Effect of Kiwifruit on Gastrointestinal Fluid Distribution and Transit in Healthy Volunteers
Condition: Constipation; Diet Modification
MeSH terms: Constipation
Study type: Interventional

Summary: 
      Constipation is a widespread and common problem in which a person finds it difficult and/or
      painful to open their bowels. The current treatment is the use of medications called
      laxatives. Kiwifruit is a widely available food that has been shown to possess some laxative
      properties. The cause of this is unknown. Non-invasive medical imaging techniques such as
      Magnetic Resonance Imaging now allow taking pictures of the gut and its contents. The
      Nottingham GI MRI research group specialises in these techniques and in this study use such
      images to assess the changes induced in the gut contents by kiwifruit to improve
      understanding of how it helps patients with constipation.

      The volunteers will be asked to undergo 2 studies in which they take either kiwifruit or
      placebo (sugary drink) two times a day for 2 days and then spend a study day where will they
      will be fed some more kiwifruit/placebo and some normal food and image their gut at
      intervals. Participants will be asked to complete a stool diary to determine if they
      experience a laxative effect.
    

Detailed description: 
      1. Background. Chronic constipation affects approximately 17% of the population worldwide
           and remains an important unmet need since patients are currently often dissatisfied with
           treatment Current treatments which stimulate propulsive colonic motility or osmotic
           laxatives are successful in increasing stool frequency but are often associated with
           bloating, cramps and abdominal discomfort. Furthermore, such powerful treatments taken
           intermittently often create abnormal colonic contents and may result in alternation
           between diarrhoea and no stools. Many patients would benefit from a less powerful
           treatment which could be taken daily. Kiwifruit offer such an alternative and have been
           shown to increase stool volume and frequency. The mode of action however is unclear.
           Kiwi is 3% fibre (approximately 1/3 insoluble) and contains around 3% nonstarch
           polysaccharide including pectins, hemicellulose and cellulose, with high water holding
           capacity 1.5 times that of ispaghula, a commonly used laxative. Using recently developed
           and validated novel non-invasive MRI techniques, the University can assess transit and
           fluid distribution in the small intestine [4]. The University has also developed methods
           to assess colonic fluid, volumes and motility.

        2. Aims. To assess the effect of kiwifruit on gastrointestinal fluid distribution.

        3. Experimental protocol and methods. A randomised, placebo controlled, 2-way cross-over
           study in N=15 healthy volunteers assessing the response (versus baseline values) of 2
           kiwifruit b.d vs placebo (28 gm maltodextrin drink providing 120kcal equal to that of 2
           kiwifruit) daily. After a screening visit to confirm eligibility, study subjects will be
           randomised as to the test product schedule. Subjects will complete a daily stool diary
           documenting stool frequency and consistency using the Bristol Stool Form Scale. They
           will consume the test product allocated starting on Day 4. At 9 am of the morning of Day
           5 they will ingest 5 MRI transit markers as described below and note the time of
           ingestion. The markers will be imaged at 24 hours (baseline scan of Day 6). On the main
           study day, the subjects will arrive fasted overnight and undergo fasting scans before
           consuming that day's allocated test product with 250ml of water. After 30 minutes
           considered to be Time =0 they will consume a standard rice pudding meal as used in
           previous studies. They will then undergo serial scanning hourly for 7 hours taking the
           second dose of test product plus 250ml water at Time 180 minutes. The third dose is
           taken at 320 minutes followed at 380 minutes by a second, larger test meal consisting of
           400 g microwaveable macaroni cheese ready meal (Sainsbury), 100 g cheesecake slice
           (Sainsbury), and 250 mL bottled still water. The second test meal provides approx. 1000
           kcal. The final scan will at time 420 minutes to assess the effect of ileal emptying on
           gastrointestinal fluid distribution. They will then be allowed home. There will be 2
           weeks between studies to ensure return to baseline. At the end of the study a further 3
           participants will be scanned in exactly the same protocol however at a lower dose of
           kiwifruit (2 fruit once daily) to determine if the effect is still visible.

        4. Measurable end points/statistical power of the study. Primary endpoint: Effect of
           Kiwifruit on Ascending colon T1 area under curve from time 0-420.

      Secondary endpoints: Effect of Kiwifruit on the following measures both fasting and
      postprandial AUC 0-420 minutes: 1) small bowel water content 2) ascending (AC), transverse
      (TC) and descending (DC) colonic volumes. 3) Transit of markers through gut as assessed by
      the weighted position score at 24 h (WAPS24) 4) Colonic motility 5) Gastric emptying of test
      meal 6) T1 of AC and DC. Pilot data with a standard laxative dose of ispaghula 7g t.d.s.
      showed a change of T1 AUC 0-360 of mean (SD) 88 (55) sec.min . Using this data n=15 healthy
      volunteers will give us >90% power to detect such a difference.
    

Intervention name(s): MRI Scan; Kiwifruit; calorie-matched sugar drink
Intervention type(s): Diagnostic Test; Other; Other
Intervention description(s): Participants will undergo hourly MRI scans on day 3 to assess bowel fluid content; Kiwifruit; calorie-matched sugar drink
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Kiwifruit