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

Not Applicable

• Conditions: Prediabetes; Type 1 Diabetes
• Interventions: Dietary Supplement: Gluten free diet; Dietary Supplement: Vitamin D; Dietary Supplement: Omega 3 fatty acid; Dietary Supplement: Probiotics

• Registration Number: NCT02605148
• Lead Sponsor: Lund University

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2015-11-11
• Study First Submitted QC: 2015-11-13
• Study First Posted: 2015-11-16
• Study Start: 2015-12
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-18
• Last Update Posted: 2021-10-26
• Primary Completion: 2022-12
• Study Completion: 2022-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Subjects from two (2) to 49,99 years of age.
2. 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.
3. 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

1. Ongoing treatment with immunosuppressant therapy (topical or inhaled steroids are accepted).

2. Diabetes.

3. Treatment with any oral or injected anti-diabetic medications.

4. Significantly abnormal hematology results at screening.

5. Participation in other clinical trials with a new chemical entity within the previous 3 months.

6. History of hypercalcemia.

7. Presence of associated serious disease or condition.

8. Diabetes-protective HLA-DQ6-allele.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Normal diet	Vitamin D	Normal diet. Vitamin D 800 U Daily, Omega 3 fatty acids and probiotics as nutritional supplements.
Gluten free diet	Gluten free diet	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.
Gluten free diet	Probiotics	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.
Gluten free diet	Omega 3 fatty acid	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.
Normal diet	Omega 3 fatty acid	Normal diet. Vitamin D 800 U Daily, Omega 3 fatty acids and probiotics as nutritional supplements.
Gluten free diet	Vitamin D	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.
Normal diet	Probiotics	Normal diet. Vitamin D 800 U Daily, Omega 3 fatty acids and probiotics as nutritional supplements.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events	24 months	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.

Trial Locations

Locations (1)

Lund University, Department of Clinical Sciences Malmö; 🇸🇪 Malmö, Sweden