INfluenza VaccInation To Mitigate typE 1 Diabetes (INVITED)

In a multicenter, prospective, randomized, controlled clinical trial to compare influenza vaccination and placebo in sustaining β cell function in early type 1 diabetes mellitus.

Type 1 diabetes (T1D) is an autoimmune disease in which T cells attack and destroy the insulin-producing β cells in the pancreatic islets. In theory, immunotherapies aimed at re-programming the immune system to avoid β cell destruction is a promising strategy to prevent T1D or delay onset of overt disease. In this trial we test the hypothesis that influenza vaccination is superior to no influenza vaccination in sustaining β cell function in early T1D. Secondary outcome measures include change in autoantibodies directed against antigens present in the pancreatic islets, measures of severity of disease, change in inflammatory markers, and antibody titers against the four viruses included in the vaccine. Despite improvements in care, T1D is a leading cause of debilitating complications and early death globally. Children with residual β cell function are at lower risk for severe hypoglycemia, have better diabetes regulation, and have lower insulin requirements compared to children without residual β cell function. Thus, a simple, cheap treatment to mitigate T1D is highly warranted.

In this double blind, placebo-controlled clinical trial participants are allocated to either influanza vaccination (active) or to placebo (control).

The following are masked in the study: Participant, Care Provider, Investigator, Outcomes Assessor. The following are not masked: unblinded study nurses at participating sites randomizing participants in the eCRF system. The unblinded study nurses are not otherwise involved or participating in the study.

We will use 0.5 mL standard dose quadrivalent influenza vaccine containing 15 μg of hemagglutinin per strain consistent with WHO recommendations according to season.

Measured as the area under the concentration-time curve (AUC) for mixed-meal tolerance test-stimulated C-peptide concentration over 4 hours relative to baseline (AUC 0-4 h, C-peptide, 12 months/ AUC 0-4 h, C-peptide, baseline)

Measured as the area under the concentration-time curve (AUC) for mixed-meal tolerance test-stimulated C-peptide concentration over 4 hours relative to baseline (AUC 0-4 h, C-peptide, 6 months/ AUC 0-4 h, C-peptide, baseline)

Inclusion Criteria: Patients hospitalized with newly diagnosed type 1 diabetes mellitus. Written informed consent (parents, legal guardian). Exclusion Criteria: Influenza vaccination during the current influenza season. Strong indication for influenza vaccination for non-diabetic disease. Severe allergy to eggs or previous allergic reaction to influenza vaccine. Suspicion of febrile illness or acute, ongoing infection. Hypersensitivity to the active substances or ingredients of Vaxigrip Tetra or against any residues, such as eggs (ovalbumin or chicken proteins), neomycin, formaldehyde and octoxinol. Patients with endogenic or iatrogenic immunosuppression that may result in reduced immunization response. Inability to provide informed consent from a parent or legal guardian. Age <7 or ≥18 years. Previous randomization in the INVITED trial.