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Trial registered on ANZCTR


Registration number
ACTRN12624000708550
Ethics application status
Approved
Date submitted
27/03/2024
Date registered
6/06/2024
Date last updated
6/06/2024
Date data sharing statement initially provided
6/06/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Understanding how gluten causes symptoms in coeliac disease (CD)
and non-coeliac gluten sensitivity (NCGS)
Scientific title
Uncovering the cellular, cytokine and hormone pathway between gluten immunity and adverse symptoms in coeliac disease and gluten sensitivity to define novel treatments and identify symptom biomarkers following single dose gluten challenge.
Secondary ID [1] 311819 0
Nil known
Universal Trial Number (UTN)
U1111-1306-0949
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Coeliac Disease
 333347 0
Non-Coeliac Gluten Sensitivity 333348 0
Condition category
Condition code
Oral and Gastrointestinal 330027 330027 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 330028 330028 0 0
Other inflammatory or immune system disorders
Inflammatory and Immune System 330029 330029 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a single-blind, placebo-controlled cross-over gluten challenge study to assess symptoms and symptom biomarkers in the blood and small intestine after ingestion of gluten or placebo in patients with coeliac disease (CD), non-coeliac gluten sensitivity (NCGS) and unaffected controls.

3 grams of gluten protein or matched placebo will be administered via oral capsules. Exact dose will be fixed for all patients and allocation (gluten or placebo) will not be revealed to the participant. Each participant will undertake two single-dose challenges with a minimum 4-week wash-out period between interventions (one placebo, one gluten). Gluten and placebo will both be food-grade. This will be administered and supervised by a Clinical Coordinator and/or Gastroenterologist.

Assessments may include: blood collection and gastroscopy with duodenal biopsies before and within 6 hours after gluten/placebo challenge and hourly symptom monitoring using a patient-reported outcome measure.

Recruitment, blood collection and gluten challenges will be undertaken at the Clinical Translation Centre, Walter and Eliza Hall Institute (CTC WEHI) or Clinical Translation Centre at the Royal Melbourne Hospital (CTC RMH). Gastroscopies will be performed in the Royal Melbourne Hospital (RMH).
Intervention code [1] 328274 0
Diagnosis / Prognosis
Comparator / control treatment
Each participant will undergo both gluten and placebo challenges with a washout period in between. Placebo capsules will contain commercially available food grade rice flour.

An additional comparator will be the measured differences between CD, NCGS and unaffected control participants.
Control group
Placebo

Outcomes
Primary outcome [1] 337789 0
Peak circulating serotonin (5-HT)
Timepoint [1] 337789 0
Baseline, plus 2, 4 and 6 hours post-challenge
Secondary outcome [1] 433331 0
Duodenal tissue IL-2 gene expression
Timepoint [1] 433331 0
From duodenal biopsy tissue collected 4 hours post-gluten or -placebo challenge
Secondary outcome [2] 433332 0
Symptoms will be measured as a composite outcome using a modified Coeliac Disease Patient Reported Outcome measure (CeD PRO) that will include assessment of abdominal cramping/pain, bloating, constipation, diarrhoea, gas, loose stools, nausea, vomiting, headaches and tiredness.
Timepoint [2] 433332 0
Within one hour before gluten/placebo challenge and again hourly up to 6 hours post-challenge.

Eligibility
Key inclusion criteria
1. Adults 18 to 75 years of age (inclusive) who have signed an informed consent form.
2. The coeliac cohort will have CD diagnosed on the basis of duodenal biopsies showing villous atrophy and abnormal CD-specific serology
3. The NCGS cohort will have CD excluded on the basis of duodenal biopsies showing no villous atrophy and/or normal CD-specific serology whilst eating gluten, or negative HLA susceptibility for CD
4. The unaffected (healthy) controls will have normal CD-specific serology whilst eating gluten and no reported gluten-specific symptoms.
5. Have followed a GFD prior to participation for the required length of time
6. Willingness to consume up to 6 grams of vital wheat gluten
7. Willingness to undergo study procedures.
8. Able to read and understand English
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Intentional consumption of gluten-containing food within the previous one month in the CD and NCGS groups.
2. Any medical condition or an immune-suppressing medical treatment taken within the previous 3 months that in the opinion of the investigator would impact the immune response (other than CD), confound interpretation of study results, or pose an increased risk to the patient. Topical or inhaled corticosteroids are acceptable.
3. Females who are pregnant, including those with positive urinary pregnancy test on the first day of screening

Study design
Purpose of the study
Diagnosis
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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/07/2024
Actual
Date of last participant enrolment
Anticipated
1/05/2027
Actual
Date of last data collection
Anticipated
1/07/2027
Actual
Sample size
Target
80
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 26322 0
Royal Melbourne Hospital - Royal Park campus - Parkville
Recruitment postcode(s) [1] 42296 0
3052 - Parkville

Funding & Sponsors
Funding source category [1] 316155 0
Government body
Name [1] 316155 0
NHMRC Ideas Grant App 2012225
Country [1] 316155 0
Australia
Primary sponsor type
Other
Name
Walter and Eliza Hall Institute
Address
Country
Australia
Secondary sponsor category [1] 318344 0
Hospital
Name [1] 318344 0
Royal Melbourne Hospital
Address [1] 318344 0
Country [1] 318344 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314984 0
The Royal Melbourne Hospital Human Research Ethics Committee
Ethics committee address [1] 314984 0
https://www.thermh.org.au/research/researchers/ethics
Ethics committee country [1] 314984 0
Australia
Date submitted for ethics approval [1] 314984 0
27/04/2022
Approval date [1] 314984 0
22/08/2022
Ethics approval number [1] 314984 0
2022.136

Summary
Brief summary
Coeliac disease and gluten sensitivity are common illnesses that are associated with unpleasant symptoms caused by the consumption of gluten. These symptoms can greatly impair a sufferer’s quality of life. How gluten causes symptoms is poorly understood. This study aims to understand the bodily processes that are important in the development of symptoms to gluten. This information will be important for the development of treatments that can prevent or treat gluten-induced symptoms. We aim to identify markers in the blood that can be used by doctors to help in the diagnosis of gluten sensitivity and also for monitoring the effect of new treatments for coeliac disease.
Trial website
Trial related presentations / publications
Public notes
Gluten/placebo challenge and gastroscopy procedures may be postponed or cancelled if participants have symptoms of fever, cough, shortness of breath, or suspicion of COVID-19 infection.

Contacts
Principal investigator
Name 133322 0
A/Prof Jason Tye-Din
Address 133322 0
Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, VIC 3057
Country 133322 0
Australia
Phone 133322 0
+61 3 9345 2533
Fax 133322 0
Email 133322 0
[email protected]
Contact person for public queries
Name 133323 0
Lee Henneken
Address 133323 0
Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, VIC 3057
Country 133323 0
Australia
Phone 133323 0
+61 3 9345 2883
Fax 133323 0
Email 133323 0
[email protected]
Contact person for scientific queries
Name 133324 0
Jason Tye-Din
Address 133324 0
Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, VIC 3057
Country 133324 0
Australia
Phone 133324 0
+61 3 9345 2533
Fax 133324 0
Email 133324 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


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.