INfluenza VaccInation To Mitigate typE 1 Diabetes

Diabetes Mellitus, Type 1 Clinical Trial

— INVITED  

Official title:

INfluenza VaccInation To Mitigate typE 1 Diabetes (INVITED Trial)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05585983
• Other study ID #: INVITED-2022
• Status: Recruiting
• Phase: Phase 4
• Start date: December 14, 2022
• Est. completion date: June 1, 2026

Study information

• Verified date: March 2024
• Source: Aarhus University Hospital
• Contact: Ole Frøbert, MD, PhD
• Phone: 0046730895413
• Email: olefro[@]clin.au.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: June 1, 2026
• Est. primary completion date: April 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1

Intervention

Biological:
• Vaxigrip Tetra Sanofi Pasteur Europe
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.

Locations

Country	Name	City	State
Denmark	Aalborg University Hospital	Aalborg
Denmark	Aarhus University Hospital	Aarhus
Denmark	Gødstrup Hospital	Herning
Denmark	Randers Regional Hospital	Randers
Denmark	Viborg Regional Hospital	Viborg

Sponsors (1)

Lead Sponsor	Collaborator
Aarhus University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Proportion of participants with stimulated C-peptide >0.2 pmol/mL	Proportion of participants in each of the treatment groups with stimulated C-peptide >0.2 pmol/mL	12 months
Other	HbA1c time in range	Defined as percentage time in range (48mmol/mol or below)	12 months.
Other	Insulin Dose Adjusted A1c	Defined as: IDAA1c = HbA1c (%) +4*total daily insulin dose (IE/kg/24 h)	12 months
Other	Variation of blood glucose.	Determined as percent coefficient of variation of blood glucose over 14 days.	6 months.
Other	Change in GAD 65 antibodies.	Laboratory method to be determined	12 months.
Other	Change in GAD 65 antibodies.	Laboratory method to be determined.	6 months.
Other	Change in regulatory T cells.	Defined as percentage change.	12 months.
Other	Change in insulin autoantibodies.	Laboratory method to be determined.	12 months.
Other	Change in zinc transporter-8 autoantibodies	Laboratory method to be determined.	12 months.
Other	Change in islet cell autoantibodies.	Laboratory method to be determined.	12 months.
Other	Change in cytokine levels.	Markers to be determined: IL2, IL6, IL8, IL10, TNFa. Laboratory method to be determined.	12 months.
Other	Change in cytokine levels.	Markers to be determined: IL2, IL6, IL8, IL10, TNFa. Laboratory method to be determined.	6 months.
Other	Unplanned hospitalizations.	Number of unplanned hospitalizations with reasons for hospitalizations.	12 months.
Other	Serum hemagglutinin inhibition antibody titers against the four viruses included in the vaccine	Antibody titers.	12 months.
Other	Serum hemagglutinin inhibition antibody titers against the four viruses included in the vaccine	Antibody titers.	6 months.
Other	Clnical endpoints.	Hospitalizations and unplanned hospital contacts.	Up to 5 years.
Other	Treatment-emergent hypoglycemic events (safety outcome)	Hypoglycemic events reported according to the American Diabetes Association classification	Up to 12 months.
Other	Treatment-emergent events of diabetic ketoacidosis (safety outcome)	Events of diabetic ketoacidosis.	Up to 12 months.
Primary	Change in fasting residual ß cell (C-peptide) function.	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)	12 months
Secondary	Change in fasting residual ß cell (C-peptide) function.	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)	6 months.
Secondary	Change in HbA1c	Measured as standard laboratory test in mmol/mol	12 months.
Secondary	Change in insulin requirements.	Measured as total insulin dose per kg body weight per day as a mean for the last 14 days.	12 months.
Secondary	Time-In-Range of blood glucose.	Defined as percentage time in range (3.9-10.0 mmol/L) of continuous glucose monitoring over 14 days.	12 months.
Secondary	Variation of blood glucose.	Determined as percent coefficient of variation of blood glucose over 14 days.	12 months.