Ispaghula and Colonic Water Content
Condition: Healthy
Study type: Interventional

Summary: 
      Chronic constipation is a phenomenon which affects nearly 20% of the population worldwide.
      Bulking agents such as ispaghula are used as treatments, but only half of the patients are
      satisfied with the treatment. This highlights a need for better treatment options, which
      requires a deeper understanding of the gastrointestinal fate of the products. The GI MRI
      Research group at the University of Nottingham has been developing new, non-invasive magnetic
      resonance imaging (MRI) techniques to image the gastrointestinal tract. In collaboration with
      Ironwood Pharmaceuticals, the investigators now want to understand the gastrointestinal fate
      of an ispaghula treatment, and also to improve the understanding of MRI parameters when they
      are applied to the colon.
    

Detailed description: 
      The Rome III diagnostic criteria for constipation must include two or more of the following
      symptoms > 25 % of the time: straining, hard or lumpy stools, sense of incomplete evacuation,
      sensation of anorectal obstruction/blockage, the use of manual manoeuvres to facilitate
      defecation and fewer than 3 defecations per week. Treatments include osmotic laxatives such
      as polyethylene glycol and lactulose, stimulant laxatives such as bisacodyl, secretagogues
      like sodium docusate, and bulking agents such as psyllium.

      A better understanding of the modes of action of these drugs is required, in order to provide
      better treatment for chronic constipation. This is somewhat challenging; partly because
      techniques available to study intestinal contents are limited, and some are unpleasant for
      the patients. The GI MRI group at the University of Nottingham has recently developed a
      non-invasive, patient friendly MRI technique for studying the colon. The technique allows
      assessment of colonic volumes, the response to meals, motility of the colon and transit time
      of ingested meals. This technique has been used to demonstrate the laxative effect of
      mannitol and its subsequent reversal with loperamide.

      Using MRI, water provides a bright image on T2-weighted images in the small bowel, but the
      signal is rapidly lost once it reaches the colon. Pilot studies suggest that ispaghula; which
      is highly hygroscopic and can form a 1.5% gel with water, is able to maintain water in a form
      which produces bright images on T2-weighted scanning of the colon. The GI MRI group now want
      to confirm this pilot data by performing a placebo controlled trial of ispaghula husk in
      healthy volunteers, with the aim of further understanding the mode of action of bulking
      agents and further improve understanding of MRI parameters when applied to the colon. The
      aims will be achieved by performing a dose-finding mechanistic study in healthy volunteers,
      assessing their response to a test meal while taking either placebo, or 2 different doses of
      ispaghula. Stools will be collected, assessed for water content and compared to water content
      assessed from T2 weighted MRI. The studies will validate the current technique, optimise
      current MRI parameters and provide insights into the modes of action of ispaghula.
    

Intervention name(s): 7 g Ispaghula; 7 g placebo; 3.5g Ispaghula + 3.5 g placebo
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement
Other intervention name(s): Metamucil
Intervention MeSH terms: Psyllium; Calcium polycarbophil
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: Ispaghula; Gastrointestinal physiology; Gastrointestinal response to sugars; MRI; gastrointestinal; stomach; small bowel; colon