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NCT Number: NCT05585983

INfluenza VaccInation To Mitigate typE 1 Diabetes

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.

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Key information

Conditions

Diabetes Mellitus, Type 1 Autoimmune Diseases Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Immune System Diseases Metabolic Diseases Nutritional and Metabolic Diseases

Age range

7 year–17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Aalborg University Hospital, Aalborg, Denmark

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Vaxigrip Tetra Sanofi Pasteur Europe

Biological

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.

Primary outcomes

  1. Change in fasting residual β cell (C-peptide) function.

    Time frame: 12 months

    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)

Secondary outcomes

  1. Change in fasting residual β cell (C-peptide) function.

    Time frame: 6 months.

    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)

  2. Change in HbA1c

    Time frame: 12 months.

    Measured as standard laboratory test in mmol/mol

  3. Change in insulin requirements.

    Time frame: 12 months.

    Measured as total insulin dose per kg body weight per day as a mean for the last 14 days.

  4. Time-In-Range of blood glucose.

    Time frame: 12 months.

    Defined as percentage time in range (3.9-10.0 mmol/L) of continuous glucose monitoring over 14 days.

  5. Variation of blood glucose.

    Time frame: 12 months.

    Determined as percent coefficient of variation of blood glucose over 14 days.

Other outcomes

  1. Proportion of participants with stimulated C-peptide >0.2 pmol/mL

    Time frame: 12 months

    Proportion of participants in each of the treatment groups with stimulated C-peptide >0.2 pmol/mL

  2. HbA1c time in range

    Time frame: 12 months.

    Defined as percentage time in range (48mmol/mol or below)

  3. Insulin Dose Adjusted A1c

    Time frame: 12 months

    Defined as: IDAA1c = HbA1c (%) +4*total daily insulin dose (IE/kg/24 h)

  4. Variation of blood glucose.

    Time frame: 6 months.

    Determined as percent coefficient of variation of blood glucose over 14 days.

  5. Change in GAD 65 antibodies.

    Time frame: 12 months.

    Laboratory method to be determined

  6. Change in GAD 65 antibodies.

    Time frame: 6 months.

    Laboratory method to be determined.

  7. Change in regulatory T cells.

    Time frame: 12 months.

    Defined as percentage change.

  8. Change in insulin autoantibodies.

    Time frame: 12 months.

    Laboratory method to be determined.

  9. Change in zinc transporter-8 autoantibodies

    Time frame: 12 months.

    Laboratory method to be determined.

  10. Change in islet cell autoantibodies.

    Time frame: 12 months.

    Laboratory method to be determined.

  11. Change in cytokine levels.

    Time frame: 12 months.

    Markers to be determined: IL2, IL6, IL8, IL10, TNFα. Laboratory method to be determined.

  12. Change in cytokine levels.

    Time frame: 6 months.

    Markers to be determined: IL2, IL6, IL8, IL10, TNFα. Laboratory method to be determined.

  13. Unplanned hospitalizations.

    Time frame: 12 months.

    Number of unplanned hospitalizations with reasons for hospitalizations.

  14. Serum hemagglutinin inhibition antibody titers against the four viruses included in the vaccine

    Time frame: 12 months.

    Antibody titers.

  15. Serum hemagglutinin inhibition antibody titers against the four viruses included in the vaccine

    Time frame: 6 months.

    Antibody titers.

  16. Clnical endpoints.

    Time frame: Up to 5 years.

    Hospitalizations and unplanned hospital contacts.

  17. Treatment-emergent hypoglycemic events (safety outcome)

    Time frame: Up to 12 months.

    Hypoglycemic events reported according to the American Diabetes Association classification

  18. Treatment-emergent events of diabetic ketoacidosis (safety outcome)

    Time frame: Up to 12 months.

    Events of diabetic ketoacidosis.

Study contacts

Contact information is provided by the study sponsor or research team.

Mads F. Kjølby, MD, PhD

CONTACT

[email protected]

004560866653

Ole Frøbert, MD, PhD

CONTACT

[email protected]

0046730895413

Sponsors and collaborators

Lead sponsor

Aarhus University Hospital

Other

Registry information

Official study title

INfluenza VaccInation To Mitigate typE 1 Diabetes (INVITED Trial)

Acronym: INVITED

Important dates

Study start
2022
Primary completion
2026
Study completion
2027
First posted
Oct 19, 2022
Registry last updated
May 22, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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