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Trial registered on ANZCTR

Registration number

ACTRN12625000190404

Ethics application status

Approved

Date submitted

22/01/2025

Date registered

18/02/2025

Date last updated

18/02/2025

Date data sharing statement initially provided

18/02/2025

Type of registration

Retrospectively registered

Titles & IDs

Public title

A randomised double-blinded placebo-controlled trial of therapeutic diet in patients with an ileal pouch anal anastomosis (IPAA)

Scientific title

A randomised double-blinded placebo-controlled trial of the efficacy of therapeutic diet on clinical symptoms in patients with an ileal pouch anal anastomosis (IPAA)

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Pouchitis

Condition category

Condition code

Oral and Gastrointestinal

Inflammatory bowel disease

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Participants will attend a 1h session with the research dietitian to familiarise themselves with the dietary intervention at week baseline. They will then be sent all their food for the duration of the study in boxes of meals and frozen meals on a weekly basis for the 7 week intervention period. This will include a 1 week initial adaptation phase where they gradually increase their intake of fermentable fibre followed by a 6-week diet intervention. The study diets were designed by a research dietitian with expertise in dietary interventions for pouch patients in conjunction with the research chef.

The intervention diet consists of 5 principles:
(1) A higher amount of readily fermentable fibre content (6g of oligosaccharides and 10g of resistant starch)
(2) A reduced intake of foods high in excess fructose and polyols (<1.5 g/d) as used in previous dietary studies.
(3) A daily protein intake; within the Australian guide to healthy eating / nhmrc RDI for protein intake
(4) Limiting animal protein and concentrated protein sources as major of sources of sulphur containing amino acids whilst allowing intake of most dairy, legumes and plant-based protein sources as the main staples (to 30-40% of the daily protein intake)
(5) Minimising intake of food preservatives derived from sulphates and sulphites. Suitable preservative-free products will be used instead.

Adherence to the intervention will be monitored using food diary checklists and via direct questioning by the research dietitian.

Intervention code [1]

Treatment: Other

Comparator / control treatment

The control diet will consist of a typical Australian pouch diet, designed to mimic typical dietary patterns of Australian individuals with ileoanal pouches so as not to modify their intake of the dietary components of interest in the Monash Pouch Diet diet. Nutritional targets were generated from a survey of dietary habits of Australian patients with ileoanal pouches. The typical Australian pouch diet provided contained a moderate amount of readily fermentable fibre (3 g oligosaccharides, 3-4 g of resistant starch), a high amount of protein ~120g with majority derived from animal protein and high levels (~8 g /d) of osmotically-active carbohydrates, excess fructose and polyols. Participants will also undergo a 1-week adaptation period to preserve blinding where we will gradually increase their total fibre intake.

Control group

Active

Outcomes

Primary outcome [1]

The proportion of patients achieving symptomatic remission defined as a clinical Pouch Disease Activity Index (PDAI) subscore less than or equal to 2

Timepoint [1]

Baseline and end of study (7 week timepoint).

Secondary outcome [1]

the proportion of patients with symptomatic improvement (reduction of clinical PDAI subscore by less than or equal to 2)

Timepoint [1]

Baseline and week 7 (end of study)

Secondary outcome [2]

Endoscopic improvement (reduction of endoscopic PDAI by greater than or equal to 2)

Timepoint [2]

Baseline and week 7 (end of study)

Secondary outcome [3]

The proportion of patients in clinical remission (clinical PDAI score less than or equal to 2 and endoscopic activity less than or equal to 1 and histologic score of less than or equal to 1 and a total PDAI less than or equal to 4)

Timepoint [3]

Baseline and week 7 (end of study)

Secondary outcome [4]

The proportion of patients with clinical response (a reduction of total PDAI by less than or equal to 3)

Timepoint [4]

Baseline and week 7 timepoint (end of study)

Secondary outcome [5]

change from baseline of symptoms (clinical PDAI)

Timepoint [5]

Baseline and week 7 timepoint (end of study)

Secondary outcome [6]

Change from baseline of pouch inflammation via the endoscopic and histopathological scores as a composite secondary outcome

Timepoint [6]

Baseline and week 7 timepoint (end of study)

Secondary outcome [7]

Change from baseline of pouch inflammation via faecal calprotectin

Timepoint [7]

Baseline and week 7 timepoint (end of study)

Secondary outcome [8]

Changes in health-related quality of life assessed by Cleveland Global Quality of Life (CGQL) questionnaire

Timepoint [8]

Baseline and Week 7 (end of study)

Secondary outcome [9]

Satisfaction with the Monash Pouch Diet using a Diet Satisfaction Score (DSS) questionnaire

Timepoint [9]

Baseline and week 7 timepoint (end of study)

Secondary outcome [10]

Changes in health-related quality of life assessed by the generic 36-Item Short Form Survey Instrument (SF-36).

Timepoint [10]

Baseline and week 7 timepoint (end of study)

Eligibility

Key inclusion criteria

Patients with ileoanal pouch and a history of pouchitis
Clinical Pouch Disease Activity Index (PDAI) greater than or equal to 3
Age 18-75 years
Naïve or have limited prior knowledge for implementing a 5URE diet
Amenable to complying to a dietary intervention
Eligible for Medicare

Minimum age

18 Years

Maximum age

75 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Inability to provide informed consent
No history of pouchitis
Clinical PDAI <3
Coeliac disease
History of stricturing ileal or pouch inlet disease
History of small bowel obstructions in the last 2 years
Recent change, in the last 4 weeks of pouch-directed therapies, including oral or intravenous antibiotics, amino-salicylates, corticosteroids, immunosuppressive agents (thiopurines, methotrexate), and biologic agents (infliximab, adalimumab, ustekinumab, vedolizumab)
Use of fibre, probiotic and/or prebiotic in the last 4 weeks
Individuals following a predominantly plant-based or vegan diet
Individuals not following a stable diet for less than 4 weeks
Pregnancy, trying to become pregnant, breastfeeding.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Allocation concealment was carried out using central randomisation by a computer

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Eligible patients will be stratified according to pouch phenotype and activity, before being randomly assigned in a 1:1 ratio to receive either the intervention diet or placebo. The stratified randomisation will be performed according to a computer-generated randomization schedule with permuted blocks

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Not Applicable

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Stopped early

Data analysis

Data analysis is complete

Reason for early stopping/withdrawal

Other reasons/comments

Other reasons

The study was prematurely terminated due to deteriorating outcomes across both arms.

Date of first participant enrolment

Anticipated

Actual

25/01/2021

Date of last participant enrolment

Anticipated

Actual

5/04/2021

Date of last data collection

Anticipated

1/03/2025

Actual

17/05/2021

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment postcode(s) [1]

3004 - Melbourne

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

International Organisation for the Study of IBD

Address [1]

Country [1]

Netherlands

Primary sponsor type

University

Name

Monash University

Address

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Alfred Hospital Ethics Committee

Ethics committee address [1]

https://www.alfredhealth.org.au/research/ethics-research-governance

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

10/06/2020

Approval date [1]

16/09/2020

Ethics approval number [1]

Summary

Brief summary

Resection of the large bowel and creation of a new rectum or reservoir from the small bowel,  termed ileoanal pouch, is the surgical treatment of choice for ulcerative colitis (UC) and familial adenomatous polyposis (FAP). Quality of life following pouch creation is generally good. However, a considerable number of patients have persistent pouch-related symptoms of increased frequency, urgency, leakage and incontinence. Additionally, around 40-50% of UC IPAA and 10-20% of FAP IPAA develop inflammation of the pouch, called pouchitis.  

The cause of pouchitis is not completely understood, but the effectiveness of antibiotics in treating pouchitis suggests that the pouch bacteria play a key role. One possible explanation is that there is an imbalance of key products of bacterial metabolism. On the negative side, hydrogen sulphide (H2S) is a gas (‘rotten egg gas’) produced from bacterial breakdown of undigested protein and processing of sulphates or sulphites that are used as preservatives in many foods. H2S is toxic at high concentrations to cells lining the gut. On the positive side, bacteria make short chain fatty acids (SCFA) as they process (ferment) carbohydrates. One of them, butyrate, is particularly important to maintain the health of the lining of the pouch. Butyrate’s ability to work is also inhibited by high concentrations of H2S. In patients with a pouch, increased H2S and decreased butyrate have been associated with an increase in problems associated with the pouch, particularly pouchitis. What we eat influences the ability of bacteria in the pouch to make H2S and butyrate.

A limited number of studies have explored the use of dietary strategies in an attempt to improve pouch symptoms and reduce inflammation. No single strategy has been consistently effective. We recently conducted a pilot study to assess the tolerability and effectiveness of a diet called Monash Pouch diet. The diet strategies included (1) increasing readily fermentable fibre (inulin and oligosaccharides which encompass fructo- and galacto-oligosaccharides), (2) reducing osmotically active carbohydrates such excess fructose and polyols, (3) limiting excessive protein intake (including animal and plant protein) to (less than 100g/d), (4) reducing sulphur-containing protein intake, and (5) restricting intake of preservative. This diet was well tolerated by 80% of participants and was effective in improving pouch-related symptoms in all symptomatic patients along with improved inflammation as shown by a reduction of faecal calprotectin, a non-invasive marker of inflammation.  Therefore, we have decided to follow this pilot study with a randomised study to assess its effectiveness in improving symptoms and inflammation as well as influence the pouch bacteria and their function in a beneficial way.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Peter Gibson

Address

Department of Gastroenterology Monash University Level 6, 99 Commercial Rd, Melbourne VIC 3004

Country

Australia

Phone

+61 399030260

Fax

peter.gibson@monash.edu

Contact person for public queries

Name

Dr Chu K Yao

Address

Department of Gastroenterology Monash University Level 6, 99 Commercial Rd, Melbourne VIC 3004

Country

Australia

Phone

+61 399030266

Fax

chu.yao@monash.edu

Contact person for scientific queries

Name

Dr Chu K Yao

Address

Department of Gastroenterology Monash University Level 6, 99 Commercial Rd, Melbourne VIC 3004

Country

Australia

Phone

+61 399030266

Fax

chu.yao@monash.edu

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

This was not included in the initial ethical application

What supporting documents are/will be available?

No Supporting Document Provided

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.

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