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Phase 2 N=30 Randomized Triple-blind Treatment

Use of Pyridostigmine for Constipation in Diabetics

Constipation · Diabetes Mellitus · Colonic Transit · Gastric Emptying

Enrolled (actual)
30
Serious AEs
0.0%
Results posted
Nov 2012
Primary outcome: Primary: Colonic Geometric Center at 24 Hours (GC24) Measured by Scintigraphy — 1.96; 1.98; 2.45; 1.84 units on a scale — p=<0.01

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
Pyridostigmine (Drug); Placebo (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Mayo Clinic
Primary completion
Oct 2010

Outcome Measures

OutcomeResultp-value
PRIMARY
Colonic Geometric Center at 24 Hours (GC24) Measured by Scintigraphy
1.96; 1.98; 2.45; 1.84 <0.01 sig
PRIMARY
Ascending Colon Emptying Half-time (AC t1/2) Measured in Hours
16.73; 20.59; 10.44; 18.77
SECONDARY
Gastric Emptying Half-time (GE t1/2)
142; 141; 122; 121
SECONDARY
Colonic Filling at 6 Hours
37; 41; 53; 48
SECONDARY
Colonic Geometric Center at 48 Hours (GC48) as Measured by Scintigraphy
2.92; 2.97; 3.59; 3.26 0.096
SECONDARY
Stool Frequency Per Day
0.95; 1.2; 1.5; 1.4 0.02 sig
SECONDARY
Stool Form/Consistency
2.5; 2.8; 3.4; 2.6 0.005 sig
SECONDARY
Stool Ease of Passage
3.5; 3.6; 3.8; 3.5 <0.04 sig
SECONDARY
Sense of Completely Emptying Bowels
86; 74; 73; 66
SECONDARY
Stool Frequency Per Week
2.1; 2.1; 4.0; 3.1
SECONDARY
Heart Rate Before and After Treatment
74; 76; 66; 75
SECONDARY
QTc Interval Before and After Treatment
428; 420; 415; 421

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.

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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00276406). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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