Gluten Reduction and Risk of Celiac Disease (GRAIN)

January 22, 2024 updated by: Lund University

Gluten Reduction After Infancy and Risk of Celiac Disease

Celiac disease shares many features of other autoimmune diseases such as type 1 diabetes. Recently, it was published that higher amounts of gluten intake increased the risk for celiac disease. Optimal amounts of gluten to be introduced during weaning have not yet been established. The aim is to investigate if a gluten-restricted diet (e.g. below 3 gram per day) during the first 3 years of life will reduce the risk of develop CDA and IA in genetically predisposed children by the age of 7 years. Children who screened positive for HLA DQ2/X (X is neither DQ2 nor DQ8) in the GPPAD-02 (ASTR1D [ClinicalTrials.gov Identifier NCT03316261]) screening will be contacted by a study nurse.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Gluten is a complex mixture of proteins, mainly gliadin and glutenin, rich in proline and glutamine amino acids which make these proteins resistant to complete degradation by enzymes in the small intestinal. Intolerance to gluten leads to inflammation of the intestinal epithelium and villous atrophy, a disorder called celiac disease. Celiac disease shares many features of other autoimmune diseases such as type 1 diabetes (T1D). First, celiac disease is associated with certain HLA genotypes of whom 95% of all patients with celiac disease carry the haplotypes DQA1*0501-DQB1*0201 (abbreviated DQ2) and the reminder 5% DQA1*0301-DQB1*0302 (abbreviated DQ8). There is a gene dose effect of HLA-DQ on the risk of develop celiac disease; 20% of the children homozygous for HLA-DQ2/DQ2 will develop celiac disease by 10 years of age. Second, celiac disease is also strongly associated with the presence of autoantibodies directed against tissue transglutaminase (tTGA) that occurs in 100% of children with celiac disease. Timing of gluten introduction and breastfeeding duration have previously been proposed to influence risk for celiac disease. However, based on the results from the multinational birth cohort study The Environmental determinants of Diabetes in the Young (TEDDY) study and other observational studies, timing of gluten introduction seems not associated with celiac disease in genetically at-risk children. In an RCT, introduction of small amounts of gluten at the age of 4-6 months did not reduce the risk for celiac disease by the age of 3 years in genetically at-risk children. Current international infant feeding recommendations recommend that gluten is introduced into the infant's diet anytime between 4-12 months of age and that consumption of large quantities of gluten should be avoided during the first month after gluten introduction and during infancy. Recently, the TEDDY study published that higher amounts of gluten intake increased the risk for celiac disease, which have been confirmed in two other observational cohort studies. In the TEDDY study, daily gluten intake was associated with higher increased risk of developing persistently positive tTGA, a definition coined celiac disease autoimmunity (CDA), as well as with celiac disease for every 1-g/day increase in gluten intake. Optimal amounts of gluten to be introduced during weaning have not yet been established. It is well known that an overlap between celiac disease and T1D exists most likely due to shared genetic risks of HLA-DQ2 and/or DQ8 in both disorders. Prospective studies in infants genetically predisposed to T1D and celiac disease showed that antibody positivity to both disorders begins in the first 1-3 years of life. The study aim is to investigate if a gluten-restricted diet during the first 3 years of life will reduce the risk of develop CDA and IA in genetically predisposed children by the age of 7 years.

Study Type

Interventional

Enrollment (Estimated)

1000

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Sweden
      • Malmö, Sweden, 20502
        • Recruiting
        • Clinical Research Center (CRC), Bldng 60:11
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 months to 10 months (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • children screened positive for HLA DQ2/X (X is neither DQ2 or DQ8)
  • children who refused enrolment to the on-going study PreSiCe (ClinicalTrials.gov Identifier NCT03562221)

Exclusion Criteria:

  • congenital chronic disorder where intervention with diet may be affected
  • written informed consent from both caregivers are missing

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: No intervention
The group will be followed without any intervention, with regular visits at the research clinic.
Experimental: Gluten reduced diet

Subjects will follow a diet that does not exceed a daily intake of 3 gram gluten.

The group will be followed with regular visits at the research clinic.
Behavioral: Gluten reduced diet
Dietary advice focusing on reducing gluten intake in children

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Celiac disease autoimmunity (CDA)
Time Frame: from 6 months of age up until 7 years of age
Children tested positive for tissue transglutaminase autoantibodies (tTGA) in two consecutive serum samples 3-6 months apart.
from 6 months of age up until 7 years of age

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Celiac disease (CD)
Time Frame: from 6 months of age up until 7 years of age
celiac disease diagnosed, defined by intestinal biopsy showing a Marsh score of >2 or by high levels of tTGA with symptoms.
from 6 months of age up until 7 years of age

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Islet autoimmunity
Time Frame: from 6 months of age up until 7 years of age
Children tested positive for typ1 1 diabetes related autoantibodies (IAA, GADA, IA2A) in two consecutive serum samples 3-6 months apart.
from 6 months of age up until 7 years of age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lund University

Investigators

  • Principal Investigator: Daniel Agardh, MD, PhD, Lund University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 5, 2021

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2035

Study Registration Dates

First Submitted

October 13, 2020

First Submitted That Met QC Criteria

October 13, 2020

First Posted (Actual)

October 20, 2020

Study Record Updates

Last Update Posted (Estimated)

January 24, 2024

Last Update Submitted That Met QC Criteria

January 22, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2020-00446

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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