This is a straight forward clinical trial: people recently diagnosed with type 1 diabetes (in their honeymoon phase) will be given a standard flu vaccine to see if they will generate more of their own insulin as compared to people who don't get the vaccine. They are using a Sanofi Pasteur vaccine, VaxigripTetra™, which has been used for over 6 years in people 3 years and older. Previous versions of this vaccine have been in widespread use for decades.
They are recruiting 100 children (between 7 and 17) who have been recently diagnosed with T1D. This study is a standard, high quality study: it is blinded, randomized, and has a placebo control group. The primary end point is a C-peptide measurement (showing how much insulin the person is naturally producing), and there are several secondary and tertiary end points covering both patient results and internal immunology results.
They plan on gathering almost all of their data in the first year, but will monitor participants for safety issues for 5 years. This study started in Dec-2022 and they hope to finish in June-2026.
They are recruiting at four hospitals in Denmark: Aarhus University Hospital, Aarhus, Aalborg University Hospital, Randers and Gødstrup regional hospitals.
Contact: Ole Frøbert, MD, PhD ole.fro@clin.au.dk
(There is additional contact information in the clinical trial registry.)
More Information
Clinical Trial Registration: https://www.clinicaltrials.gov/ct2/show/NCT05585983
Discussion
For me, there are two interesting discussion points (and one uninteresting discussion point).
The obvious question is: why do the researchers think it will work?
The researcher, Ole Frøbert, recently published a study showing that flu vaccine administered shortly after a heart attack reduces the ongoing risk of death. Heart attacks come with high levels of inflammation and he believes that flu vaccination lowers this inflammation, causing the good outcome he saw. While flu vaccination raises immune response in general, it also lowers specific inflammation signalling. It is well known that in T1D inflammation is an important path for the destruction of beta cells, causing the start of the disease (or at least the start of the symptoms and the need to inject insulin). This researcher believes that flu vaccination lowers inflammatory signaling for the specific targets which are doing the damage in T1D. These targets are discussed in the following paper: https://pubmed.ncbi.nlm.nih.gov/34326232/
I have not found any previous research testing if flu vaccines have any impact on existing T1D.
But there is good evidence that people with T1D get flu more than others, which is why people with T1D should get yearly flu vaccinations. A recent summary is here: https://www.frontiersin.org/articles/10.3389/fimmu.2021.667889/full and recommendations to do so from the CDC and the ADA are linked here: https://www.healthline.com/health/diabetes-and-flu-shot.
There are also many studies showing that flu vaccines do not cause T1D and are safe for people with T1D. I have summarized these studies here:
https://cureresearch4type1diabetes.blogspot.com/2015/10/seasonal-flu-vaccine-and-type-1-diabetes.html
and here is the statement from the US National Academies of Science, with many supporting links:
https://www.nationalacademies.org/based-on-science/is-it-possible-for-the-flu-shot-to-cause-type-1-diabetes
The big issue for me, for this trial is: should I blog on it? Is this research aimed at a cure or are they just hoping for better control, maybe using less insulin? I blog on the first kind of research, but not the second.
When it is not clear if the researchers are aiming for a cure or a treatment, I look at what they are measuring as their primary result. C-peptides are a measure of insulin production, so if that goes up, it can (at least potentially) lead to a cure. On the other hand, blood glucose levels, A1c, and insulin usage are all treatment-oriented measures. For this study, the primary outcome measure is C-peptides, so I'm treating it as cure focused. They are also measuring blood glucose, A1c, and insulin levels, so if it turns out to have results that help treatment (but not cure), then I'll stop covering it.
The investigators certainly do not expect that the influenza vaccination will cure type 1 diabetes in this trial. However, even a modest improvement in insulin generation would suggest a new research direction into a possible, future, vaccine based, cure.
The uninteresting discussion point is this: will it work?
The answer is simple: we don't know; that is the whole purpose of this trial. Since the trial is fully funded and underway, there is no reason to speculate as to whether or not it will work. All we need to do is wait and see. Guessing as to outcomes is a waste of time.
Note: I classify this study as phase-II? because it is the size of a phase-II study, but the treatment has never been tested on people with T1D. Therefore, there is no T1D data available from a phase-I study, so I call it "phase-II?". Officially, it is phase-IV, because it is being done after the vaccine is on the market.
