Effect of Kiwifruit on Gastrointestinal Fluid Distribution and Transit in Healthy Volunteers

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.