COVID-19 African American Nitric Oxide Breakthrough Study with Dr. Nathan Bryan, PhD

This week I interviewed Dr. Nathan Bryan, who describes why there is a racial disparity when it comes to COVID-19 deaths, hospitalizations, and diagnoses. More importantly. Dr. Bryan created NOviricid which is undergoing FDA-cleared clinical trial. Learn more at aacovidstudy.com

Transcript

Cheng Ruan  0:02  
Everybody, it's Dr. Ruan. And I'm really excited today to introduce to everyone Dr. Nathan Bryan, PhD.  Dr. Brian completed his undergraduate the the Bachelor of Science in Biochemistry at the University of Texas at Austin, got his doctorate from Louisiana State University School of Medicine in Shreveport, LA.

He has multiple awards and decades of research on this topic on nitric oxide, which we'll touch on today. Dr. Nathan and I have decided that it's really time to focus on some racial disparities of how COVID-19 is really affecting the African American population

from mechanisms that not everyone may know about, which are these nitric oxide mechanisms. And so we're going to keep it real simple. And also let you guys know, we are doing a clinical trial. It's in multiple cities right now. I'm hosting the Houston center up it's also in what is it? Atlanta, right?

Dr. Nathan Bryan  1:13  
Study sites in Chicago, in Houston,

Orlando, Jackson, Mississippi, and Augusta, Georgia, 

Cheng Ruan  1:24  
And maybe more to come? We don't know. Right.

So let's let's dive into this. Because I think this is a topic that not many people know about. And so let's let's dive into "the why". Why was a study design in the first place? And what's your background in nitric oxide? And, and also why now? 

Dr. Nathan Bryan  1:50  
Yeah, very good point. And thanks, Dr. Ruan, for having me. Having this discussion is very important. See, I've been in the nitric oxide field for more than 20 years and have published hundreds of peer reviewed papers have over two dozen issued U.S. and international patents. And so I've really been trying to figure out what goes wrong in people that can't make nitric oxide, what are the clinical consequences? And then how do you fix these problems. So that's kind of the background of kind of my world in the nitric oxide space. And it's recognized that loss of nitric oxide is really the earliest event and the onset and progression of many, if not most chronic diseases. So we've been trying to develop safe and effective therapeutics, nutritional products for for more than 10 years now.

And we had drugs that we were trying to develop for heart failure, pulmonary hypertension, coronary artery disease, and then COVID came. And over the past 10 months, we've learned a lot in COVID, that they're very susceptible populations that have an increased rate of infection, increased risk of hospitalization, and you know, a higher mortality rate. And one such population is the African Americans. They represent 13% of the US population, but they're about 50% of COVID deaths. And so that's really ... the health disparities of African Americans have been known for many, many decades. The African Americans have a higher incidence of high blood pressure, diabetes, heart disease, kidney disease, some forms of cancer. And about 20 years ago, it was recognized that due to both some genetics and, and lifestyle issues that African Americans have a higher rate of endothelial dysfunction, which means that they produce lower nitric oxide than most other ethnic groups. And that actually explains the health disparities. So why COVID so what you know, it takes many years and to get a drug approved from start to finish, you know, we've had safe and effective nitric oxide technology on the market for more than 10 years. So with COVID, we recognize that the increased risk of infection, the increased rate of the rapid progression of disease and need for hospitalization, ventilation and death, was all due to insufficient nitric oxide. So it just made sense to us to implement a nitric oxide therapy to normalize their nitric oxide levels. And then by all bets, we could prevent the rapid progression of disease, the need for hospitalization, the need for ventilation because nitric oxide controls oxygen delivery and oxygen uptake. And then if you do that, you decrease mortality. So we submitted an investigational new drug application to the FDA earlier this year, and we got that approved and cleared several months ago. And now the work is to be done. And thanks to you, we've got a clinical site up and running in Houston. And so we're looking for African Americans aged 50 to 85, with at least one underlying comorbidity with that being high blood pressure diabetes, obesity, smokers, pulmonary disease, kidney disease, if there's one or more of those, and you're diagnosed with COVID within 72 hours, then you're you're a candidate for enrolling in this study. So that's the patient population, we've gone to hotspots. Obviously, this is a ripe time for a clinical trial and COVID. And so that's, that's the why. And we think that we can impact this particular population, very vulnerable, very susceptible population to COVID. And really, I think, save hundreds of thousands, if not millions of lives. 

Cheng Ruan  5:30  
Right. Thank you for that Dr. Brian. So one thing I do want to bring up, and it's kind of like the elephant in the room, because this is a huge time of mistrust in the nation. And I think that there's a lot of vaccines and a lot of drugs that are developed out there. Right? What makes what we're studying now, so important to not just African Americans, but to everyone. What's unique about this? Is it safer?  Is it more natural, what is it? Is there some sort of chemical component that doesn't do as much detriment as other drugs? What's unique about this?

Dr. Nathan Bryan  6:12  
Yeah, it's a very good question. And I think it's worth mentioning that this is not a vaccine. This is classified as a therapeutic. You know, it's known that about half the U.S. population really do not want to take a vaccine. And as much as 65 to 70% of African Americans are a little bit distressing and aren't in favor of getting vaccinated. So what we do is we develop safe and effective therapeutics, which is completely different. And this is different than most drug discovery programs, because I apply principles of applied physiology, which means that we understand the mechanism of disease to the extent that we can fix the underlying problem within the human body. So nitric oxides naturally produced, from the time we're born to the time we die, we just lose it over age. And so we're looking to simply restore normal physiological production of nitric oxide. And what we've learned about COVID, what we've learned about the so called long hauler, or the increased risk of blood clotting, and stroke, and embolism and blood clotting disorders, can all be attributed to lack of nitric oxide production. So what we're doing in our therapy is basically repleading back what's missing in the susceptible and vulnerable populations.

Cheng Ruan  7:25  
Okay, so it's interesting, because, when most drugs are developed, it's for a specific biochemical thing that happens in the body, right? And it's like, you know, there's blood pressure pills, but you're not really born with a blood pressure pill deficiency. There's antacids, you're not really born with an antacid deficiency. Right? So this is really looking at the root cause, because you do have a nitric oxide deficiency, if maybe you have poor lifestyle habits, there's racial disparities, toxicities, and poor diet and stuff like that, right. And so this is really the first thing that I really seen that deals with the underlying dysfunction as a root cause effect, and trying to prop ourselves up from the root cause effect, in effect and disease outcome. Right. And so that's why I'm really excited to be to be involved with this. So let's talk about the study drug a little more, what is what is the drug called?

Dr. Nathan Bryan  8:24  
The drug is called NOviricid. So we had a play on words and NOviricid means "cidal" or "cid" means means kill. So NOviricid means "kills the virus". And, "NO", as a prefix is like the nitric oxide kills the virus, or NOviricid. So what this drug is, it's it's an orally disintegrating tablet. So I think it's worth mentioning that nitric oxide is a gas.  It's naturally produced in your body. So when it's produced, it hits its targeted and elicits some cell signaling events, and basically has some physiological function. So this lozenge actually when it's dissolving in the mouth actually generates the nitric oxide gas. So if your body can't make nitric oxide, which is the African Americans that are infected with COVID, then we do it for you. So we provide that rescue dose of nitric oxide, it'll open up your blood vessels, it'll improve oxygen delivery, we're seeing blood oxygen levels build from the mid to high 80s into the 90s within 10 or 15 minutes. So we see the physiological effects of them. And the interesting thing is nitric oxide's also antiviral. There's published studies out there showing that nitric oxide can prevent or inhibit virus replication. So if you're exposed, the normal innate immune responses that are white blood cells and immune system becomes mobilized. We generate a lot of nitric oxide, nitric oxide prevents the virus from replicating and you don't get sick for symptoms. But in people that can't make nitric oxide, the virus takes root, rapidly replicates, rapidly is transported throughout the body and affects many cells. You get very sick you lose the ability to transport oxygen, you get hypoxemia, and you've the need for hospitalization, you have to put on a vent (ventilator). Once you're on a vent, the prognosis is very poor. So with hundreds of thousands, or millions of patients now been diagnosed, most people recover. But we know they're populations that do very poorly. And that's the African American population, we hope to reverse that course. 

Cheng Ruan  10:20  
Great. And so the next question, the most common question is why African Americans, we just look at the CDC studies, you know, African Americans have 1.4 times the cases, compared to, these are the rate ratios, compared to white non Hispanic persons on the CDC website as of today, which is December 16, 2020. Rates of hospitalization in African Americans is 3.7 times higher, and the risk of death is 2.8 times higher, but you're seeing similar numbers in Hispanic or Latino persons as well. And even higher numbers in the American Indian, Alaskan Native and non-Hispanic person. So why African Americans right now? And can we apply this to other race groups in the future? 

Dr. Nathan Bryan  11:05  
Yes, you're correct. There are other ethnic groups that have the same or similar racial disparities. We chose African Americans, because these health disparities have been known for many decades. And now there's a fundamental mechanism of action that explains the health disparities in African Americans. It's in the female dysfunction and lack of nitric oxide production. So now we've got we work from the top down, we take epidemiological data, which really reveals the race, racial disparities, and the higher incidence of these things like high blood pressure, heart disease, diabetes. And so we have a mechanism of action that we can actually design drugs around to correct this underlying physiological problem that explains the racial disparities. So that's the reason we just have more data on fundamental mechanisms, whether it's physiological, whether it's lifestyle, and socio economic, or access to care, all of those have been really elucidated in the African American community. 

So I think I think it's also worth mentioning to that, you know, this isn't a repurposed drug, like many other drug companies are doing to throw it at COVID, we have a fundamental mechanism of action that's irrefutable and indisputable in terms of the science behind the increased risk of infection for COVID. And we're restoring this naturally produced molecule. So this isn't something we're looking to repurpose what we don't know the safety profile on. We know the safety profile of this. 

Cheng Ruan  12:33  
Yeah, wonderful. And so just to kind of clarify and bring it down into terms that people understand. Nitric oxide, so from what I understand is that, this nitric oxide component, which I believe was discovered in the late 80s. This nitric oxide, its job is to work on the lining of the blood vessels. And what happens is that as blood flows through the vessel, there's a shearing force, and there's inflammatory force that's on the lining of the blood vessels. And when that becomes compromised, people can develop clots, people can develop plaque and atherosclerosis onto that blood vessel, which eventually leads to cardiovascular death, like heart attacks and strokes and what not. Right. And so I find it interesting, because back in 2008, we already know that there's a racial disparity in African Americans that, that they suffered also 2.7 to 2.8 times higher cardiovascular death. So I find it very interesting that this 2.8x is very similar to COVID deaths. That's mirroring, right. Right. And so I don't think that's an accident. I do think that nitric oxide plays a humongous role in this. And I'm really glad that you know, we're finally looking at the target. But here's what I don't understand Dr. Bryan, and I think this is where you can really help me really capture this. So is it nature or is it nurture? Are different races born with this deficiency? Or is it that, there's cultural biases or socioeconomic biases? Is Is it both?

Dr. Nathan Bryan  14:20  
Well, I think it's both, they're clear. There's some genetic predispositions. So for example, there're two that stick out in the African American population. There's a single nucleotide polymorphism in an enzyme called glucose six phosphate dehydrogenase, we refer to it as a G6PD deficiency. African Americans have about a three times higher rate of G6PD deficiency than than the Caucasians. And that renders a lot of decreased nitric oxide production because of the metabolic byproducts that enyzyme that feed into making nitric oxide. The other one is an NADPH oxidase which makes more oxidative stress in the American population, which then further shuts down nitric oxide production. And then two when you have, you know, access to care, there's an issue with the African American population. So when African Americans get sick, they tend to wait longer to go to the doctor to their physician, whether it's they don't have access to care in that particular community, or there's distrust between the patient and the physician. So then they wait, and then the disease progresses to a point of really where it becomes critical. So it's both and it's also lifestyle. It's diet and lifestyle, you know, there's smokers, there's poor diet, and inflammatory diet, all contributes to this. So you may have the genetic predisposition. But if you do the things that epigenetically control the expression of those genes, its nurture and nature, both that really create the perfect storm for being susceptible to not just COVID, these patients also suffer the greatest in the seasonal flu, which were in the midst of the seasonal flu season. So this explains lack of nitric oxide explains everything we know about susceptibility to chronic disease, including COVID-19. 

Cheng Ruan  16:08  
Okay, so it's really a combination. And earlier, you said single nucleotide polymorphisms. So basically, these are genetic differences between people. So you know, obviously, there are smokers within all races, not just African Americans, as people with bad diets, in all races, all that contributes to decreased nitric oxide production in these races, but perhaps in the African American and maybe Latino American population, there are racial disparities and with with nitric oxide deficiency being much higher. So right now, you know, the focus is to first get some data on the African American population, see if possibly increasing nitric oxide in this population is able to affect outcomes. So can you define what we're trying to prove in the study? What are the actual outcomes?

Dr. Nathan Bryan  17:03  
Sure. So when we when we design clinical studies, we do a power analysis, and we have to have an end in mind, what we're looking for is to reduce the rate of hospitalization, admission into the intensive care unit in depth. So those are our primary endpoints, our secondary endpoints are looking at blood oxygen levels, changes in blood pressure, and also changes in temperature, how will your body's responding to the infection. And so when we do a power analysis, our goal was to reduce the rate of hospitalization by 25%. And when you do the biostatistics on that, we come up with we needed 840 patients. And so half of these patients are going to get a placebo, half of the patients are going to get an active, neither you as the physician at the clinical trial, nor the patients know if they're going to be getting the active or the placebo. So 50% randomized are going to get an active drug 50% randomized, you're going to get the placebo. And we're going to monitor these patients, we do remote monitoring through a telemedicine platform. And we can actually monitor their blood oxygen level. So I think that's a really critical important point. Because if you're diagnosed with COVID, especially for African American 50, to 85, there's fear involved. And so we're gonna hold your hand, and we're gonna call you two to three times a week to check on you, we can monitor you remotely, to make sure you're not rapidly progressing. And then, at the end of 30 days, you'll return back to the clinic if you're not in the hospital. And we'll combine the data once we have 840 patients that have completed the study. And I'm very confident that we'll see a profound impact on the active drug versus the placebo.

Cheng Ruan  18:44  
So this is great, because you know, the study's value here is not really just looking at the study drug, which is the NOviricid, it's also adding additional level of support through this monitoring and telemedicine platform so there's that an additional level of safety. Correct? 

Dr. Nathan Bryan  19:00  
Correct. 

Cheng Ruan  19:02  
And so, I think that whenever something's designed like this, we have to make sure that the intention is right. And the intention is here is to demonstrate this within the African American community.  Are their intentions look at other races or any other subgroups?

Dr. Nathan Bryan  19:22  
Well, yeah, no doubt we take in the African American, which is the most vulnerable, most susceptible population. If we can reverse the trend, and prevent the rapid progression of disease and hospitalization in the African American population, then it'll work just as well as in any other population. So there's some strategy to this because if we did, for example, if you took every single ethnic group and just did a broad clinical study in everybody and didn't, you know, single point the African American population to get that same power analysis would have to enroll about 80,000 to 90,000 patients Because as you know, some people get COVID, they're even asymptomatic. And they never get symptoms of the disease, other people, you know, will get pretty severe symptoms, and some may go to the hospital, some not. So but when you take this very known population, and we know the statistics from this population very well, now, after 10, 11 months of data. And so when you're exposed, you can plan it three to five days later, typically, people are going to develop symptoms, if they're highly susceptible, within five to seven days, they're going to rapidly progress and need to go into hospital. Once in the hospital, a couple days later, they're gonna be put on a vent, once you're on a ventilator, the prognosis is very poor. And within 10 to 12 days, the most susceptible people was to come to death from this disease. So we know without a doubt what the statistics looks like, and we can intervene and catch this early in the process and prevent that rapid progression of disease.

Cheng Ruan  20:54  
So yeah, so you know, so I guess the the main point here is looking at African American populations, statistically speaking, we'll do a test on 100 something patients instead of 80,000 to 90,000 patients faster to get this to market, is that correct?

Dr. Nathan Bryan  21:11  
That's correct. And it's part of the Coronavirus treatment acceleration program, which means we're not cutting corners, we're just basically putting this in front of the FDA. Safety's been established. This is an a phase 2B3A clinical trial, which we're looking at efficacy at this particular point.

Cheng Ruan  21:28  
Okay, great. And so a lot of people watching this are going to be wondering, can I get this drug right now is available right now? Or do we have to wait till the trial's done?

Dr. Nathan Bryan  21:38  
Now we have to wait till the trials done. I mean, this has to get the full the full rigor of FDA approved clinical trials, and then at the end of the study, we'll look at the data will submit a new drug application provided that the data is positive. And then we'll let the FDA do their job, review it for safety and efficacy. And then I'm confident we'll get approval, but now we can't sell this drug until there's an FDA approval.

Cheng Ruan  22:01  
Great. Now there are there downsides to taking this drug? Are there any side effects that we can potentially see,

Dr. Nathan Bryan  22:07  
Not at the dosing that we're recommending in this, in this clinical trial, you're taking one lozenge twice a day, 12 hours apart, the only toxicity of this would be a low blood drop in blood pressure. And we're monitoring the first 100 patients just to make sure they don't have an unsafe drop in blood pressure. And many drugs have what's called a first dose effect. And so we're just we're monitoring the first 100 patients for an hour after taking the first dose. And today, there's been no unsafe dropping in blood pressure. So there's really no known toxicities. This particular drug and this particular formulation, has versions of this have been on the market for 10 years with no issues of safety whatsoever.

Cheng Ruan  22:51  
Okay, so this is not necessarily something new. There's other versions of this that's been on the market for a long time. And haven't had any issues, correct?

Dr. Nathan Bryan  23:00  
That's correct. 

Cheng Ruan  23:01  
Okay. 

Dr. Nathan Bryan  23:02  
And so, it's almost like, you know, the, the analogy is, you know you can get naproxen, or Tylenol over the counter, you can also have a prescription version of that, like naproxen, or, or Tylenol 3 with an extra strength, or Motrin, or something like that. So it's following that same OTC which is basically just a safety issue. When you get drug approval, you're looking at both safety and efficacy. 

Cheng Ruan  23:27  
Gotcha, are there any drug-drug interactions that you perceive?

Dr. Nathan Bryan  23:32  
No, we haven't. And many of these patients are on multiple drugs, and mechanistically, we don't anticipate any interactions with any current medications, whether they're blood pressure medications, or antiviral medications, or even the standard of care they would be given if they were admitted to the hospital. So no known interactions, and we don't expect any.

Cheng Ruan  23:51  
Okay, that's wonderful. So we're looking at something that's been in different versions over the last 10 years, whether it's over-the-counter or not. And we're also looking at something that's relatively safe. And we're also looking at something that is reestablishes a defunct pathway in all humans, not just African Americans, but African Americans also are predisposed to it based on specific genotypes, as well, right. And so I think we're hitting all the all the marks there. And so this is why I'm excited to be participating in this trial, because there's different versions of this that I have used in my practice for various different things, from cardiovascular disease, to diabetes, to erectile dysfunction, and all sorts of different things. And so looking at this, specifically looking at COVID, I think that we are going to hit a home run and if we can get some data on this. And enroll, guys, just enroll at aaCOVIDstudy.com. And there's a questionnaire in there and you guys pick your location, whether it's Houston, whether it's Chicago, which, wherever it is, and then once you get on onto the site, and then just follow the directions and you're part of it. There's a pretty screening process on the web page. So make sure you go out there and sign up if you qualify. And so what if I want to thank you today for talking with me? I think this clears a lot, a lot of issues for a lot of people. If you have any questions, everyone just down in the comments below, throw them out there. We'll try to address them as much as possible. So thank you very much. Really appreciate your time sitting here and talk to us. And let's get this. Let's get this ball rolling.

Dr. Nathan Bryan  25:29  
Thank you, Dr. Ruan. Looking forward to no problem.