TEFA Family Prevention: Glutenfree Diet to Preserve Beta-cell Function

Study Overview
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Brief Summary
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To evaluate the effect of Gluten Free Diet (GFD) on beta-cell function and glucose metabolism in subjects with one or several islet autoantibodies without and with dysglycemia at baseline. Additionally, all subjects will be given treatment with Vitamin D, omega fatty acids and probiotics. Subjects will be randomized to GFD or normal diet during 18 months. Beta cell function will be evaluated at baseline, and during follow-up by glucose tolerance tests.

Detailed Description
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The design is a randomized controlled study to determine the safety and the effect of gluten free diet during 18 months on beta-cell function and glucose metabolism. Lead-in and nonstop supplement cocktail including vitamin D, omega fatty acids and probiotics will be used to equalize differences to reduce known confounders. All study subjects will meet with a dietician to obtain a 3-day diet record and to receive instructions on a healthy normal diet or GFD. Subjects (n=60) at 2-49.99 years of age positive for one or several islet autoantibodies will be recruited. Subjects with one islet autoantibody have done one or several oral glucose tolerance test (OGTT) prior to the baseline visit. One islet autoantibody positive subjects are only eligible if they have dysglycemia. All subjects will be randomized based on baseline intravenous glucose tolerance test (IvGTT) and OGTT into subjects without and with dysglycemia at baseline. Beta-cell function and glucose metabolism (alternating IvGTT and OGTT) will be assessed at baseline and after 6, 12, 18 months of treatment and after 6 months of wash out on a normal healthy diet. Adverse events and safety Adverse event will be obtained at visits and during the study, which will be monitored. It is expected that subjects with one or several islet autoantibodies will show a loss compared to baseline of beta-cell function and glucose control. GFD is expected to reduce the loss in subjects on a healthy diet.

Official Title
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TEFA TEDDY Family Prevention - Gluten Free Diet to Preserve Beta-cell Function in Subjects With Islet Autoimmunity.

Conditions
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Prediabetes, Type 1 Diabetes

Intervention / Treatment
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* Dietary Supplement: Gluten free diet
* Dietary Supplement: Omega 3 fatty acid
* Dietary Supplement: Vitamin D
* Dietary Supplement: Probiotics


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects from two (2) to 49,99 years of age. At least one type 1 diabetes-associated autoantibody (to glutamic acid (GADA), insulin (IAA), insulinoma-associated protein 2 (IA-2A) or zinktransporter 8 (ZnT8R/W/QA) in subjects with impaired glucose metabolism OR at least two type 1 diabetes-associated autoantibodies, regardless of normal or impaired glucose metabolism. Written informed consent from research subject. If a child, also from the child's parents or legal acceptable representative(s) according to local regulations. Exclusion Criteria: Ongoing treatment with immunosuppressant therapy (topical or inhaled steroids are accepted). Diabetes. Treatment with any oral or injected anti-diabetic medications. Significantly abnormal hematology results at screening. Participation in other clinical trials with a new chemical entity within the previous 3 months. History of hypercalcemia. Presence of associated serious disease or condition. Diabetes-protective HLA-DQ6-allele. -

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gluten free diet<br>Gluten free diet during 18 months. The subjects will be referred to a nutritionist every 6 months. Vitamin D 800 U Daily, Omega 3 fatty acids and probiotics as nutritional supplements. | Dietary Supplement: Gluten free diet<br>* Gluten free diet during 18 months.<br>Dietary Supplement: Omega 3 fatty acid<br>* Omega 3 fatty acid<br>Dietary Supplement: Vitamin D<br>* Vitamin D 800 U/day<br>Dietary Supplement: Probiotics<br>* Probiotics<br>|
| Active Comparator: Normal diet<br>Normal diet. Vitamin D 800 U Daily, Omega 3 fatty acids and probiotics as nutritional supplements. | Dietary Supplement: Omega 3 fatty acid<br>* Omega 3 fatty acid<br>Dietary Supplement: Vitamin D<br>* Vitamin D 800 U/day<br>Dietary Supplement: Probiotics<br>* Probiotics<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in first phase insulin response (FPIR) from IvGTT | Change in First phase insulin response from IvGTT during follow-up | 24 months | 
| Change in area under the curve (AUC) C-peptide | Change in AUC C-peptide from OGTT during follow-up | 24 months | 
| Change in glucose metabolism | Change from normal to impaired glucose metabolism during follow-up | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events | To evaluate safety of GFD compared to recommended normal diet in the placebo group in subjects supplemented with lead in and nonstop treatment with a cocktail including vitamin D, omega fatty acids and probiotics. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Islet autoimmunity, gluten free diet, prediabetes, prevention, type 1 diabetes, glucose tolerance test