Trial ID: ISRCTN82491599
Other - Phase 4 - Recruiting
Background and study aims The incidence of type 1 diabetes (T1D) increased sharply during the COVID-19 pandemic. Islet autoantibodies in the blood are the first signs of a child developing T1D. Research has shown that early childhood infection with the SARS-CoV-2 virus more than doubles the risk of developing islet autoantibodies. This virus can enter and infect the islet cells of the pancreas, so it is plausible this may increase susceptibility. The main aim of this study is to investigate whether vaccination against COVID-19 at the age of 6 months is superior to placebo in preventing the development of islet autoantibodies in children at increased genetic risk of T1D. Who can participate? Patients aged between 3 and 4 months with a high genetic risk of developing T1D (identified from the currently running INGRID-2 trial) What does the study involve? Participants will receive vaccination with BioNTech/Pfizer Comirnaty 3 mcg in three doses between 6 and 11 months of age. Half of the recruited patients will receive the SARS-CoV-2 vaccine and half will receive placebo vaccination (normal saline). Ongoing monitoring visits will occur post-vaccination for 2-1/2 to 6 years, depending on when the participants is recruited into the study. Blood and stool samples will be collected at each visit and participants will collect weekly saliva samples and monthly stool samples at home for infection surveillance. They will also complete a fortnightly questionnaires for the first 24 months around infections and twice during the study around physical and mental health. What are the possible benefits and risks of participating? A potential benefit is the prevention or delay of developing islet autoantibodies and type 1 diabetes. Such a benefit can not be guaranteed, however, regular blood testing will help to detect and closely monitor the early stages of type 1 diabetes which can reduce the risk of complications. The vaccine that will be used in the study will be Comirnaty® Omicron XBB.1.5 or future variant developments replacing current Comirnaty vaccines, which is approved in the UK from 6 months of age. For primary vaccination it is given in three doses of 3 µg each; the first two doses are given 3 to 6 weeks apart, followed by a third dose given at least 8 weeks after the second dose. For children within these age groups, the vaccine is given as injections in the muscles of the thigh. The most common side effects (listed in SmPC as >1/1,000) in children aged from 6 months to 4 or 5 years were comparable to those seen in older age groups. Irritability, sleepiness, loss of appetite, rash, mild temperatures, diarrhoea and less commonly vomiting, lymphadenopathy and night sweats. Redness, swelling and tenderness at the injection site were also common side effects in children aged 6 to 23 months. These effects were usually mild or moderate and improved within a few days of vaccination. Rarer side effects (<1/1,000) are detailed in the SmPC for the vaccine. The researchers will ensure participants' families are aware of these potential side effects and will be given advice on how to minimise these. The blood samples taken as part of the trial involve risks such as slight pain or bruising at the injection site and occasional discomfort. This will be minimised as much as possible by using on-site staff who are skilled in paediatric phlebotomy and distraction techniques, as well as the use of anaesthetic cream/spray at the puncture site. The study involves a large number of procedures, especially up to age 2 years. These include frequent study visits and blood draws, up to weekly collection of saliva samples, monthly collection of stool samples and responding to questions fortnightly. This is considerably more than what is standard care during this age and may be burdensome for children and participating families. The extent of the procedures as compared to standard care will be explained during the consent process. In a previous study, which enrolled children from age 4 months for a similar study duration and blood draw schedule, the study drop-out rate was low (<10%). Therefore, the study procedures are considered tolerable to the majority of participants and families. The psychological questionnaire will monitor and identify families requiring attention due to participation demands and solutions to reduce the demands such as less frequent sampling or questionnaires will be discussed with these families. The researchers will try to ensure that all appointments are run as promptly and smoothly as possible to minimise time commitment. Children in the placebo group will be denied access to the benefits of a COVID-19 vaccine, including the possible prevention of serious early and late complications from a COVID-19 infection. The current number of children below the age of 5 years who are provided with this benefit through vaccination is extremely low (<0.1%). Further mitigation of the risk includes excluding children with diseases or treatments that lead to immune deficiency. This exclusion helps minimize the potential risk for this specific group of participants. In the UK, COVID-19 vaccination for children this age is only advised for those in a clinical risk group, so participation would not be depriving them of routinely receiving the vaccination. Other viral infections such as Coxsackie B virus infection are associated with the development of islet autoantibodies. Therefore, the effectiveness of COVID-19 vaccination in preventing islet autoimmunity associated with COVID-19 infection will not prevent the occurrence of islet autoimmunity associated with other causes. The development of islet autoantibodies or type 1 diabetes may alter the behaviour of parents or guardians to the child and may affect further family planning or might cause psychological stress. Parental/guardian well-being is monitored via a psychological questionnaire. The development of islet autoantibodies may also affect the insurance options of the participant. Where is the study run from? Newcastle upon Tyne Hospitals NHS Foundation Trust (UK) When is the study starting and how long is it expected to run for? April 2024 to October 2029 Who is funding the study? Leona M and Harry B Helmsley Charitable Trust (USA) Who is the main contact?
Klinikum rechts der Isar Technische Universitat
Source: https://www.isrctn.com/