Gluten and Amylase Trypsin Inhibitors (ATI) Free Diet

Study Overview
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Brief Summary
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Siblings of those with type 1 diabetes are at an increased risk of developing the disease themselves. Through prior research, the investigators have found that siblings as well as those with type 1 diabetes have a general level of inflammation in the body. The investigators are examining the role that diet plays in this level of inflammation by asking siblings of children with type 1 diabetes to go on a gluten and Amylase Trypsin Inhibitors (ATI)-free diet for 4 weeks. Blood and stool samples will be measured before the diet, after the diet is completed and again 4 weeks after participants resume their normal diet.

Official Title
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Gluten and Amylase Trypsin Inhibitors (ATI) as Nutritional Contributors to Type 1 Diabetes Susceptibility

Conditions
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Type1diabetes

Intervention / Treatment
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* Other: Gluten and Amylase Trypsin Inhibitors (ATI)-free diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females 2-23 years of age Full-sibling of an individual with a clinical diagnosis of type 1 diabetes Treatment naïve of any immunomodulatory agent Exclusion Criteria: Abnormal HbA1c, defined as ≥ 6% Previous or current use of a gluten-free diet Current diagnosis of celiac disease An elevated tissue transglutaminase IgA level (> 10 units/mL) Chronic (≥ 3 months duration) gastrointestinal disease or presence of gastrointestinal symptoms within the prior 6 weeks (e.g., abdominal pain, worsening constipation, diarrhea, or recurrent nausea +/- vomiting) Chronic inflammatory or autoimmune disease with the exception of well-controlled hypothyroidism or intermittent or mild persistent asthma not requiring the use of daily inhaled steroids Use of any medications that affect glucose metabolism (e.g., metformin) or the immune system (e.g., use of any glucocorticoids (inhaled, intranasal, oral, intravenous) within the previous 3 months) Use of any medications that could affect intestinal microbiota within the previous 3 months (e.g., antibiotics, prebiotics, or probiotics) Any condition that, in the investigator's opinion, may compromise study participation or may confound the interpretation of the study results

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 23 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: All subjects will receive a dietary intervention. They will be instructed and asked to follow a diet free of gluten and the protein amylase trypsin inhibitors (ATI), which is frequently found in gluten-containing foods, for four weeks. They will then be asked to resume their normal diet.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Dietary intervention<br>Participants will be asked to remove food containing gluten and ATI from their diets for 4 weeks. | Other: Gluten and Amylase Trypsin Inhibitors (ATI)-free diet<br>* Participants will be asked to avoid foods containing gluten and ATI (a similar protein found in grains) for 4 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the plasma-induced transcriptional assay | Investigators will measure the participants overall immune inflammation and regulation by a plasma-induced transcriptional bioassay. The change in this bioassay will be determined for each subject and the entire group both before and after the dietary intervention. This bioassay informs the investigators of which genes may be positively or negatively impacted by this dietary change and whether the removal of gluten and amylase trypsin inhibitors (ATI) affects a participant's immune state. | 2 years (study duration) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stool microbial composition | Stool samples will be collected both before and after the dietary intervention to determine if the removal of gluten and amylase trypsin inhibitors (ATI) from the diet affects the composition and density of the stool microbiota | 2 years (study duration) | 
| Plasma microbial antigen detection | Microbial antigen levels in the plasma of participants will be assayed both before and after the dietary intervention. Systemic microbial antigens are a marker of intestinal permeability so this measure will tell the investigators if the removal of gluten and amylase trypsin inhibitors (ATI) affects the degree of intestinal permeability/leakiness. | 2 years (study duration) | 
| Leukocyte analyses | The degree of responsiveness of participants leukocytes to stimulation with gluten and amylase trypsin inhibitors (ATI) will be measured in vitro both before and after the dietary intervention. | 2 years (study duration) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Siblings