Before hydroxychloroquine was part of the national Covid conversation, it was being looked at in studies to see if it might help in the prevention of type 1 diabetes. Recently JDRF held a Facebook Live event with Dr. Jane Buckner, where she talked about TrialNet’s Hydroxychloroquine (HCQ) Prevention Study. JDRF was kind enough to share the audio with us for this week's show.
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Stacey Simms 0:00
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This week, we're talking about hydroxychloroquine. Yeah, that's right before it was part of the National COVID conversation is being looked at in studies to see if it might help in the prevention of type 1 diabetes.
Welcome to another week of the show. I am so glad to have you along I am your host Stacey Simms. We aim to educate and inspire about type 1 diabetes by sharing stories of connection my son was diagnosed with type one more than 30 years ago, he was a toddler at the time and now he is 15. My husband lives with type two. I don't have diabetes. I have a background in broadcasting local radio and television, we decided to get the podcast, which is now more than five years old. So if this is your first episode, thrilled to have you here, please go check out the website Diabetes connections.com. We have a very robust search we have more than 300 episodes now. So there are ways to get to it by date by keyword by subject matter. If you'd like to go back and start it episode one. You can use any podcast app as well. Wherever you listen to audio at this point, you can get this podcast.
This week's show is unusual in that it's not an interview, as I usually do. Recently, JDRF held a Facebook Live event with Dr. Jane Buckner, where she talked about TrialNet’s hydroxychloroquine prevention study JDRF was kind enough to share the audio with me. I found this so interesting like most people, I heard About the drug this year because of the whole conversation about COVID and could it treat it and that sort of thing. Many of you probably knew about it long before that in relation to lupus and arthritis and malaria, but I didn't know it was being studied at TrialNet.
So you'll hear from Dr. Buckner in just a moment but first diabetes Connections is brought to you by One Drop. It is so nice to find a diabetes product that not only does what you need, but also fits in perfectly with your life. One Drop is that it is the sleekest looking and most modern meter My family has ever used and it is not just about their modern meter setup. You can also send your readings to the mobile app automatically and review your data anytime. Instantly share blood glucose reports with your healthcare team. It also works with your Dexcom Fitbit or your Apple Watch. Not to mention their awesome test strips subscription plans, pick as many test strips as you need, and they'll deliver them to your door. One Drop diabetes care delivered, learn more go to Diabetes connections.com Click on the One Drop logo.
Dr. Jane Buckner is the president of Benaroya Research Institute at Virginia Mason in Seattle. She's also a rheumatologist who takes care of patients with rheumatoid arthritis and systemic lupus. She studies type 1 diabetes as well and is the co chair of the hydroxychloroquine study at TrialNet. Now, we've talked about TrialNet, and we've talked to TrialNet, or at least the people who work there. Many of you know that group as the people who will test your child's siblings or you or other family members for markers of type 1 diabetes, but they are tasked with the mission of finding out how to prevent type one. And so testing is just part of that. I mean, that's really where they get the ball rolling, but they have some incredible studies and I will link up more information and more episodes that we've done. We've done several with trial that I'm a big fan and I'm a big fan of anybody who takes part in their research going through those studies. Just having a family member tested. I think that's a big deal. And we should applaud everyone who does that.
Quick note, again, this is more of a speech, right? I edited out some of the stuff here to Facebook Live the pauses, stopping as she reads the questions to herself. There are some beeps, there's some audible noises I couldn't take out but it's really fine. All right, here is Dr. Buckner, just after she has introduced herself and her role at TrialNet.
Dr. Jane Buckner 4:25
And so we'll talk about a little bit about TrialNet first and then talk very specifically about this prevention of type 1 diabetes using hydroxychloroquine. Why did we pick this drug? How are we doing the study? And then also we'll talk about how to participate and take questions. Type 1 diabetes TrialNet is the largest international type 1 Diabetes Research Consortium comprised of over 100 locations and its mission is to prevent type 1 diabetes and stop disease progression by preserving insulin production before and after diagnosis. And so there's In a series of studies, there's a pathway to prevention. That's what we call a natural history study where we screen people who are at very high risk for developing type one diabetes, and we monitor them over time. We also do intervention trials in new onset diabetes. And we are now doing trials to prevent development of diabetes.
The other part of the work we determine that where I've been really involved over the years is what we call mechanistic studies. When we do a clinical trial, we can go back to the lab and we can look at the blood samples from patients and try to understand why a certain intervention worked are help slow the progression of diabetes or loss of insulin production, or why it didn't work. And so that's where I've been involved over the years thinking about type one diabetes and what got me interested in this clinical trial.
So why is TrialNet testing hydroxychloroquine to prevent type 1 diabetes? The first thing we need to talk about is thinking about type 1 diabetes. As a disease that progresses over time, we know people are born with a genetic risk, particularly relatives of individuals with Type One Diabetes children, or siblings of individuals with type one diabetes have a much higher risk of getting diabetes. And that's because of their genes. We know at some point along the way, in some people who have that genetic breast, their immune system gets activated, and they begin to develop immune responses that target the beta cells in the pancreas.
What we've learned over the years, with the studies done by many scientists, but including those in town, that is that there's several stages to developing diabetes. There's stage one, which is where people have to autoantibodies but their blood sugar is still normal, and their pancreas is still functioning well, they don't know that diabetes, but in fact, they are on the road to developing diabetes and it's just a matter have time, at stage two individuals have these auto antibodies, that they now are starting to have abnormal blood sugars. And finally, at stage three is when we think of the classic clinical diagnosis of diabetes where individuals require insulin.
Well, so the goal is actually, in this study, to prevent people from going from stage one, to stage two or stage three. The idea is if we treat people early at this very early stage of diabetes, where they have the immune response already targeting their islet cells that make insulin, if we could stop it from actually continuing, then we could actually keep people from getting clinical disease. So that's our goal with this study. So why did we pick hydroxychloroquine and in part of the story here is that I'm a rheumatologist and rheumatologists use hydroxychloroquine to treat many autoimmune diseases, particularly rheumatoid arthritis and systemic lupus, it's an oral therapy. It's a pill that you take once or twice a day. And it's used in these diseases and has been used Actually, it's a drug that's been available for over 60 years, initially developed to treat malaria. But in studies used by rheumatologist, it's been demonstrated to be very useful in rheumatoid arthritis and lupus. It's FDA approved to use in children and in pregnant women. And I have to tell you, it's not common a drug is considered that safe to do both of those.
we know a lot about this drug. We know a lot about how it works, but more importantly, we know about side effects with this drug. So why should we think about it? Well, there's clear efficacy in lupus and rheumatoid arthritis that we know and I'm just going to say that one of the things we also know about lupus and rheumatoid arthritis is that there are diseases where people make auto antibodies that target different parts of them. body. We know those autoantibodies happen before individuals come in to see their doctor with these diseases and they predict development of the disease. There's been small studies that have been done that suggests that taking hydroxychloroquine before someone who gets a disease, let's say they have their very high risk for the disease, they have a relative who has rheumatoid arthritis or lupus or they have some initial signs of those diseases. And these early studies suggested that they may well prevent development of the full blown disease. And actually this idea of using hydroxychloroquine early before people develop clinical disease has also now part of large clinical trials in both individuals at high risk for rheumatoid arthritis. And a study for people at high risk for lupus and the rheumatoid arthritis study is called stop ra where individuals who have auto antibodies or have relatives and are at various high risk for the disease or start on hydroxychloroquine early and they're following them to see if they develop rheumatoid arthritis or if hydroxychloroquine actually prevents the disease.
at trial that we were talking about what would be a good intervention to use to try to stop that progression from stage one to stage two and stage three, what would be safe enough for us to give children and people who were otherwise healthy, and also had made sense from an immunology point of view, and that's why we chose hydroxychloroquine. What we're doing in this trial is thinking about how type 1 diabetes starts, and that stage one where there's two or more autoantibodies, but normal blood sugar, and our goal is to stop at that point so that we can maintain a normal blood glucose and stop beta self destruction. The goal is to delay conversion to stage two and that would be having auto antibodies and abnormal glucose tolerance and to maintain that current level of beta cell function. And so the way we design this study was to actually look for individuals who are participating in the trial on that pathway to prevention, who we know have two or more auto antibodies, but still have normal glucose tolerance. So they're stage one.
And because this drug has been used in in young children, we're able to start as early as age three. But we also are including adults as well. This is a study where it is placebo control, two out of every three participant will get the study drug, and the others, one third, we'll get received the placebo. This is really important in clinical trials, because we have to know not only if the drug works, but we also need to make sure that it doesn't cause harm. And this placebo control group helps us know both of those answers.
This is a randomized trial. So a computer randomly selects who gets the study drug, and it's double blinded. That means no one knows Who is in which group until the end of the study and that includes the clinical coordinators, physicians who are participating in working with study participants. So some of the details and safety has become an issue that's much more on people's mind because of the use of hydroxychloroquine in the setting of COVID-19. And I can speak particularly to that as well. But let's first start by remembering that hydroxychloroquine has been used for over 60 years and is FDA approved for pregnant women and children. When we started considering the use of this drug. We worked within TrialNet with a group of infectious disease experts for study design, and we also monitor all the side effects throughout the study. Importantly, we know from treating particularly patients with lupus and rheumatoid arthritis, that adverse outcomes or safety issues are linked to the dose of the drug being used, the length of time that it's used other medications that a patient may be on.
So when we do this study, we screen people who are participants for potential complications at the time that we randomize them. But we continue to follow for those at the time of the study. And I can go into more detail about this. Since we've been recruiting for this study. For over a year. Now, we now have a very good sense as well, not only from historical results with our patients from the rheumatology clinics, but also from the individuals participating in this trial. And just a few things about this trial. So, participants, this is a capsule that's taken by mouth as instructed. And our goal is to have people in this study taking this drug until they progress to stage two, that's the abnormal glucose tolerance, or stage three, which is diabetes onset. So it's it's a study where the participants are in it for several years. They have an initial study, visit, followed by three months, six months, and then every six months we see the participant in the study visits last three to four hours. And of course, all of our treatments and exams are provided at no cost.
Here we have one of our study participants, Laila who's for taking her study medication, and you can check out her video online. Just a little bit about how to participate. The first step is to enter pathway to prevention, which is the TrialNet study where anyone aged two and a half to 45, who has a sibling, a child or a parent with Type One Diabetes is encouraged to participate and be screen. But we also broaden that to include not just your parents or siblings or children, but also Uncles, aunts, nieces and nephews. And we have quite a large group of participants in this and this gives us the ability to screen to see if you would be a person who has those two auto antibodies and would be qualify for this study. And to do that you can visit the trial on that site that we do home At home test kit. So this can much of this initial work can be done at home. And then we can have you in touch with people to understand if you would be a good participant for this.
So I'm going to take questions now and I will go into more depth about hydroxychloroquine safety and try to answer other questions. The first question is, do you have any intervention trials currently recruiting? And so this is actually a really interesting question because TrialNet always wants to have intervention trials ongoing. So we have a series of trials in nuance at type 1 diabetes, and then we had just opened another trial in individuals who had to auto antibodies and abnormal glucose tolerance. Some of those trials are on hold, and that is because of the covid 19 pandemic there has been concerned about using medications that may suppress the immune response. So currently We are following the patients who have already received treatments. But we are not bringing on new subjects at this time. I would say our goal is to do that once we have a better understanding about how to move forward. But really interestingly, hydroxychloroquine is not considered immunosuppressive we started that trial in the summer of 2019. And we have continued that trial throughout the pandemic because it was felt that it did not put our our subjects at increased risk. And of course, at one point, there was thought that it may be helpful. We have asked our participants to continue taking their medications as prescribed throughout this period with the COVID-19.
Yeah, so one of the questions is Could this be of any benefit to long standing diabetes patients who have no c peptide? And part of this issue is this beta cells that are stunned, so may be able to recover? That's one of those really interesting areas, and I think that the jury is out on that. Part of the reason that we decided to study hydroxychloroquine in these individuals who are in stage one is we think the role that hydroxychloroquine may play may stop the immune system, what we know is the immune system gets activated, and then it's a little bit like a steamroller, increasing and increasing in its aggressiveness against the body and against particularly the beta cell. And our hope was to stop it early before it picks up too much speed. And that's what we think hydroxychloroquine doesn't mean that it might not be helpful in this setting where we may have beta cells that are our stun and and it may become useful in individuals where once we've cooled down the auto immune response, maybe with another medication, that this may be a drug that we could use long term to maintain that kind of tolerance or quiescent stage. So I think we'll we'll have a better idea when this first trials done.
Yeah, so the next questions is have have we seen any patient with negative side effects that you've heard so much about, and I know a lot of people are nervous because of what they've heard on the news, and so I kind of wanted to relate our experience. The first thing I could say is that we have our experience with our subjects in this trial, but as a rheumatologist, I have been prescribing this drug for, I hate to say it, but almost 30 years. So I've been been taking care of patients with lupus and rheumatoid arthritis who have been taking hydroxychloroquine throughout my career, because this is a drug that's been used for a long time. And I'd also like to say those patients take the drug, many of them for 10 or 20 years. So my experiences that and our experience with our subjects in this trial is that some people do have some side effects. Most of them tend to be more like some mild gi upside, initially, maybe a side effect. We also have to watch out for the eyes in this setting. We know that long term use of this drug can impact the eyes, so participants get regular eye exams as part of the study. So if there's any problem, we capture that quickly, and we have ophthalmologists who help us with that. There's also been concerns about cardiac arrhythmias with this drug. And that's been, you know, highlighted in the setting of COVID-19. I think it's important in that setting to understand that dose matters. And in some of those clinical trials, where we saw cardiac arrhythmias in COVID-19 patients, the doses were higher than we are using. The second point is that those individuals are under are extremely ill and in fact, are having some potential cardiac problems as part of their disease. So I think that's really quite different than what we see in a pattern in our patients in this trial and what I see with my patients with rheumatic diseases, that being said, the other issue is when you give this drug with other drugs that can aggravate or bring out a potential a rasmea We have been very careful throughout this study to have a large list of medications, we track those. And if it if one of our study subjects takes a medication we think could complicate it, we may hold the drug for a while. Right? And then one of the questions is about the dose, and we do select a dose for patients based on their weight in size. And the dose that our patients, if they're a full sized adult would take would be the same as the dose that I would be giving a lupus or an RA patients, for example. The next question is, is there any promise here that if beta cells are replaced in someone who has diabetes that hydroxychloroquine could prevent those new beta cells from being killed off? It's another really great question that we think about a lot at trial that, you know, again, I think with islet cell transplant, or pancreas transplant, you're probably going to need a stronger medication to control the immune response against that transplant. So at this point, I would say it could help After that initial immune response was controlled, but probably not initially, I would suggest that we would need a stronger immune suppressant drug because it's a transplant.
I have a question about Can I tell you about why I think hydroxychloroquine will delay and prevent onset of type one. So that is one of those very interesting questions. So we've been using, as I said, hydroxychloroquine in the setting of lupus and rheumatoid arthritis for I think, 40 years in Rheumatology and myself for 30 years, and we've learned a lot about the immune system over the last 40 years. So when it was first used, really no one knew why it worked. They just knew it worked. And of course, that's the most important thing for patients. What's happened as we've gotten smarter about immunology is people have devseloped a much better understanding particular about why hydroxychloroquine work and lupus We think the auto antibodies are triggering an inflammatory response. And hydroxychloroquine actually acts within the cells to stop that triggering of the response. It's something called toll like receptor activation. So we think it, it stops some of that kind of unusual or abnormal activation of the immune system. But it also has an impact on how the immune system kind of shows that something's foreign and you should attack it. And hydroxychloroquine can actually impact the ability of presenting what we call self antigens to the immune system. And I think that's a really important part of this communication. There's a communication between B cells and T cells that I think it's really vital that it's impacting, and that's why I think it's going to be important in people who only have two auto antibodies but haven't moved further yet. One of the things we might think about doing after this trial is to even go earlier for those people who only have one auto antibody, who may not get Type One Diabetes if we could get in there even sooner, and we think that might be a good place to intervene. The question is, how long after diagnosis can be enrolled in a new onset study and each study that we do we have a particular plan to enroll for new onset. And so I think that is important to be in touch with TrialNet and find out what study would suit you if you have been very recently diagnosed. There are typically some studies that quite a few studies that enroll but we also are interested in some studies where people who've had diabetes for a while may help us understand the disease better. One of the other questions is have we thought about trying this in stage two or stage three, and we have not we have talked about where we think this drug would be most effective, and we thought stage one or even the single autoantibody high risk individuals would be where it would be be most effective. So we wanted to do that trial first. And if it's effective there, we would obviously then think about moving in into later stages. Those are all the questions I've seen. I really appreciate that you've taken the time to spend with us today. To hear a little bit about this study. I'd like to encourage anyone who has more questions or is interested in participating in any of the studies and trial mat, whether that's pathway to prevention, or one of our clinical trials to please contact TrialNet. Thank you very much, and I hope you have a great rest of your day.
You're listening to Diabetes Connections with Stacey Simms.
Stacey Simms 24:46
More information and if you'd like to watch that as well, I will link it all up at Diabetes connections.com. But as usual, with our episodes beginning in 2020, we are providing transcripts for all of these episodes. So if you know somebody who would rather read Then listen, go ahead and check it out. And if that's maybe you, you can go back. And listen, I'm trying to add in more transcripts for previous episodes, but it is from January of 2020. On if you're looking for that, and I have a question for you, and I have a deal for you. So stick around for just a moment.
But first diabetes Connections is brought to you by Dexcom. And we started with Dexcom. Back in the olden days before share, gosh, we've been with them for a long time. So trust me when I say using the share and follow apps make a big difference. Benny, and I set parameters now but when I'm going to call him how long to wait, that kind of stuff. It helps us talk and worry about diabetes less. You know, if he's asleep over away on a trip, it gives me so much peace of mind. It also helps if I need to troubleshoot with him because we can see what's been happening over the last 24 hours and not just at one moment. The alerts and alarms that we set also help us from keeping the highs from getting too high and help us jump on Lowe's before there were a big issue. Internet connectivity is required to access separately Dexcom follow app to learn more, go to Diabetes connections.com and click on the Dexcom logo.
So I said I had a question and a deal. So here's the question. What do you think of episodes like this, where it's not an interview, but I'm bringing you information that has been, you know, already put in the world via a Facebook Live or somebody giving a speech or a conference presentation, whether it's virtual or in person? Do you want to hear more of that I've done this sporadically over the years. Personally, I love it because I can't catch all the stuff that's going on right now. I did not see this Facebook Live as it was live. But I wanted to make sure to catch the information. So if this is something that works for you, let me know because I'd love to reach out to more diabetes organizations that are doing things like this and see if we can give a kind of a second life to some of the stuff that they've done. We don't want it to be one and done right if it goes out there once did it work for you? Is it okay that you didn't see her She did have slides. I listened without the slides. And I didn't think it really made a big difference to me. But if it did to you, if you felt confused, let me know. I'll see if I can grab the PDFs from JDRF. I'm not quite sure how to share those in the show notes. But hey, we can try. So that's the question.
And the deal is the world's worst diabetes mom is on sale. And this is kind of a two fold thing. So it's on sale at the website at Diabetes connections.com. If you use the promo code FFL2020. That was for friends for life, the virtual conference that happened earlier this month, that promo code will save you $4 off of the cover price. Again, it's FFL2020. And Amazon has also dropped the price of the paperback as of this taping. Amazon doesn't alert you when it does this. It just it just does it and I have a feeling it's because of the special we ran in the sales were making on the website, but they dropped it as well. And if you're a Prime member, of course you get free shipping. So I sign books that come through the website. I can't see seiner personalized books that go through Amazon, but it's on sale in both places. No promo code needed on Amazon do not know how much longer it'll be for sale like that on Amazon. But the ffl 2020 promo code is only good till the end of July. So go get it. Speaking of friends for life, the next episode should be just a couple of days from now I'm working on a bonus episode of the faithful Woods squares. This was the game show that I did it friends for life, and we're putting out video form but I'm also going to put it in podcast form just to cover all the bases. So hopefully that'll be out in just a couple of days. And you can enjoy that it really was fun. I'm so glad it turned out well, what are we going to do next? I got more requests to do Hollywood Squares again or FIFA with squares. I usually do a take off of NPR is a Wait, wait, don't tell me as we don't poke me. But I'm kind of thinking about doing some kind of Family Feud?
Stacey Simms 28:53
All right. Let me know what you think. Thanks, as always to my editor John Bukenas of audio editing solutions. Thank you so much. much for listening. I'm Stacey Simms. I'll see you back here for our next episode until then, be kind to yourself.
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