Use of Pyridostigmine for Constipation in Diabetics

NCT00276406 | Completed Phase 1 Results DMC

• 3 other identifiers: 05-004037UL1RR024150-01P01DK068055
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Constipation; Diabetes Mellitus; Colonic Transit; Gastric Emptying

Outcome Measures

Primary Outcomes (2)

• Colonic Geometric Center at 24 Hours (GC24) Measured by Scintigraphy

  The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images of the abdomen are taken hourly for the first 6 hours after the radio-labeled meal, then at 8, 24 and 48 hours. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit, a GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool. GC24 is the measurement taken at 24 hours after the radio-labeled meal.

  Baseline period (days 7-9 ), Treatment period (days 14-17)

• Ascending Colon Emptying Half-time (AC t1/2) Measured in Hours

  Calculated by linear interpolation of values on the AC emptying curve.

  Baseline period (days 7-9 ), Treatment period (days 14-17)

Secondary Outcomes (10)

• Gastric Emptying Half-time (GE t1/2)

  Baseline period (9 days), Treatment period (7 days)

• Colonic Filling at 6 Hours

  Baseline period (9 days), Treatment period (7 days)

• Colonic Geometric Center at 48 Hours (GC48) as Measured by Scintigraphy

  Baseline period (days 7-9 ), Treatment period (days 14-17)

• Stool Frequency Per Day

  Daily during baseline period (9 days), Treatment period (7 days)

• Stool Form/Consistency

  Daily during baseline period (9 days), Treatment period (7 days)

Study Arms (2)

Pyridostigmine

EXPERIMENTAL

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.

Drug: Pyridostigmine

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Pyridostigmine DRUG

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

Also known as: Mestinon

Pyridostigmine

Placebo 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.

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• National Center for Research Resources (NCRR): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• 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.

  PMID: 22677718 RESULT

MeSH Terms

Conditions

Constipation; Diabetes Mellitus

Interventions

Pyridostigmine Bromide

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Pyridinium Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Adil E. Bharucha, MD
• Organization: Mayo Clinic

bharucha.adil@mayo.edu

507-284-6439

Study Officials

• Adil E. Bharucha, MBBS, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Professor of Medicine

Study Record Dates

• First Submitted: January 11, 2006
• First Posted: January 13, 2006
• Study Start: May 1, 2006
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: November 30, 2012
• Results First Posted: November 30, 2012

Record last verified: 2012-11

Locations

US (1)