Mode of Action of Moviprep
Condition: Functional Constipation; Irritable Bowel Syndrome Characterized by Constipation
MeSH terms: Irritable Bowel Syndrome; Constipation
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Polyethyleneglycol
Intervention type(s): Drug
Intervention description(s): Group 1 sachet's A and B made up to 1 litre with tap water once on day 1 and once on day 2. Group 2 2x sachet's A and B made up to 2 litres with tap water on day 1. Group 3 sachet's A and B made up to 1 litre with tap water once on day 1.
Other intervention name(s): Macrogol 3350; Moviprep
Intervention MeSH terms: Polyethylene glycol 3350
Allocation: Non-Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Primary purpose: Basic Science