Verapamil is a drug which has been used in the US since 1982 for high blood pressure, migraines, and heart problems. It also lowers levels of a protein called TXNIP. Some researchers believe this is important because they believe TXNIP kills beta cells as part of the onset of type-1 diabetes. So giving Verapamil should lower TXNIP which should improve beta cell survival, and stop type-1 diabetes. In addition TXNIP is known to lower inflammation, and that might have an effect on type-1 diabetes as well. Verapamil has already undergone phase-II trials for T1D in the United States, which I discuss below.
The Ver-A-T1D Study
This is a 138 person study, randomized, controlled, and double blind. It is for adults in the honeymoon phase (within 6 weeks of diagnosis). Half the participants will get Verapamil for a year, the control group will get a placebo. All will be followed for a total of 2 years, so one year while they get the drug, and then one additional year. The study started in Feb-2021 and is expected to end in May-2023.
The primary outcome is a measure of C-peptide generation, which measures how much insulin a person is naturally generating. There are 10 secondary outcomes, mostly measurements of C-peptides, but also insulin use, proinsulin generation, BG in range, and A1c. There are a few tertiary (or "other") outcomes, which are quality of life questionnaires.
This trial will recruit in 22 different locations, at least. These sites are all over Europe and the United Kingdom. There is a list in the clinical trial registry below, but the exact status of each site might be out of date. If you are unsure if one of the listed sites is actually recruiting, you can contact the study organizers here:
Martina Brunner +43 316 385 ext 72841 martina.brunner@medunigraz.at
Karin Brandner +43 316 385 ext 72800 karin.brandner@medunigraz.at
Clinical Trial Registry:
https://www.clinicaltrials.gov/ct2/show/study/NCT04545151
The European Clinical Registry number is 2020-000435-45.
This study is being funded by the JDRF, among others.
Discussion
There are a couple of interesting discussion points here.
What happened last time?
This is the second phase-II trial for Verapamil. I blogged on the previous phase-II trial here:
https://cureresearch4type1diabetes.blogspot.com/2018/09/results-from-phase-ii-verapamil-trial.html
So, for me, the most important question for any T1D cure that has been tested previously is, how did it work before, and why do we think it will be better this time? This is especially true for a trial like Ver-A-T1D, where the dose and duration of the study is the same as the previous study.
The results from that trial were definitely interesting. The visual summary of that study is here. Remember that people in the study were given the drug for 12 months:
My summary:
- For three months after treatment, C-peptide number went up, and this is great news. That is on the path to a cure. However, after three months, C-peptide numbers went down and did so at basically the same rate as the untreated (placebo) group.
- The treated group started out at a noticeably higher C-peptide level than the untreated group. That is not a good thing. The two groups should start out the same.
Clinical Trial registry for the earlier study:
https://clinicaltrials.gov/ct2/show/NCT02372253
INNODIA and T1DUK
This study is part of the INNODIA and T1DUK networks. INNODIA is a European collection of research universities, commercial companies, and patient organizations aimed at fighting T1D. Their research goal is "to advance in a decisive way how to predict, stage, evaluate and prevent the onset and progression of type 1 diabetes (T1D)." T1DUK is a UK collection of research universities focused on Immunotherapy research. Its principal aim is "To help get immune therapy into the market as part of the management for type 1 diabetes". Both networks are funded by JDRF. T1DUK is also funded by Diabetes UK (and others) while INNODIA is funded also funded by the Helmsley Trust (and others).
I plan to blog on both of these research networks in the future, but in the meantime, I view them as similar to TrialNet in the US.
Recruiting Issues
(Children vs Adults. Honeymoon vs Established. Money and More Money)
This study is using 22 different sites to recruit 138 people. Think about how expensive that is. Each site must be staffed, trained, and supported. They are expecting to be able to recruit about 6 people per site (on average). Why so few people? Well, they are recruiting adults because of safety concerns and a general regulatory assumption that clinical trials should be run on adults when possible.
But these assumptions create problems for T1D research. Most people with T1D go through their honeymoon phase as children, so if recruiting for a honeymoon treatment is limited to adults, most people are excluded. And if most people are excluded, then you need to cast a very wide net to get the people you need, and that adds to the expense.
For this trial, there is the question of, why limit it to adults? The drug they are testing is already approved. Although the disease it is approved for affects adults, there are no age restrictions on the approval. It can be prescribed to children. More specifically, it has already been tested in people with T1D, so it would be quite reasonable to test it on children in this, the second, T1D study done. But they chose not to do this. That decision is going to result in a more expensive and slower clinical trial, which is too bad.
The study will not finish in May-2023.
Although the plan is for the study to finish in May-2023 (as listed in the clinical trial registration), we already know that it will not. How? Because the study is still recruiting people now, and once those people are recruited, it takes 2 years to gather the data. Therefore, the study can't possibly finish before Feb-2024. (Unless they have finish recruiting and just forgot to update the clinical trial registration. That is possible, but unlikely.)
