Use of Pyridostigmine for Constipation in Diabetics

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Adil Bharucha, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00276406
First received: January 11, 2006
Last updated: November 2, 2012
Last verified: November 2012
Results First Received: November 2, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Constipation
Diabetes Mellitus
Colonic Transit
Gastric Emptying
Interventions: Drug: Pyridostigmine
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were recruited from Mayo Clinic in Rochester, Minnesota and the study was conducted at between May 2006 and October 2010.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
68 patients were assessed for eligibility. 24 were ineligible. 13 were eligible but declined to participate in the study. One patient consented but was withdrawn because of severe hyperglycemia during the baseline period. 30 were enrolled and completed all study procedures.

Reporting Groups
  Description
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.
Placebo Placebo (sham) capsules, matching the appearance of the active drug comparator and taken tid.

Participant Flow:   Overall Study
    Pyridostigmine     Placebo  
STARTED     16     14  
COMPLETED     16 [1]   14  
NOT COMPLETED     0     0  
[1] 14 of 16 subjects tolerated 360mg daily, while 2 of 16 tolerated 180mg daily.



  Baseline Characteristics
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Reporting Groups
  Description
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.
Placebo Placebo (sham) capsules, matching the appearance of the active drug comparator and taken tid.
Total Total of all reporting groups

Baseline Measures
    Pyridostigmine     Placebo     Total  
Number of Participants  
[units: participants]
  16     14     30  
Age  
[units: years]
Mean ± Standard Deviation
  48.5  ± 11.4     52.1  ± 11.3     50.2  ± 11.3  
Gender  
[units: participants]
     
Female     13     9     22  
Male     3     5     8  
Region of Enrollment  
[units: participants]
     
United States     16     14     30  
Body Mass Index [1]
[units: kilograms/meter^2]
Mean ± Standard Deviation
  27.9  ± 4.4     31.6  ± 6.0     29.7  ± 5.5  
Hemoglobin A1c [2]
[units: Percentage]
Mean ± Standard Deviation
  8.1  ± 1.7     7.7  ± 1.2     7.9  ± 0.3  
Subjects with diabetic retinopathy [3]
[units: Participants]
  9     7     16  
Geometric Center (GC) of Colonic transit [4]
[units: Units on a scale]
Mean ± Standard Deviation
     
Geometric Center of Colonic Transit at 24 hr (GC24     1.96  ± 0.71     1.98  ± 0.62     1.97  ± 0.66  
Geometric Center of Colonic Transit at 48 hr (GC48     2.92  ± 0.89     2.97  ± 1.00     2.94  ± 0.93  
[1] Body Mass Index (BMI) is a health index for comparing weight to height. BMI is a person's weight in kilograms (kg) divided by his or her height in meters squared. The body mass index is an indication if a person is at a suitable weight for his height on an approximation of body fat. A body mass index of under 20 is considered to be underweight, while a body mass index between 20 to 25 is considered healthy. A body mass index in the range of 25 to 30 is regarded as overweight. A body mass index over 30 is regarded as obese.
[2] Hemoglobin A1c (HgA1c) or glycolated hemoglobin is a laboratory test of blood which provides a measure the average blood glucose (sugar) levels for the prior 3 month period.
[3]

Diabetic retinopathy is a condition of the eye caused by diabetes, caused by abnormal blood vessel growth, which invades the retina and can cause reduced vision and blindness.

Note: because not all subjects had retinopathy, the number of subjects with retinopathy in each arm will not match the overall number of subjects enrolled in each arm.

[4] The scintigraphic method is used to measure movement of large intestine contents. A radio-labeled isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule taken by mouth with a meal. Abdominal anterior and posterior gamma images are taken hourly. 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.



  Outcome Measures
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1.  Primary:   Colonic Geometric Center at 24 Hours (GC24) Measured by Scintigraphy   [ Time Frame: Baseline period (days 7-9 ), Treatment period (days 14-17) ]

2.  Primary:   Ascending Colon Emptying Half-time (AC t1/2) Measured in Hours   [ Time Frame: Baseline period (days 7-9 ), Treatment period (days 14-17) ]

3.  Secondary:   Gastric Emptying Half-time (GE t1/2)   [ Time Frame: Baseline period (9 days), Treatment period (7 days) ]

4.  Secondary:   Colonic Filling at 6 Hours   [ Time Frame: Baseline period (9 days), Treatment period (7 days) ]

5.  Secondary:   Colonic Geometric Center at 48 Hours (GC48) as Measured by Scintigraphy   [ Time Frame: Baseline period (days 7-9 ), Treatment period (days 14-17) ]

6.  Secondary:   Stool Frequency Per Day   [ Time Frame: Daily during baseline period (9 days), Treatment period (7 days) ]

7.  Secondary:   Stool Form/Consistency   [ Time Frame: Daily during baseline period (9 days), Treatment period (7 days) ]

8.  Secondary:   Stool Ease of Passage   [ Time Frame: Daily during baseline period (9 days), Treatment period (7 days) ]

9.  Secondary:   Sense of Completely Emptying Bowels   [ Time Frame: Daily during baseline period (9 days), Treatment period (7 days) ]

10.  Secondary:   Stool Frequency Per Week   [ Time Frame: Daily during baseline period (9 days), Treatment period (7 days) ]

11.  Secondary:   Heart Rate Before and After Treatment   [ Time Frame: Baseline period (9 days), Treatment period (7 days) ]

12.  Secondary:   QTc Interval Before and After Treatment   [ Time Frame: Baseline period (9 days), Treatment period (7 days) ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Adil E. Bharucha, MD
Organization: Mayo Clinic
phone: 507-284-6439
e-mail: bharucha.adil@mayo.edu


Publications of Results:

Responsible Party: Adil Bharucha, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00276406     History of Changes
Other Study ID Numbers: 05-004037, UL1RR024150-01, P01DK068055
Study First Received: January 11, 2006
Results First Received: November 2, 2012
Last Updated: November 2, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board