Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001060730
Ethics application status
Approved
Date submitted
26/07/2022
Date registered
29/07/2022
Date last updated
15/04/2024
Date data sharing statement initially provided
29/07/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Kiwifruit Ingestion to Normalise Gut Symptoms (Gastric) in individuals with Functional Constipation (FC) or Constipation-predominant Irritable Bowel Syndrome (IBS-C)
Scientific title
An open-label intervention study to determine if kiwifruit ingestion can normalise gastrointestinal symptoms in individuals with Functional Constipation (FC) or Constipation-predominant Irritable Bowel Syndrome (IBS-C).
Secondary ID [1] 307651 0
HVNT2HD GRKF RCT
Universal Trial Number (UTN)
Trial acronym
KINGS Gastric
Linked study record
ACTRN12621000621819. This record is a sub-study of this study.

Health condition
Health condition(s) or problem(s) studied:
Functional constipation 327159 0
Constipation-predominant irritable bowel syndrome (IBS-C) 327160 0
Condition category
Condition code
Oral and Gastrointestinal 324293 324293 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The main intervention will consist of two Zespri™ green kiwifruit per day, which will be eaten orally without the skin for 4 weeks.
The study duration is a nominal total of 8 weeks; 2-week lead-in phase, 4-week intervention phase, and final 2-week follow-up phase.
The 2-weeks lead-in phase requires participants to record their bowel motion on a developed app every day (until study completion); complete a questionnaire in regards to their socioeconomic status and general wellbeing, complete a non-consecutive 3-day food diary and a fibre-specific food frequency questionnaire (2nd week of lead-in phase). Participants will consume a provided evening standardised meal, provide a faecal sample and fast overnight for 9 hours one day prior to their baseline visit (end of 2nd week of lead-in phase). Participants will provide a blood sample, complete a set of questionnaires in regards to their mental and physical health, general well-being, and clinical variables, undergo physiome during their baseline visit (end of 2nd week of lead-in phase).
Participants (constipation group and healthy control group) will consume two Zespri® green kiwifruit per day throughout the 4 weeks intervention. The fruits will be provided by the research team in bulk for the participants to take home. Compliance will be monitored by checklist.
Participants will repeat all of the aforementioned baseline visit procedures before and on their post-intervention visit. Prior to the follow up visit, participants will again complete the same set of questionnaires, provide a faecal sample, fast overnight for 9 hours and provide a fasted blood sample. Participants will receive their reimbursements (gift vouchers) after each visits. Attendance of clinic visits and completion of questionnaire will be assessed to measure the adherence of participants.
Intervention code [1] 324106 0
Treatment: Other
Comparator / control treatment
The same intervention (two Zespri™ green kiwifruit per day for 4 weeks) is given to participants in the healthy control group.
Control group
Active

Outcomes
Primary outcome [1] 332108 0
A change in digestive comfort as indicated by a change in abdominal pain relief as measured by the Gastrointestinal Symptom Rating Scale (GSRS).
The GSRS is a validated instrument with a 1-week recall that assesses symptom severity using a 7-grade Likert scale, ranging from 1 (“no discomfort at all”) to 7 (“very severe discomfort”). An abdominal pain responder will be one who reports a reduction in pain of at least 30% from baseline.
Timepoint [1] 332108 0
Participants will fill out GSRS questionnaires at baseline (end of 2nd week of lead-in phase), immediately after the intervention concluded (4th week), and at follow-up (2 weeks after the intervention concluded).
Secondary outcome [1] 412219 0
A change in complete spontaneous bowel movements using a bowel habit diary app.
Timepoint [1] 412219 0
Daily starting from 2 weeks prior to intervention commencement and finishing at 2 weeks after the intervention has concluded.
Secondary outcome [2] 412220 0
A change in classification during the trial and changes to upper gastrointestinal symptoms assessed as a composite outcome using the validated Rome IV questionnaire for Adult Functional Gastrointestinal Disorders (FGIDs) (R4DQ)
Timepoint [2] 412220 0
Collected at enrolment, baseline (2nd week of lead-in phase), immediately after the intervention concluded (4th week), and at follow-up (2 weeks after the intervention concluded).
Secondary outcome [3] 412221 0
To determine habitual food intake before and after the intervention using a three-day food diary
Timepoint [3] 412221 0
One week prior to baseline (2nd week of lead in-phase) and 4th week of the study intervention.
Secondary outcome [4] 412222 0
A change in habitual fibre intake using the validated Inulin and Oligofructose Food Frequency Questionnaire.
Timepoint [4] 412222 0
One week prior to baseline (2nd week of lead in-phase) and 4th week of the study intervention.
Secondary outcome [5] 412223 0
A change in gastrointestinal symptoms using a (validated) Structured Assessment of Gastrointestinal Symptoms (SAGIS)
Timepoint [5] 412223 0
At baseline (end of 2nd week of lead-in phase), immediately after the intervention concluded (end of 4th week), and at follow-up (2 weeks after the intervention concluded).
Secondary outcome [6] 412224 0
A change in gastrointestinal symptoms specifically bowel movements, pain, bloating, reflux, assessed as a composite outcome using the Patient-Reported Outcomes Measurement Information System Questionnaire (PROMIS Gastrointestinal)
Timepoint [6] 412224 0
At baseline (end of 2nd week of lead-in phase), immediately after the intervention concluded (end of 4th week), and at follow-up (2 weeks after the intervention concluded).
Secondary outcome [7] 412225 0
A change in IBS symptoms and its treatment using Irritable Bowel Syndrome- Quality of Life survey (IBS-QOL).
Timepoint [7] 412225 0
At baseline (end of 2nd week of lead-in phase), immediately after the intervention concluded (end of 4th week), and at follow-up (2 weeks after the intervention concluded).
Secondary outcome [8] 412226 0
A change in anxiety scores using Patient-Reported Outcomes Measurement Information System Questionnaire (PROMIS Anxiety)
Timepoint [8] 412226 0
At baseline (end of 2nd week of lead-in phase), immediately after the intervention concluded (end of 4th week), and at follow-up (2 weeks after the intervention concluded).
Secondary outcome [9] 412227 0
A change in depression scores using Patient-Reported Outcomes Measurement Information System Questionnaire (PROMIS Depression)
Timepoint [9] 412227 0
At baseline (end of 2nd week of lead-in phase), immediately after the intervention concluded (end of 4th week), and at follow-up (2 weeks after the intervention concluded).
Secondary outcome [10] 412228 0
A change in the faecal metabolome, metagenome (DNAseq), metagenome assemblies, bile and organic acid production assessed as a composite outcome from faecal sample.
Timepoint [10] 412228 0
At baseline (end of 2nd week of lead-in phase), immediately after the intervention concluded (end of 4th week), and at follow-up (2 weeks after the intervention concluded).
Secondary outcome [11] 412229 0
A change in plasma metabolome and neurotransmitters assessed as an exploratory composite outcome by collecting plasma samples.
Timepoint [11] 412229 0
At baseline (end of 2nd week of lead-in phase), immediately after the intervention concluded (end of 4th week), and at follow-up (2 weeks after the intervention concluded).
Secondary outcome [12] 412231 0
Changes in stomach gastric myoelectrical activity assessed as a composite outcome measured by body gastric surface mapping.
Timepoint [12] 412231 0
At baseline (end of 2nd week of lead-in phase), and immediately after the intervention concluded (end of 4th week)

Eligibility
Key inclusion criteria
For inclusion into Constipation Group:

Adult with FC or IBS-C (18-65 years) with a BMI between 18 and 35kg/m2.

A1. The FC participants will be selected based on the following criteria:
Presence of FC according to Rome IV Diagnostic Criteria (fulfilled for the last three months with symptom onset at least six months prior to diagnosis):
1. Must include two or more of the following:
- Straining during more than 25% of defecations
- Lumpy or hard stools during more than 25% of defecations
- Sensation of incomplete evacuation for more than 25% of defecations
- Sensation of anorectal obstructions/blockage for more than 25% of defecations
- Manual manoeuvres to facilitate more than 25% of defecations (e.g. digital evacuation, support of the pelvic floor)
- Fewer than three complete spontaneous bowel movements per week

2. Loose stools are rarely present without the use of laxatives
3. Insufficient criteria for irritable bowel syndrome

A2. The participants with mild IBS-C will be selected based on the following Rome IV Diagnostic Criteria (fulfilled for the last three months with symptom onset at least six months prior to diagnosis):
1. Recurrent abdominal pain, on average, at least one day per week in the last three months, associated with two or more of the following:
- Related to defecation
- Associated with a change in frequency of stool
- Associated with a change in form (appearance) of stool

2. More than 25% of bowel movements with Bristol Stool form types 1 or 2 and less than 25% of Bowel movements of types 6 or 7.


B. For inclusion into Healthy Control group:

Adult (18-65 years) with a BMI between 18 and 35kg/m2, not meeting inclusion criteria for Constipation Group and any exclusion criteria.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Inability to give informed consent
- Pregnancy, breastfeeding or planning a pregnancy in the three months post-selection (study time frame)
- Alarm features associated with bowel habits, such as recent changes in bowel habits (onset less than three months), rectal bleeding, sudden weight loss, occult blood in stool, anaemia, anal fissures, bleeding haemorrhoids, and family history of gastrointestinal cancer at a young age or Irritable Bowel Disease (IBD)
- Known significant gastrointestinal disorder and disease other than IBS-C, diverticulitis, coeliac disease, IBS-D or mixed IBS, or previous bowel resection.
- Known systemic disease that could influence the gut directly or through medication use (e.g. diabetes, opiate or NSAID use)
- Chronic disease such as cardiovascular, cancer, renal failure, previous gastrointestinal surgery other than cholecystectomy or appendectomy, neurological conditions such as multiple sclerosis, spinal cord injury, or stroke
- Fasting blood glucose equals to or more than 6.0 mmol/l
- Known kiwifruit or latex allergy
- Laxative use and inability or unwillingness to stop laxative use for the seven days before sample collections.
- An IBS Severity Index score of over 300.
- Indication of inability to comply with the study procedures

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
This study will compare the effect of the same intervention on two distinct participant cohorts: individuals with functional constipation and individuals with constipation-predominant IBS versus healthy individuals without gastric issues.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
All statistical analyses will be completed by researchers under guidance of an independent biostatistician. Statistical analyses will describe the relationship between the consumption of kiwifruit and the bowel habit parameters.
This study is conducted as a superiority trial. The Guidelines of the Committee for Proprietary Medicinal Products (CPMP) does require the use of “intention- to-treat” analysis.
Categorical variables will be applied to Chi-squared tests (or Fisher’s exact tests for small samples) while continuous variables will be applied to (parametric) t-tests and (non-parametric) Mann-Whitney/Kruskal –Wallis tests for symmetrically and asymmetrically distributed data, respectively.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
15/08/2022
Actual
16/09/2022
Date of last participant enrolment
Anticipated
14/12/2023
Actual
25/09/2023
Date of last data collection
Anticipated
14/02/2024
Actual
16/11/2023
Sample size
Target
32
Accrual to date
Final
32
Recruitment outside Australia
Country [1] 24918 0
New Zealand
State/province [1] 24918 0
Auckland

Funding & Sponsors
Funding source category [1] 311912 0
Government body
Name [1] 311912 0
Ministry of Business Innovation and Employment
Country [1] 311912 0
New Zealand
Funding source category [2] 311913 0
Commercial sector/Industry
Name [2] 311913 0
Zespri International Limited
Country [2] 311913 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
University of Otago, Christchurch
2 Riccarton Avenue
Christchurch Central City
Christchurch
8011
Country
New Zealand
Secondary sponsor category [1] 313397 0
University
Name [1] 313397 0
Liggins Institute, University of Auckland
Address [1] 313397 0
85 Park Road,
Grafton, Auckland 1023
New Zealand
Country [1] 313397 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311348 0
Northern B Health and Disability Ethics Committees
Ethics committee address [1] 311348 0
Ethics committee country [1] 311348 0
New Zealand
Date submitted for ethics approval [1] 311348 0
Approval date [1] 311348 0
07/07/2022
Ethics approval number [1] 311348 0
21/NTB/96

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 120802 0
Prof Richard Mithen
Address 120802 0
Liggins Institute
University of Auckland
Private Bag 92019
Auckland 1142
Country 120802 0
New Zealand
Phone 120802 0
+64 99236691
Fax 120802 0
Email 120802 0
[email protected]
Contact person for public queries
Name 120803 0
Amber Milan
Address 120803 0
Liggins Institute
University of Auckland
Private Bag 92019
Auckland 1142
Country 120803 0
New Zealand
Phone 120803 0
+64 99234785
Fax 120803 0
Email 120803 0
[email protected]
Contact person for scientific queries
Name 120804 0
Amber Milan
Address 120804 0
Liggins Institute
University of Auckland
Private Bag 92019
Auckland 1142
Country 120804 0
New Zealand
Phone 120804 0
+64 99234785
Fax 120804 0
Email 120804 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual data is not available to the public. it would be a breach of data security.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
16728Informed consent form  [email protected]



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.