ConstipationPhase 1/2NCT00276406
Use of Pyridostigmine for Constipation in Diabetics
A Phase 1/2 study testing Pyridostigmine in people with Constipation and Diabetes Mellitus, run by Mayo Clinic at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Constipation, Diabetes Mellitus, Colonic Transit
- What is being tested?
- Pyridostigmine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- May 2006to Oct 2010
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pyridostigmine in Diabetics With Constipation: Randomized, Placebo-controlled, Double-blind Trial
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.
Read the 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
- Being tested
- Pyridostigmine, Placebo
- Medical subject headings
- Constipation, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PyridostigmineDrug
Also called Mestinon
Pyridostigmine will be started at (60mg) tid, increased over 10 days to 120 mg tid, and maintained at that dose for 7 days.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Pyridostigmine |
| Placebo | Placebo comparator | Placebo (sham) capsules, matching the appearance of the active drug comparator and taken TID. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline period (days 7-9 ), Treatment period (days 14-17)
Secondary outcomes (10)
Gastric Emptying Half-time (GE t1/2)
The measure of time for 50 percent of a radio-labeled meal to empty from the stomach.
Measured: Baseline period (9 days), Treatment period (7 days)
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.
Measured: Baseline period (9 days), Treatment period (7 days)
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.
Measured: Baseline period (days 7-9 ), Treatment period (days 14-17)
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.
Measured: Daily during baseline period (9 days), Treatment period (7 days)
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.
Measured: Daily during baseline period (9 days), Treatment period (7 days)
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.
Measured: Daily during baseline period (9 days), Treatment period (7 days)
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.
Measured: Daily during baseline period (9 days), Treatment period (7 days)
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.
Measured: Daily during baseline period (9 days), Treatment period (7 days)
Heart Rate Before and After Treatment
Heart rate is the number of beats per minute, as recording on an Electrocardiogram (ECG).
Measured: Baseline period (9 days), Treatment period (7 days)
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).
Measured: Baseline period (9 days), Treatment period (7 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2006 (estimated)
- Study startMay 2006
- Primary completionOct 2010
- Study completionOct 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ConstipationStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Center for Research Resources (NCRR)
- Responsible party
- Principal investigator, Adil Bharucha, Mayo Clinic
- Investigators
- Adil E. Bharucha, MBBS, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00276406
- Sponsor's protocol ID
- 05-004037
- Other IDs
- UL1RR024150-01, P01DK068055
- Status last verified
- Nov 2012
- First submitted
- 11 Jan 2006
- Last updated
- 30 Nov 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 22677718
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pyridostigmine in Diabetics With Constipation: Randomized, Placebo-controlled, Double-blind Trial
- ClinicalTrials.gov ID
- NCT00276406
- Acronym / sponsor ID
- 05-004037
- Conditions
- Constipation, Diabetes Mellitus, Colonic Transit, Gastric Emptying
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Center for Research Resources (NCRR)
- Study start
- May 2006
- Primary completion
- Oct 2010 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 13 Jan 2006 (estimated)
- Results
- Posted 30 Nov 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pyridostigmine | Experimental | Drug: PyridostigmineOral 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 comparator | Drug: PlaceboPlacebo (sham) capsules, matching the appearance of the active drug comparator and taken TID. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (14 listed)
- 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:
- 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))
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PyridostigmineAlso: MestinonPyridostigmine will be started at (60mg) tid, increased over 10 days to 120 mg tid, and maintained at that dose for 7 days. | Drug | Pyridostigmine |
| PlaceboIf 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. | Drug | Placebo |
Primary outcome
Colonic Geometric Center at 24 Hours (GC24) Measured by Scintigraphy
Time frame: Baseline period (days 7-9 ), Treatment period (days 14-17)
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.
Ascending Colon Emptying Half-time (AC t1/2) Measured in Hours
Time frame: Baseline period (days 7-9 ), Treatment period (days 14-17)
Calculated by linear interpolation of values on the AC emptying curve.
10 secondary outcomes
Gastric Emptying Half-time (GE t1/2)
Time frame: Baseline period (9 days), Treatment period (7 days)
Colonic Filling at 6 Hours
Time frame: Baseline period (9 days), Treatment period (7 days)
Colonic Geometric Center at 48 Hours (GC48) as Measured by Scintigraphy
Time frame: Baseline period (days 7-9 ), Treatment period (days 14-17)
Stool Frequency Per Day
Time frame: Daily during baseline period (9 days), Treatment period (7 days)
Stool Form/Consistency
Time frame: Daily during baseline period (9 days), Treatment period (7 days)
Stool Ease of Passage
Time frame: Daily during baseline period (9 days), Treatment period (7 days)
Sense of Completely Emptying Bowels
Time frame: Daily during baseline period (9 days), Treatment period (7 days)
Stool Frequency Per Week
Time frame: Daily during baseline period (9 days), Treatment period (7 days)
Heart Rate Before and After Treatment
Time frame: Baseline period (9 days), Treatment period (7 days)
QTc Interval Before and After Treatment
Time frame: Baseline period (9 days), Treatment period (7 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22677718Bharucha 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.
Related trials for Constipation
Recruiting
Effects of a Prebiotic-Probiotic Combination on Constipation Symptoms and Quality of Life
Constipation, Abdominal Pain
RecruitingPhase 2
A Study of Brenipatide (LY3537031) in Participants With Irritable Bowel Syndrome-Constipation (IBS-C)
Irritable Bowel Syndrome, Constipation
Recruiting
Outcome Research in Bowel Irrigation Techniques for the Treatment of Chronic Constipation and/or Faecal Incontinence
Faecal Incontinence, Chronic Constipation
Active, not recruitingPhase 2
This is a Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel-group Study of the Efficacy and Safety of 2 Weight-based Treatment Groups of Plecanatide Versus Placebo in Children and Adolescent Participants 6 to Less Than 18 Years of Age With FC
Functional Constipation (FC)
Not yet recruiting
Acupuncture Combined With Transcutaneous Electrical Acupoint Stimulation for Constipation-Predominant Irritable Bowel Syndrome With Anxiety State
IBS, Constipation Predominant, Anxiety State
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adil E. Bharucha, MBBS, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pyridostigmine in people with Constipation and Diabetes Mellitus, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Nov 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Nov 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Colonic Geometric Center at 24 Hours (GC24) Measured by Scintigraphy (time frame: Baseline period (days 7-9 ), Treatment period (days 14-17)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00276406, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Nov 2012.