Clinical Trials on Pioglitazone
Guest: Dr. Dana King – Family Medicine
Host: Dr. Linda Austin – Psychiatry
Dr. Linda Austin: I’m Dr. Linda Austin. I’m interviewing Dr. Dana King, from the department of Family Medicine, about a really interesting new clinical trial that we have kicking off here at the medical university. Dr. King, tell us about the trial. First, what is the name of the study?
Dr. Dana King: The name of the study is The Effect of Pioglitazone on ADMA Levels.
Dr. Linda Austin: Now, let’s start off with ADMA levels. What does that stand for, and what is the significance of that?
Dr. Dana King: Alright. That stands for Asymmetric Dimethylarginine. That is a chemical in the bloodstream. The significance of it is that it has been found to be a risk factor in people with diabetes that increases their risk of cardiovascular disease. So, if you have elevated ADMA levels, you’re at higher risk, approximately double the risk. It’s similar to having elevated risk due to bad cholesterol, or elevated inflammatory markers in the bloodstream. It’s a new marker that people know less about but it’s equally important. And it’s been found to be separate from those things. So, it’s not measuring your cholesterol, and it’s not measuring your inflammation levels. It’s actually a byproduct of a system in the body called oxidative stress. It’s just a new marker of risk. The study is to see if this drug, Pioglitazone, can reduce those levels and, thus, reduce people’s risk.
Dr. Linda Austin: Now, Pioglitazone, is that known by any other name, or is it related to any other substance that people commonly know about?
Dr. Dana King: That’s the chemical name which we have to use in most situations. The brand name would be something called actos. That is an approved, currently used, medication for people with diabetes. It increases the sensitivity of your own insulin and makes your own insulin work better. It’s often used in combination with other medications with diabetes. So, we’re doing an experiment, but it’s not an experimental drug. It’s actually a medication that’s out there. We’re really finding out if it has, I guess you’d say, a new beneficial side effect.
Dr. Linda Austin: And is there reason to think the answer might be, yes? Have there been preliminary studies on this drug?
Dr. Dana King: There have. Of course, those were done in laboratory animals. And they found that when given Pioglitazone, the ADMA levels were lowered. There have been just a couple of uses looking for this particular marker in healthy subjects. But these, interestingly enough, were people that didn’t have diabetes. They just gave the drug to healthy volunteers, young people, college students, etc., to just see the effect of this medication on their ADMA levels. It was done in people that really didn’t even have such elevated levels, and it reduced them a little bit. So, we think it may be even more potent in a more target population that really has that problem.
Dr. Linda Austin: Now, do ADMA levels tend to be more elevated in patients with diabetes than in normal controls who do not have diabetes?
Dr. Dana King: Yes. ADMA levels are particularly elevated in people who are overweight, obese, and people with diabetes, and people with diabetes often have both of those conditions. So, those people have this elevated level. It’s an abnormal byproduct, or metabolite, I guess, or toxin, maybe. Maybe that’s not the best word, but an abnormal byproduct of having diabetes and being overweight.
Dr. Linda Austin: I see. So, if one were neither diabetic, nor overweight, there’d be no particular reason to get you ADMA level checked, correct?
Dr. Dana King: That’s correct.
Dr. Linda Austin: Do physicians routinely check ADMA levels, though, in obese diabetic patients?
Dr. Dana King: We do not, currently, because, you know, it’s early in the research history cycle and so it’s not a routine test that’s done. It can be done. It’s not a difficult test to do, but it’s not routinely ordered, you know, right now.
Dr. Linda Austin: So, if somebody wanted to enter this trial, first of all, is this being performed only here, at the medical university, or is this a multicenter trial?
Dr. Dana King: This is only being conducted here at MUSC.
Dr. Linda Austin: Okay. So, you’d have to be in this area, is that right? And, how long is the study?
Dr. Dana King: It’ll be going on over the next couple of years. We’re recruiting 36 people with diabetes to be in the study. They will take this medication and/or a placebo, or pretend version of it, for three months. So, they’ll take the medication for three months, have a little one month, we call it the washout period, maybe you should call it the rest period. You rest up for a month taking neither and then you’ll take the pretend one. Of course, you may take the pretend one first and then the other one, we don’t know, they’re going to look exactly the same, we won’t know, any you won’t know, which one you’re getting, unless, of course, we break into the secret code book. But, you’ll be taking them, they’ll look identical, and we just want to see the effect on your blood tests over this three-month period of time.
We are able to do this using only 36 patients because patients are acting as their own controls. Those of you that are familiar with these studies might say, usually these things are done on 100 people, or 200 people or, you know, 10,000 people. We don’t need to do that because it’s statistically very powerful when you act as your own control. It eliminates a lot of the random variation. The only thing that’s different in those two time periods is, basically, that you’re on this medication.
Dr. Linda Austin: Exactly. And then, after the sixth-month, or I guess it would be seven-month, period is over, do patients just go about their merry business? Or, if they wanted to stay on the medication, could they do that?
Dr. Dana King: They certainly could. When they enroll, we inform their physician of their initial blood work and also that they’re, you know, volunteered to be in this trial. And they’re, of course, getting Pioglitozone, or actos, or the placebo, or pretend version. And their physician would know when the trial is over and they would have the, I guess, option, you’d say, to continue on that medication. It’s available by prescription so they would get it, I guess, through the usual mechanisms, from their regular doctor.
Dr. Linda Austin: I see. Are there any adverse effects, or side effects, of Pioglitozone, actos?
Dr. Dana King: Well, yes there are. There are some warnings about, in the gastrointestinal system, nausea, vomiting or, I guess you’d say, some upset in the gastrointestinal system. The other main side effect, interestingly, is that it causes low blood sugar. Of course, that’s what it’s supposed to do. It’s supposed to work with your other medications. But the most common side effect is that your blood sugar will go lower. So, those people, perhaps their blood sugar is not at ideal levels, will particularly find this clinical trial, you know, perhaps, attractive.
Dr. Linda Austin: Are patients paid to be in the clinical trial?
Dr. Dana King: Compensation is available. They will receive a Walmart card each time they come and each time their blood is drawn; that’s actually seven times. Basically every month they’re in the trial, when they come, they get this remuneration, so there is compensation available.
Dr. Linda Austin: To some degree. And, of course, with these clinical trials, we don’t overcompensate because the thought is that people should want to do this not for money, or be tempted to do something they otherwise wouldn’t do, correct?
Dr. Dana King: And let’s not forget the, I guess you’d say, non-monetary benefits. In other words, a physical examination, actually, twice during the study, your blood work, which includes cholesterol, your hemoglobin A1c, your salt, your kidney function. All those things are done as part of the trial and are shared with your doctor and can be shared with you.
Dr. Linda Austin: Right.
Dr. Dana King: So, you’ll find out a lot of information about yourself, you know, through this trial that you might not otherwise get.
Dr. Linda Austin: You know, I think, though, that one of the most important reasons to participate in a trial like this is summed up by a woman I talked to, actually, yesterday, we were doing a podcast on kidney transplant. She had given her kidney for a stranger. I asked her what her feelings were about that, and she said she had never had such positive self-esteem knowing that she had done something to make a difference. And, when you do something like participate in a clinical trial with diabetes, you know, for someone getting diabetes, you think, why me, or this is so senseless. But at least this is something you can do to fight back, to give back, to contribute, to help make sense of the experience by helping the scientists and physicians who are really trying to understand and better treat people. It’s a huge contribution, and we really appreciate anybody who participates in a clinical trial as part of the MUSC team of researchers.
Dr. Dana King: Absolutely. The first person that I examined as part of this trial was actually a first-time study volunteer. She had never volunteered for a study before and I asked her why, and that was exactly her motivation. She thought that this might be helpful to people, and she thought it was something that she could do. So, it was just a pleasant surprise, you know, to have a first-time volunteer, who did not work at the medical university, but worked in the area, say, I heard about this and I just thought it would be great. And, you know, her experience of her first visit was certainly a positive one.
Dr. Linda Austin: And, I think it’s also important to underline that you just may help someone discover something that might really help you. I remember the first clinical trial I ever worked on was on obsessive-compulsive disorder. Our first patient had suffered from it for 50 years, and after a month on his medication, he was symptom free for the first time in 50 years. So, you never know when participation in a clinical trial will actually be of incredible benefit to you, yourself. It’s a really important thing to do.
Dr. Dana King: Well, and so, potential volunteers would ask themselves, well, what would be the ultimate outcome of this study if we were to find, you know, positive results, or find what we think we’re going to find, and continue on? And the answer is that, right now, this medication is sort of third in line for medications to use for patients with diabetes. But, this information, or perhaps other confirmation of it, this might become the second thing in line, or even the first thing in line, for patients with diabetes. So, it could potentially have a huge impact on what prescriptions people get in the United States. And if it has this positive benefit that other medications cannot provide, it reduces this marker that we didn’t realize was hurting us, that could be huge for patients with diabetes all over the country.
Dr. Linda Austin: And I would imagine, then, the next step in research, let’s say you are able to lower the levels of ADMA, wouldn’t the next step be to see if that actually does result in lower rates of heart disease? And wouldn’t that, then, shed light on how it is, exactly, that diabetes does cause increased rates of heart and vascular disease?
Dr. Dana King: Exactly. There are some other medications, kind of sister medications, or very similar ones, that actually do not have a positive benefit on heart disease. This one does, and this ADMA-lowering effect may be the reason.
Dr. Linda Austin: Oh, I see. So, it’s already known?
Dr. Dana King: It’s already known that this drug has at least a neutral and mostly positive effect on reducing your risk of cardiovascular disease, as opposed to other ones, other very similar medications. So we may be coming up with, I guess you’d say, the explanation. But, interestingly enough, of course, they weren’t following those levels, so it may also be a new test that needs to be done. You need to follow your ADMA levels and, you know, find other means of lowering that risk as well.
Dr. Linda Austin: Dr. King, this is really exciting and important research and I wish you luck. And I hope that anybody listening to this podcast, who has diabetes, will consider participating in the trial. Or, almost all of us know somebody with diabetes that we could give a call and say, hey, take a look at this! It’s a really important study. Thank you so much for this contribution.
Dr. Dana King: Thank you, Dr. Austin.
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