Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00276406
Other study ID # 05-004037
Secondary ID UL1RR024150-01P0
Status Completed
Phase Phase 1/Phase 2
First received January 11, 2006
Last updated November 2, 2012
Start date May 2006
Est. completion date October 2010

Study information

Verified date November 2012
Source Mayo Clinic
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug AdministrationUnited States: Institutional Review Board
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 30
Est. completion date October 2010
Est. primary completion date October 2010
Accepts healthy volunteers No
Gender Both
Age group 18 Years to 70 Years
Eligibility 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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment


Intervention

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

Locations

Country Name City State
United States Mayo Clinic Rochester Minnesota

Sponsors (3)

Lead Sponsor Collaborator
Mayo Clinic National Center for Research Resources (NCRR), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & 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;6 — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary 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) No
Primary 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) No
Secondary Gastric Emptying Half-time (GE t1/2) The measure of time for 50 percent of a radio-labeled meal to empty from the stomach. Baseline period (9 days), Treatment period (7 days) No
Secondary Colonic Filling at 6 Hours The proportion of a radio-labeled meal in the colon at 6 hours (identifiable by radio-labelled tracer to capsule eaten with meal), measured by scintigraphy. This is an indirect measurement of small-bowel transit time. Baseline period (9 days), Treatment period (7 days) No
Secondary Colonic Geometric Center at 48 Hours (GC48) as 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 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. GC48 is the measurement taken at 48 hours after the radio-labeled meal. Baseline period (days 7-9 ), Treatment period (days 14-17) No
Secondary Stool Frequency Per Day During 9 days of the baseline period and during 17 days of the treatment period, subjects used a daily diary to record the number of times per day they had a bowel movement. Only the 7 days of highest treatment dose will be used for comparison purposes. Daily during baseline period (9 days), Treatment period (7 days) No
Secondary Stool Form/Consistency During 9 days of the baseline period and during 17 days of the treatment period, subjects used a daily diary to record a description of stool consistency according to the Bristol Stool Form Scale (ranging from 1 (hard lumps) to 7 (watery)). The Bristol Stool Scale is a medical aid designed to classify the form of human feces into seven categories or types. Types 1 and 2 indicate constipation with 3 and 4 being the "ideal stools" especially the latter, as they are the easiest to defecate, and 5-7 tending towards diarrhea. Daily during baseline period (9 days), Treatment period (7 days) No
Secondary Stool Ease of Passage During 9 days of the baseline period and during 17 days of the treatment period, subjects used a daily diary to record a description of stool ease of passage of stool, according to the Bristol Stool Form Scale (ranging from 1 (manual disimpaction) to 7 (incontinence)). Only the 7 days at highest treatment dose will be used for comparison purposes. Daily during baseline period (9 days), Treatment period (7 days) No
Secondary Sense of Completely Emptying Bowels During 9 days of the baseline period and during 17 days of the treatment period, subjects used a daily diary to record whether or not they felt they had completely emptied their bowels(1= Yes; 0= No). Only the 7 days of highest treatment dose will be used for comparison purposes. Daily during baseline period (9 days), Treatment period (7 days) No
Secondary Stool Frequency Per Week During 9 days of the baseline period and during 17 days of the treatment period, subjects used a daily diary to record the number of times per day they had a bowel movement. Complete spontaneous bowel movements per week are reported. Only the 7 days of highest treatment dose will be used for comparison purposes. Daily during baseline period (9 days), Treatment period (7 days) No
Secondary Heart Rate Before and After Treatment Heart rate is the number of beats per minute, as recording on an Electrocardiogram (ECG). Baseline period (9 days), Treatment period (7 days) Yes
Secondary QTc Interval Before and After Treatment The corrected QT interval (QTc) is a measurement of time (seconds) between the Q and T waves of an heart beat as recorded during an Electrocardiogram (ECG). Baseline period (9 days), Treatment period (7 days) Yes
See also
  Status Clinical Trial Phase
Completed NCT03743779 - Mastering Diabetes Pilot Study
Completed NCT03786978 - Pharmaceutical Care in the Reduction of Readmission Rates in Diabetes Melitus N/A
Completed NCT01804803 - DIgital Assisted MONitoring for DiabeteS - I N/A
Completed NCT05039970 - A Real-World Study of a Mobile Device-based Serious Health Game on Session Attendance in the National Diabetes Prevention Program N/A
Completed NCT04507867 - Effect of a NSS to Reduce Complications in Patients With Covid-19 and Comorbidities in Stage III N/A
Completed NCT04068272 - Safety of Bosentan in Type II Diabetic Patients Phase 1
Completed NCT03243383 - Readmission Prevention Pilot Trial in Diabetes Patients N/A
Completed NCT03730480 - User Performance of the CONTOUR NEXT and CONTOUR TV3 Blood Glucose Monitoring System (BGMS) N/A
Recruiting NCT02690467 - Efficacy, Safety and Acceptability of the New Pen Needle 34gx3,5mm. N/A
Completed NCT02229383 - Phase III Study to Evaluate Safety and Efficacy of Added Exenatide Versus Placebo to Titrated Basal Insulin Glargine in Inadequately Controlled Patients With Type II Diabetes Mellitus Phase 3
Completed NCT06181721 - Evaluating Glucose Control Using a Next Generation Automated Insulin Delivery Algorithm in Patients With Type 1 and Type 2 Diabetes N/A
Completed NCT05799976 - Text Message-Based Nudges Prior to Primary Care Visits to Increase Care Gap Closure N/A
Recruiting NCT04489043 - Exercise, Prediabetes and Diabetes After Renal Transplantation. N/A
Withdrawn NCT03319784 - Analysis for NSAID VS Corticosteroid Shoulder Injection in Diabetic Patients Phase 4
Completed NCT03542084 - Endocrinology Auto-Triggered e-Consults N/A
Completed NCT02229396 - Phase 3 28-Week Study With 24-Week and 52-week Extension Phases to Evaluate Efficacy and Safety of Exenatide Once Weekly and Dapagliflozin Versus Exenatide and Dapagliflozin Matching Placebo Phase 3
Recruiting NCT05544266 - Rare and Atypical Diabetes Network
Completed NCT01892319 - An International Non-interventional Cohort Study to Evaluate the Safety of Treatment With Insulin Detemir in Pregnant Women With Diabetes Mellitus. Diabetes Pregnancy Registry
Completed NCT05031000 - Blood Glucose Monitoring Systems: Discounter Versus Brand N/A
Recruiting NCT04039763 - RT-CGM in Young Adults at Risk of DKA N/A

External Links