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

NCT ID: NCT03303417

Last Updated: 2019-06-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-27
• Study Completion Date: 2018-06-01

Brief 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.

Conditions

Constipation; Diet Modification

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Kiwifruit

Participants asked to consume 2 kiwifruit twice a day for 3 days before undergoing MRI Scan

Group Type: EXPERIMENTAL

MRI Scan

Intervention Type: DIAGNOSTIC_TEST

Participants will undergo hourly MRI scans on day 3 to assess bowel fluid content

Kiwifruit

Intervention Type: OTHER

Kiwifruit

Control

Participants asked to consume a calorie-matched sugar drink twice a day for 3 days before undergoing MRI Scan

Group Type: PLACEBO_COMPARATOR

MRI Scan

Intervention Type: DIAGNOSTIC_TEST

Participants will undergo hourly MRI scans on day 3 to assess bowel fluid content

calorie-matched sugar drink

Intervention Type: OTHER

calorie-matched sugar drink

Interventions

MRI Scan

Participants will undergo hourly MRI scans on day 3 to assess bowel fluid content

Intervention Type: DIAGNOSTIC_TEST

Kiwifruit

Kiwifruit

Intervention Type: OTHER

calorie-matched sugar drink

calorie-matched sugar drink

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Healthy volunteers scoring within the normal range for bowel symptoms as assessed using the GSRS, aged 18-65 years.

Exclusion Criteria

1. Inability to discontinue medication likely to alter GI transit.

2. Previous gastrointestinal surgery (excluding cholecystectomy and appendectomy).

3. Known inflammatory bowel disease, coeliac disease.

4. Known intolerance of kiwifruit.

5. Inability to discontinue drugs likely to alter gut transit.

6. Subjects considered by the investigator unlikely to comply with study protocol.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Zespri International Limited

INDUSTRY

Sponsor Role: collaborator

University of Nottingham

OTHER

Sponsor Role: lead

Responsible Party

Robin Spiller

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Nottingham

Nottingham, Nottinghamshire, United Kingdom

Countries

United Kingdom

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

A200317

Identifier Type: -

Identifier Source: org_study_id