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MRI Assessment of Mode of Action of Bisacodyl, Single Dose (MODS)

Primary Purpose

Constipation

Status
Recruiting
Phase
Phase 4
Locations
United Kingdom
Study Type
Interventional
Intervention
Bisacodyl 5 milligram
Placebo oral tablet
Sponsored by
University of Nottingham
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Constipation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

I 01. Adult subjects that self-medicate with occasional laxative no more than 4 times in the month before eligibility confirmation

I 02. Meet Rome IV criteria for Chronic Constipation.

I 03. ≥18 years of age inclusive, at the time of signing the informed consent.

I 04. Screening diary confirms they experience at least 2 days in the 7 day diary with either hard stools (Bristol Stool form Score 1 or 2) or no bowel movement

I 05. BMI under or equal to 35 kg/m2

I 06. Female subjects of child bearing potential must have a negative urine pregnancy test at screening. Subjects of child bearing potential or with partners of child bearing potential must agree to use methods of medically acceptable forms of contraception during the study and for 90 days after completion of study drug, (e.g. implants, injectable, combined oral contraceptives, barrier methods, true abstinence (when this is in line with the preferred and usual lifestyle of the patient) or vasectomised partners).

I 07. Capable of giving signed informed consent as described in Appendix 1 (Section 10.1) which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria:

E 01. Known hypersensitivity or other contraindications to bisacodyl use: such as ileus, intestinal obstruction, acute abdominal conditions including appendicitis, acute inflammatory bowel diseases, and severe abdominal pain associated with nausea and vomiting; and severe dehydration or rare hereditary conditions that may be incompatible with an excipient of the product (galactose intolerance, e.g. galactosaemia, fructose intolerance.

E 02. Pregnancy and/or breast breast-feeding or positive urine pregnancy test History of known gastrointestinal organic disease (i.e. celiac disease, inflammatory bowel diseases).

E 03. A positive diagnosis of irritable bowel syndrome based on the Rome IV criteria questionnaire which requires the patient to experience abdominal pain at least weekly

E 04. Reported history of previous major abdominal surgery (excluding appendectomy and cholecystectomy)

E 05. Any medical condition making participation potentially compromising the participation in the study (e.g. diabetes mellitus, respiratory disease limiting ability to lie in the scanner, known allergy to one of the food products) as per investigator's judgment

E 06. Contraindications for MRI scanning i.e. metallic implants, pacemakers, history of metallic foreign body in eye(s) and penetrating eye injury

E 07. Any condition incompatible with the patient's participation to the study as per investigator's judgment.

E 08. Not willing or able agree to dietary restrictions required in 24 hours before each MRI study day

E 09. Anticipate need for antibiotics intake during the study.

E 10. Unwilling to stop probiotics for the duration of the study period

E 11. Unable/ not willing to stop drugs known to alter GI motility including, regular loperamide, antispasmodics, (e.g. buscopan, mebeverine, peppermint oil, alverine citrate), eluxadoline opiates, monoamine oxidase inhibitors, phenothiazines, benzodiazepines, calcium channel antagonists for the duration of the study (Selective serotonin reuptake inhibitors and low dose tricyclic antidepressants (< 30mg amitriptyline or 50mg nortriptyline) will be recorded but provided dose is stable, will not be an exclusion criteria).

E 12. Having taken part in a research study within 3 months

Sites / Locations

  • University of NottinghamRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

bisacodyl

placebo

Arm Description

5 mg bisacodyl, one tablet once

placebo, one tablet once

Outcomes

Primary Outcome Measures

Consistency of chyme in ascending colon
as measured by MRI (T1)

Secondary Outcome Measures

Longer term consistency of chyme in ascending colon
as measured by MRI (T1)
Gut motor function
colonic and small bowel motility as measured by MRI
Small intestinal water content
as measured by MRI
Colon volumes
as measured by MRI
Speed of whole gut transit
weighted average position score of transit markers

Full Information

First Posted
October 17, 2019
Last Updated
May 23, 2022
Sponsor
University of Nottingham
Collaborators
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT04132661
Brief Title
MRI Assessment of Mode of Action of Bisacodyl, Single Dose
Acronym
MODS
Official Title
A Phase IV, Crossover, Randomized, Double Blind and Placebo-controlled Clinical Trial to Evaluate the Mode of Action of a Single Dose of Bisacodyl in Subjects With Occasional Constipation
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 25, 2020 (Actual)
Primary Completion Date
July 31, 2022 (Anticipated)
Study Completion Date
July 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Nottingham
Collaborators
Sanofi

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Constipation remains an important unmet medical need. Patients are currently often dissatisfied with treatment, because of lack of predictability of the laxative, side effects (mainly abdominal pain) and perceived decrease of efficacy with time. A recent systematic review of a range of laxatives reported that bisacodyl increases the number of complete spontaneous bowel movements statistically significant compared to placebo. Recently non-invasive Magnetic Resonance Imaging (MRI) techniques have been developed to assess small intestinal fluid distribution, transit and motility as well as colonic fluid, volumes and motility in healthy volunteers and constipated subjects. Other laxatives such as movecol and ispaghula have been investigated using this methodology. This study will use these novel techniques to further characterize bisacodyl's mode of action. This study is intended to assess the effect of a single-dose of bisacodyl on the gut motor function and its effect on water distribution within the small and large intestine in subjects with occasional constipation by MRI. It may allow better understanding of the relative importance of both the secretory and the prokinetic effect of bisacodyl. Since bisacodyl is often used by self-medicating people with constipation it is proposed to study subjects suffering from occasional constipation. As such subjects often take the drug intermittently it would be of interest to study both the acute response after single dose and the response after several days of treatment to see if this alters the response. The current study will be performed as a cross-over with 2-period and 2-treatment (bisacodyl/placebo), for assessing the effects over of a single-dose of 5mg bisacodyl. Evaluations will be performed after one single dose of bisacodyl or placebo in two different time periods, separated by a 2 week washout period between end of period 1 and start of period 2. The study will recruit individuals ≥18yrs from the general public who consider themselves as suffering from occasional constipation and who self-medicate with an occasional over-the counter (OTC) laxative, not more than once a week. Up to 18 adult healthy subjects will be recruited to ensure 10 evaluable subjects. An evaluable subject is defined as participant having the primary endpoint assessed (ascending colon T1 300, 375, and 450 minutes correctly evaluated) for the two periods of the crossover.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Constipation

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Model Description
Phase IV, single center, double blind, randomized (1:1 ratio), two arms (bisacodyl and placebo), single-dose, and crossover clinical trial.
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
The study is a double blind study with a randomization ratio 1:1. The subjects, the investigator and the Sanofi team will be blinded to the treatment sequences allocation until the database lock. The medicinal product and placebo are indistinguishable using exactly the same packing and form.
Allocation
Randomized
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
bisacodyl
Arm Type
Experimental
Arm Description
5 mg bisacodyl, one tablet once
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
placebo, one tablet once
Intervention Type
Drug
Intervention Name(s)
Bisacodyl 5 milligram
Other Intervention Name(s)
dulcolax
Intervention Description
one single dose
Intervention Type
Drug
Intervention Name(s)
Placebo oral tablet
Intervention Description
one single dose
Primary Outcome Measure Information:
Title
Consistency of chyme in ascending colon
Description
as measured by MRI (T1)
Time Frame
Area under the curve 300-450 minutes after single intake of intervention
Secondary Outcome Measure Information:
Title
Longer term consistency of chyme in ascending colon
Description
as measured by MRI (T1)
Time Frame
24 hours after drug intake
Title
Gut motor function
Description
colonic and small bowel motility as measured by MRI
Time Frame
0-150 and 150-450 minutes after single intake of intervention
Title
Small intestinal water content
Description
as measured by MRI
Time Frame
0-150 and 150-450 minutes after single intake of intervention
Title
Colon volumes
Description
as measured by MRI
Time Frame
0-150 and 150-450 minutes after single intake of intervention
Title
Speed of whole gut transit
Description
weighted average position score of transit markers
Time Frame
at 450 minutes and 24 hours after transit marker and study drug intake

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: I 01. Adult subjects that self-medicate with occasional laxative no more than 4 times in the month before eligibility confirmation I 02. Meet Rome IV criteria for Chronic Constipation. I 03. ≥18 years of age inclusive, at the time of signing the informed consent. I 04. Screening diary confirms they experience at least 2 days in the 7 day diary with either hard stools (Bristol Stool form Score 1 or 2) or no bowel movement I 05. BMI under or equal to 35 kg/m2 I 06. Female subjects of child bearing potential must have a negative urine pregnancy test at screening. Subjects of child bearing potential or with partners of child bearing potential must agree to use methods of medically acceptable forms of contraception during the study and for 90 days after completion of study drug, (e.g. implants, injectable, combined oral contraceptives, barrier methods, true abstinence (when this is in line with the preferred and usual lifestyle of the patient) or vasectomised partners). I 07. Capable of giving signed informed consent as described in Appendix 1 (Section 10.1) which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Exclusion Criteria: E 01. Known hypersensitivity or other contraindications to bisacodyl use: such as ileus, intestinal obstruction, acute abdominal conditions including appendicitis, acute inflammatory bowel diseases, and severe abdominal pain associated with nausea and vomiting; and severe dehydration or rare hereditary conditions that may be incompatible with an excipient of the product (galactose intolerance, e.g. galactosaemia, fructose intolerance. E 02. Pregnancy and/or breast breast-feeding or positive urine pregnancy test History of known gastrointestinal organic disease (i.e. celiac disease, inflammatory bowel diseases). E 03. A positive diagnosis of irritable bowel syndrome based on the Rome IV criteria questionnaire which requires the patient to experience abdominal pain at least weekly E 04. Reported history of previous major abdominal surgery (excluding appendectomy and cholecystectomy) E 05. Any medical condition making participation potentially compromising the participation in the study (e.g. diabetes mellitus, respiratory disease limiting ability to lie in the scanner, known allergy to one of the food products) as per investigator's judgment E 06. Contraindications for MRI scanning i.e. metallic implants, pacemakers, history of metallic foreign body in eye(s) and penetrating eye injury E 07. Any condition incompatible with the patient's participation to the study as per investigator's judgment. E 08. Not willing or able agree to dietary restrictions required in 24 hours before each MRI study day E 09. Anticipate need for antibiotics intake during the study. E 10. Unwilling to stop probiotics for the duration of the study period E 11. Unable/ not willing to stop drugs known to alter GI motility including, regular loperamide, antispasmodics, (e.g. buscopan, mebeverine, peppermint oil, alverine citrate), eluxadoline opiates, monoamine oxidase inhibitors, phenothiazines, benzodiazepines, calcium channel antagonists for the duration of the study (Selective serotonin reuptake inhibitors and low dose tricyclic antidepressants (< 30mg amitriptyline or 50mg nortriptyline) will be recorded but provided dose is stable, will not be an exclusion criteria). E 12. Having taken part in a research study within 3 months
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Robin Spiller, PhD
Phone
+441158231090
Email
mszrs@exmail.nottingham.ac.uk
First Name & Middle Initial & Last Name or Official Title & Degree
Neele Dellschaft, PhD
Phone
+44 115 8467774
Email
neele.dellschaft@nottingham.ac.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robin Spiller, PhD
Organizational Affiliation
University of Nottingham
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Nottingham
City
Nottingham
State/Province
Nottinghamshire
ZIP/Postal Code
NG7 2RD
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
For those journals that request sharing of the analyzable data sets that are reported in the publication, interested researchers are directed to submit their request to clinicalstudydatarequest.com.

Learn more about this trial

MRI Assessment of Mode of Action of Bisacodyl, Single Dose

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