ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12614000500651

Ethics application status

Approved

Date submitted

16/04/2014

Date registered

12/05/2014

Date last updated

13/09/2018

Type of registration

Prospectively registered

Titles & IDs

Public title

Identifying deficient colonic bacterial fermentation in patients with ulcerative colitis in remission

Scientific title

Colonic bacterial fermentation profiles in patients with Ulcerative Colitis (UC) following high vs low indigestible carbohydrate diets: biomarkers and implications for future therapies

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

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

Ulcerative colitis

Condition category

Condition code

Oral and Gastrointestinal

Inflammatory bowel disease

Diet and Nutrition

Other diet and nutrition disorders

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Individuals with ulcerative colitis in remission will be supplied with two diets differing in high or low amounts of indigestible carbohydrates over a 12-hour period. The diets will consist of only two meals, an evening meal the night before and a breakfast meal the morning of ingesting the pH-motility device. The evening meal will comprise of legumes, grains and starchy vegetables varying in indigestible carbohydrates whereas the breakfast meal will consist of a muesli bar. The HIGH arm will contain 10g fermentable carbohydrate per meal.

Compliance to the study diets will be assessed by food diaries, return of food containers and breath hydrogen tests. For the rest of the study period, participants will be following their usual diets.

Following the first dietary arm, there will be a 3-day washout period before participants cross over to the other study diet.

Intervention code [1]

Treatment: Other

Comparator / control treatment

The control diet will be the low indigestible carbohydrate diet and as mentioned in the intervention description, will be provided in 2 meals over a 12-hour period prior to ingesting the pH-motility device. The indigestible carbohydrate content in the LOW indigestible carbohydrate arm will be <2g per meal.

Control group

Dose comparison

Outcomes

Primary outcome [1]

The amount of fibre that is utilised or fermented (broken down by bacteria) in the large bowel will be analysed by measuring the stool content of starch and non-starch polysaccharides (NSP).

Timepoint [1]

The primary outcome will only be measured at baseline (prior to administering the interventional diets) and then used to categorise the subjects into good fibre utilisers or poor fibre utilisers for comparisons with the secondary outcomes.

Secondary outcome [1]

Intraluminal pH profiles of the large intestine will be calculated over time using a wireless pH-motility device that records pH data as it travels from the right to the left side of the colon.

Timepoint [1]

Gastrointestinal pH will be measured in the time period following ingestion of the morning meal on the first dietary arm until the device is passed from the gastrointestinal tract and then again 3 days later, after ingesting the morning meal of the 2nd dietary arm.

Secondary outcome [2]

The passage rate of fibre through the large intestine will also be measured by the wireless pH-motility device.

Timepoint [2]

Passage rate of fibre through the colon will be measured from the time period immediately following ingestion of the morning meal on the first dietary arm until the device is passed from the gastrointestinal tract and then again 3 days later, during the 2nd dietary arm.

Eligibility

Key inclusion criteria

(1) Individuals with ulcerative colitis in remission
- on stable medical or drug therapy for > 1 month

OR

(2) Healthy volunteers

Both groups must be aged 18-75 years old and have not taken any antibiotics in preceding 3 months

Minimum age

18 Years

Maximum age

75 Years

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

- Individuals with Crohn's disease, indeterminate colitis or have undergone surgical removal of partial or all of the colon
or
- individuals taking topical rectal therapies in preceding three months
or
- those taking medications affecting bowel function in preceding four weeks
or
- women who are pregnant or 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)

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

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Crossover

Other design features

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

1/06/2014

Actual

10/09/2014

Date of last participant enrolment

Anticipated

12/12/2016

Actual

14/11/2016

Date of last data collection

Anticipated

22/12/2016

Actual

1/12/2016

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

The Alfred - Prahran

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Ferring Pharmaceuticals

Address [1]

PO BOX 135, Pymble NSW 2073

Country [1]

Australia

Primary sponsor type

University

Name

Monash University

Address

Department of Gastroenterology, Central Clinical School, Monash University
The Alfred Centre
Level 6, 99 Commercial Rd,
Prahran 3004 VIC

Country

Australia

Secondary sponsor category [1]

Hospital

Name [1]

Department of Gastroenterology, The Alfred Hospital

Address [1]

Level 1, The Alfred, 99 Commercial Rd, Prahran 3004 VIC

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Alfred Human Research Ethics Committee

Ethics committee address [1]

Ethics and Research Governance Office
Ground Floor, Linay Pavilion
55 Commercial Rd, Melbourne VIC 3004

OR 
Ethics and Research Governance Office
The Alfred 
PO Box 315
Prahran VIC 3181

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

03/04/2014

Approval date [1]

06/06/2014

Ethics approval number [1]

121/14

Ethics committee name [2]

Monash University Human Research Ethics Committee (MUHREC)

Ethics committee address [2]

Monash University Clayton

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

27/06/2014

Approval date [2]

15/07/2014

Ethics approval number [2]

CF14/2107 - 20140001086

Summary

Brief summary

Ulcerative colitis (UC) is a chronic and relapsing inflammatory bowel disease (IBD) characterised by inflammation in the lining of the large bowel. Recent studies of the bacterial populations that normally reside in the large bowel (gut microbiota) have shown abnormalities (i.e., dysbiosis) in the faeces of patients with UC. Our research group has found evidence that the ability of the gut microbiota to ferment carbohydrates may be markedly defective and this cannot be corrected by simply providing more dietary fibre. Such fermentation is an important function of the microbiota as it delivers breakdown products that include short-chain fatty acids such as butyrate to the lining cells of the colon. Butyrate is the major source of nutrition for those cells and also has anti-inflammatory and anti-tumour-producing effects. This observation has potentially large implications for how we manage UC. If it is true, then manipulation of the bacteria and of the specific carbohydrate substrates they see by, for example, dietary manipulation of the types of carbohydrates they eat might have therapeutic benefit. Furthermore, such fermentation lowers acidity (pH) in the bowel and this lowering is utilised for the activation of some drugs commonly used in UC (e.g. mesalazine). Defective fermentation might lead to poor activation of those drugs and lack of effectiveness.

The major problem with studying fermentation in the large bowel is that most occurs in the proximal part of the large bowel – i.e., the part furthest away from the anus - and we have only been able to study it indirectly. Using swallowed capsule technology that transmits information to a transmitter worn by the patient (as used by the ‘pill-camera’), a new wireless pH-motility device, has been developed. This device is able to capture measurements for transit (speed of passage through the gut) and pH in real time and in a non-invasive manner as it travels along the entire gut. It is the pH measurement that provides our first way of examining fermentation in the intact colon.

We propose to measure the pH profiles in the gut of 10 healthy volunteers and of 20 patients with UC who do not have active disease after both a large and a minimal load of indigestible, fermentable carbohydrates. This will be achieved by controlled food intake over the 12 hours prior to the capsule being swallowed. This will give us a range of pH profiles related to high and low levels of fermentation in the gut. We will then be able to determine if the fermentation capability of patients with UC is truly deficient. The pH-motility device will also permit us to examine transit through the regions of the gut and provide mechanistic information on the role of gut transit in any abnormalities found. We anticipate variation in responses of patients (but not in healthy volunteers). In order to be able to identify patients with abnormal fermentation, we will also collect, prior to the investigations with a wireless pH-motility device, dietary intake information and faeces to determine if these indices provide the correlations with the pH profile.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Peter Gibson

Address

Department of Gastroenterology, Central Clinical School
Level 6 The Alfred Centre
99 Commercial Rd
Prahran 3004 VIC

Country

Australia

Phone

+61399030271

Fax

peter.gibson@monash.edu

Contact person for public queries

Name

CK Yao

Address

Department of Gastroenterology, Central Clinical School
Level 6 The Alfred Centre
99 Commercial Rd
Prahran 3004 VIC

Country

Australia

Phone

+61399030270

Fax

chu.yao@monash.edu

Contact person for scientific queries

Name

CK Yao

Address

Department of Gastroenterology, Central Clinical School
Level 6 The Alfred Centre
99 Commercial Rd
Prahran 3004 VIC

Country

Australia

Phone

+61399030270

Fax

chu.yao@monash.edu

No information has been provided regarding IPD availability

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

Source	Title	Year of Publication	DOI
Embase	Effects of fiber intake on intestinal pH, transit, and predicted oral mesalamine delivery in patients with ulcerative colitis.	2021	https://dx.doi.org/10.1111/jgh.15311

N.B. These documents automatically identified may not have been verified by the study sponsor.

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