: 2012-11-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31
• Study Completion Date: 2010-10-31

Brief Summary

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.

Detailed Description

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.

Conditions

Constipation; Diabetes Mellitus; Colonic Transit; Gastric Emptying

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Pyridostigmine

Oral pyridostigmine, starting with 60 mg capsules three times per day (TID), increasing by 60 mg every third day (i.e., over 10 days) up to the maximum tolerated dose or 120 mg TID (a total of 360 mg per day). This dose was maintained for 7 days.

Group Type: EXPERIMENTAL

Pyridostigmine

Intervention Type: DRUG

Pyridostigmine will be started at (60mg) tid, increased over 10 days to 120 mg tid, and maintained at that dose for 7 days.

Placebo

Placebo (sham) capsules, matching the appearance of the active drug comparator and taken TID.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

If subject is randomized to placebo, placebo pills will be started at (60mg) tid, increased over 10 days to 120 mg tid, and maintained at that dose for 7 days.

Interventions

Pyridostigmine

Pyridostigmine will be started at (60mg) tid, increased over 10 days to 120 mg tid, and maintained at that dose for 7 days.

Intervention Type: DRUG

Placebo

If subject is randomized to placebo, placebo pills will be started at (60mg) tid, increased over 10 days to 120 mg tid, and maintained at that dose for 7 days.

Intervention Type: DRUG

Other Intervention Names

Mestinon

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

National Center for Research Resources (NCRR)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Adil Bharucha

MD, Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Adil E. Bharucha, MBBS, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

References

Bharucha AE, Low P, Camilleri M, Veil E, Burton D, Kudva Y, Shah P, Gehrking T, Zinsmeister AR. A randomised controlled study of the effect of cholinesterase inhibition on colon function in patients with diabetes mellitus and constipation. Gut. 2013 May;62(5):708-15. doi: 10.1136/gutjnl-2012-302483. Epub 2012 Jun 7.

Reference Type: RESULT

PMID: 22677718 (View on PubMed)

Other Identifiers

UL1RR024150-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P01DK068055

Identifier Type: NIH

Identifier Source: secondary_id

View Link

05-004037

Identifier Type: -

Identifier Source: org_study_id