Clinical trial NCT02605148: TEFA Family Prevention: Glutenfree Diet to Preserve Beta-cell Function
Official title: TEFA TEDDY Family Prevention - Gluten Free Diet to Preserve Beta-cell Function in Subjects With Islet Autoimmunity.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Prediabetes
Type 1 Diabetes
Keywords: Islet autoimmunity
gluten free diet
prediabetes
prevention
type 1 diabetes
glucose tolerance test
Lead sponsor: Lund University
Sponsor class: OTHER
Collaborators: name: Juvenile Diabetes Research Foundation
First posted: 2015-11-16
Enrollment: 60
Sex: ALL
Minimum age (years): 2
Maximum age (years): 49
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

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Primary outcomes:
measure: Change in first phase insulin response (FPIR) from IvGTT
timeFrame: 24 months
measure: Change in area under the curve (AUC) C-peptide
timeFrame: 24 months
measure: Change in glucose metabolism
timeFrame: 24 months
Secondary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 24 months
Other outcomes:
Locations:
city: Malmö
country: Sweden
facility: Lund University, Department of Clinical Sciences Malmö
Study officials:
affiliation: Lund University
name: Maria Månsson Martinez, Nutricionist
role: PRINCIPAL_INVESTIGATOR
References:
citation: Martinez MM, Spiliopoulos L, Salami F, Agardh D, Toppari J, Lernmark A, Kero J, Veijola R, Tossavainen P, Palmu S, Lundgren M, Borg H, Katsarou A, Larsson HE, Knip M, Maziarz M, Torn C; and the TEDDY-Family (TEFA) Study Group. Heterogeneity of beta-cell function in subjects with multiple islet autoantibodies in the TEDDY family prevention study - TEFA. Clin Diabetes Endocrinol. 2022 Jan 5;7(1):23. doi: 10.1186/s40842-021-00135-6.
citation: Martinez MM, Salami F, Larsson HE, Toppari J, Lernmark A, Kero J, Veijola R, Koskenniemi JJ, Tossavainen P, Lundgren M, Borg H, Katsarou A, Maziarz M, Torn C; TEDDY Family (TEFA) Study Group. Beta cell function in participants with single or multiple islet autoantibodies at baseline in the TEDDY Family Prevention Study: TEFA. Endocrinol Diabetes Metab. 2020 Nov 5;4(2):e00198. doi: 10.1002/edm2.198. eCollection 2021 Apr.