Clinical trial NCT05585983: INfluenza VaccInation To Mitigate typE 1 Diabetes
Official title: INfluenza VaccInation To Mitigate typE 1 Diabetes (INVITED Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 1
Lead sponsor: Aarhus University Hospital
Sponsor class: OTHER
First posted: 2022-10-19
Enrollment: 100
Sex: ALL
Minimum age (years): 7
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In this double blind, placebo-controlled clinical trial participants are allocated to either influanza vaccination (active) or to placebo (control).
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in fasting residual β cell (C-peptide) function.
timeFrame: 12 months
Secondary outcomes:
measure: Change in fasting residual β cell (C-peptide) function.
timeFrame: 6 months.
measure: Change in HbA1c
timeFrame: 12 months.
measure: Change in insulin requirements.
timeFrame: 12 months.
measure: Time-In-Range of blood glucose.
timeFrame: 12 months.
measure: Variation of blood glucose.
timeFrame: 12 months.
Other outcomes:
measure: Proportion of participants with stimulated C-peptide >0.2 pmol/mL
timeFrame: 12 months
measure: HbA1c time in range
timeFrame: 12 months.
measure: Insulin Dose Adjusted A1c
timeFrame: 12 months
measure: Variation of blood glucose.
timeFrame: 6 months.
measure: Change in GAD 65 antibodies.
timeFrame: 12 months.
measure: Change in GAD 65 antibodies.
timeFrame: 6 months.
measure: Change in regulatory T cells.
timeFrame: 12 months.
measure: Change in insulin autoantibodies.
timeFrame: 12 months.
measure: Change in zinc transporter-8 autoantibodies
timeFrame: 12 months.
measure: Change in islet cell autoantibodies.
timeFrame: 12 months.
measure: Change in cytokine levels.
timeFrame: 12 months.
measure: Change in cytokine levels.
timeFrame: 6 months.
measure: Unplanned hospitalizations.
timeFrame: 12 months.
measure: Serum hemagglutinin inhibition antibody titers against the four viruses included in the vaccine
timeFrame: 12 months.
measure: Serum hemagglutinin inhibition antibody titers against the four viruses included in the vaccine
timeFrame: 6 months.
measure: Clnical endpoints.
timeFrame: Up to 5 years.
measure: Treatment-emergent hypoglycemic events (safety outcome)
timeFrame: Up to 12 months.
measure: Treatment-emergent events of diabetic ketoacidosis (safety outcome)
timeFrame: Up to 12 months.
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Steno Diabetes Center Copenhagen
city: Herning
country: Denmark
facility: Gødstrup Hospital
city: Holbæk
country: Denmark
facility: Holbaek Sygehus
city: Nykøbing Falster
country: Denmark
facility: Nykoebing F Sygehus
city: Randers
country: Denmark
facility: Randers Regional Hospital
city: Roskilde
country: Denmark
facility: Sjællands Universitetssygehus
city: Slagelse
country: Denmark
facility: Slagelse Hospital
city: Viborg
country: Denmark
facility: Viborg Regional Hospital
Study officials:
References: