Functional Constipation Clinical Trial
Official title:
Mode of Action of Moviprep:Impact on Distribution of Intestinal Fluid and Colonic Microbiota
The University of Nottingham have been developing new, non-invasive magnetic resonance
imaging (MRI) techniques to image the bowel. Building on those studies the investigators
want to study, in healthy volunteers, the effects of purging on the colon. The investigators
plan two studies using their novel MRI techniques in healthy volunteers to demonstrate how
doses of a preparation designed to clean the bowel alters small and large bowel water
content and transit. The investigators will also define the changes induced in colonic
microbiota and how these are linked to changes in transit and the structure of colonic
contents. This experimental model is comparable to an episode of acute diarrhea, therefore
this study will also improve their understanding of the effects of diarrhea on bowel
physiology.
Following from the above study, the investigators would like to extend this study on
patients who have functional constipation and previously have not responded to conventional
laxatives.
Routine examinations of the colon including colonoscopy and barium enema widely carried out
in clinical practice require evacuation of colonic contents. This is most conveniently
carried out using osmotic laxatives the most widely used preparation being based on
polyethylene glycol such as Moviprep. When fully made up as 1 litre of Moviprep , it
provides 100 grams of polyethlene glycol '3350' with a measured osmolarity of around 530
mosmol/l. Being nonnutrient, this would be expected to rapidly leave the stomach and
generate a substantial inflow of fluid in the upper small intestine as water flows down the
osmotic gradient markedly increasing the small intestinal water content compared with
fasting.
Previous MRI studies using a Mannitol solution of 300 mosmols/l resulted in a small bowel
secretion of fluid increasing total small bowel water to nearly 400 mls after a 300 ml meal.
The investigators would anticipate a much larger increase after the hypertonic Moviprep. The
flush of small bowel fluid induced by mannitol produces a radical change in the
heterogeneous structure of the ascending colon as shown in our recent MRI images of the
colon before and after mannitol.
Contrary to expectation colonic contents are far from homogenous with a spatially organised
bacterial flora which others have described at a microscopic level which the investigators
are just beginning to demonstrate using their novel MRI techniques. The colon should be
regarded as a complex bioreactor which is spatially highly organised with a mucous layer
overlying the enterocytes, the outer layer of mucus containing a germinal layer with
bacteria which reseed the bioreactor when it is purged. The rate of recovery after purgation
with polyethylene glycol is said to be normally rapid as the intact germinal layer rapidly
recolonises but slower in certain patient groups though data is very limited as yet. The
anecdotal yet persuasive patient accounts of improvement in bowel function after colonic
lavage suggest that the reconstituted microbiota may be different, though this has yet to be
studied using modern techniques.
Until recently the investigators have had no way of noninvasive imaging this complex
structure but recent developments of high resolution MRI in Nottingham show that this is now
feasible. Pilot data demonstrates that purging removes the heterogeneous three dimensional
structure leaving homogeneous fluid contents with an intense proton signal. Just how this
impacts on the colonic microbiota is as yet unknown as there have been no studies to date
combining these novel approaches with new techniques now available for assessing the
microbiota.
Early culture-based assessments identify only a minority of all the faecal organisms present
and it is only in the last decade that methods based on assessment of microbial DNA have
evolved to make it possible to describe the full complexity of the faecal microbiota. PCR of
the highly conserved 16s ribosomal RNA gene shows the microbiota of individuals to be highly
complex and individualised. Similarity indices show similarities of around two thirds over a
7 week period in healthy controls while those developing acute diarrhoea due to radiation
enteritis show a marked reduction to just 26%. Similarly, HITChip analysis showed that
subjects with IBS had an unstable microbiota that was stabilised following a probiotic
intervention trial that improved the IBS symptom score. These techniques have yet to be
applied to subjects undergoing bowel purgation. Moreover, there are novel approaches to
identify the viability of the microbiota such as the use of specific probes that allow
discrimination between intact, damaged and dead cells in fecal samples.
;
Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Basic Science
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT04506801 -
The Effect of Probiotics on Functional Constipation in the Elderly
|
N/A | |
Completed |
NCT04620161 -
A Proof of Concept Study of Pradigastat in Patients With Functional Constipation
|
Phase 2 | |
Active, not recruiting |
NCT02361749 -
Botulinum Toxin Injection Versus Anal Myectomy in Management of Idiopathic Constipation
|
Phase 4 | |
Completed |
NCT03054805 -
The Effect of Probiotics on Constipation, and Intestinal Microflora in Children With Functional Constipation
|
Phase 4 | |
Not yet recruiting |
NCT01913665 -
The Effect of Bifidobacterium Lactis and Inulin on Functional Constipation
|
N/A | |
Completed |
NCT01348152 -
Effect of TU-100 in Patients With Functional Constipation
|
Phase 2 | |
Completed |
NCT01212146 -
Probiotic-enriched Artichoke in Functional Constipation
|
N/A | |
Completed |
NCT04231162 -
Effect of an 8-week Bifidobacterium Lactis HN019 Supplementation on Functional Constipation
|
N/A | |
Not yet recruiting |
NCT03639142 -
Dried Plums (Prunes) vs. Polyethylene Glycol 4000 for Treatment of Functional Constipation in Children
|
Phase 3 | |
Recruiting |
NCT04918329 -
Functional Digestive Disorders Observatory
|
||
Completed |
NCT02592200 -
Effect of Lactobacillus Gasseri DSM 27123 on Functional Constipation in Healthy Women
|
N/A | |
Completed |
NCT03707002 -
Effect of scFOS on Increase in Stool Frequency in Constipated People
|
N/A | |
Recruiting |
NCT06083311 -
The Efficacy of a Probiotic for Functional Constipation (FC)
|
N/A | |
Completed |
NCT04110145 -
Linaclotide Safety and Efficacy in 2 to 5-Year-Old Participants With Functional Constipation
|
Phase 2 | |
Recruiting |
NCT06196073 -
Visceral Osteopathy in Functional Constipation
|
N/A | |
Completed |
NCT04026113 -
Linaclotide Safety and Efficacy in Pediatric Participants, 6 to 17 Years of Age, With Irritable Bowel Syndrome With Constipation (IBS-C) or Functional Constipation (FC)
|
Phase 3 | |
Completed |
NCT02359396 -
A Randomized, Open-label, Three-arm Study of MZRW on Tolerability, Exposure and Pharmacokinetics
|
Phase 1 | |
Completed |
NCT01847950 -
Effects of scFOS on Stool Frequency in People With Functionnal Constipation
|
N/A | |
Recruiting |
NCT01274793 -
Trial for Quantity-Effect Relationship of Acupuncture With Two-ways Regulation to Treat Functional Enteropathy
|
Phase 1 | |
Active, not recruiting |
NCT04166058 -
Long-term Safety of Linaclotide in Pediatric Participants With FC or IBS-C
|
Phase 3 |