Cleveland Clinic Brain Study: A First-of-Kind Longitudinal Investigation

Podcast Transcript

Introduction: Neuro Pathways, a Cleveland Clinic podcast exploring the latest research discoveries and clinical advances in the fields of neurology, neurosurgery, neuro rehab, and psychiatry.

Glen Stevens, DO, PhD:

In Cleveland Clinic's landmark brain study aiming to pinpoint disease biomarkers before clinical symptoms present, I'm your host Glen Stevens, neurologist/neuro-oncologist in Cleveland Clinic, Neurological Institute. Joining me for today's conversations are Dr. Andre Machado and Dr. Imad Najm. Dr. Machado is a functional neurosurgeon and serves as the Co-PI on the Cleveland Clinic Brain Study as well as chairman of Cleveland Clinic's Neurological Institute. Dr. Najm is an epileptologist also serving as a Co-PI on the Cleveland Clinic Brain Study, and he's the director of Cleveland Clinic Charles Shor Epilepsy Center. Andre and Imad, welcome to Neuro Pathways.

Andre Machado, MD, PhD:

Thank you.

Glen Stevens, DO, PhD:

So I'm very hopeful and very excited about this study, not only for my patients, but also for my friends and family. I'm not sure if you're aware about my mother who had multiples sclerosis, and it's really the main reason that I decided to go into Medicine. And I think on a daily basis with my brain tumor patients, I hear the why and how long from my patients. How long have I had this? Why do I have it? And sadly, these are usually questions that we cannot answer, and I'm hopeful that this study will lead to answers and more early efficacious treatments. So let's start with an introduction to the research, and you can start to tell me simply, what is the brain study? Andre, do you want to start?

Andre Machado, MD, PhD:

Sure. The brain study is the first study of this scale, depth and detail to learn the underpinnings of neurological disease before neurological disease. The interest here is to study a very, very large cohort of normal individuals without neurological disease and follow them up as they age. We know that most will age healthy. Some unfortunately will age into neurological disease. And our objective is to understand the silent phase, what is happening to the brain, to the body, what's happening to health in the years that precede the first manifestation? That will be the most valuable time to develop new targets and come up with new interventions.

Glen Stevens, DO, PhD:

Excellent. Imad, what drove you to develop the study? And certainly you can add to anything that Andre has already discussed.

Imad Najm, MD:

Thank you, Glenn. As we know, the risk of being affected by a neurological disorder increases exponentially with age. With the annual incidence, that reaches its peak of approximately 15% per year in those of us who are 75 years and healthy. Now as neurologists, we know that the diagnosis of the neurological disorder during the later stages of life is made after the clinical symptoms are seen and sometimes even later. At that point, when we have the clinical symptoms or signs happening, studies showed that in patients, for example, with dementia, Parkinson disease, and epilepsy that there have been changes that preceded these clinical signs and symptoms at the molecular and cellular level.

Imad Najm, MD:

That's why the diagnosis is typically very late, and we all encounter the problem in dealing with this diagnosis after its onset. It's really difficult to stop, let alone to prevent these disorders from happening. So that's why we thought there is a need for an in-depth characterization of the brain and the body at various levels before the disease starts. And as Andre mentioned, during that silent phase with the main goal of looking at or identifying the fingerprints of the disease before the disease happens.

Glen Stevens, DO, PhD:

So as they say, it takes a village. And I think the scope of the project that you're looking at here really does take a village. What are the various clinical departments that will be involved with the study, the various services, and then maybe you can go into the breadth of the study, the numbers of patients you're looking at, and some of the criteria.

Imad Najm, MD:

If I answered it, is it okay?

Glen Stevens, DO, PhD:

Sure.

Imad Najm, MD:

We have multiple departments and specialists who are going to be involved in this study that will include neurologists, that will include various neurological subspecialists, such as Alzheimer's specialist, movement disorder specialist, stroke specialist, epileptologist, multiple sclerosis specialist, and then outside the neurological specialties, we have psychologists and psychiatrists involved. We have neuropsychologists, we do have neuroradiologists, ophthalmologists and geneticists with bioinformatic expertise.

Glen Stevens, DO, PhD:

And how many patients are we looking at?

Imad Najm, MD:

Our goal is to enroll up to 200,000 individuals over many years. And as a first phase, our goal would be to enroll around 10,000 individuals during the first five years of study.

Glen Stevens, DO, PhD:

So it sounds a lot like job security for both of you. So congratulations on that, but we're a large enterprise. Are you looking at centers outside of Cleveland, is Vegas going to be involved? Any of the other Florida?

Andre Machado, MD, PhD:

The study is named Cleveland Clinic Brain Study for a reason. We want to include and take advantage of the global organization that we are. And part of the opportunity is to increase the diversity. The study, for it to be successful, needs to be a representative sample of America. And the more inclusive we can be geographically and across races, ethnicities, the more informative this will be to developing new treatments down the line.

Glen Stevens, DO, PhD:

Excellent. Any exclusion criteria, Imad or Andre?

Andre Machado, MD, PhD:

The presence of neurological disease; we want to recruit normal volunteers. Then there will be other exclusion criteria, depending on things that we need to do. For example, if the person cannot have an MRI, we cannot enroll the person in the study. There will be some specifics, but I think the most important and perhaps counterintuitive thing to the public is that we are investigating people without neurological disease by the finish.

Glen Stevens, DO, PhD:

Now, I notice that within the criteria, adults who are 50 years of age plus with no known neurologic disease can do it or individuals greater than age 20 that have a first-degree relative with multiple sclerosis. Why did you choose multiple sclerosis as your neurologic disease for this study for younger patients?

Andre Machado, MD, PhD:

We're actually looking at all neurological diseases. This study is not aimed exclusively at multiple sclerosis, but one way of explaining this is that we do not want to miss the boat in multiple sclerosis and take advantage of the younger population that with family history may be at a higher risk and enroll these individuals when they're healthy. And also Glen, because we know that you are just a little over 30 and with your family history, we would like to be able to enroll you as well.

Glen Stevens, DO, PhD:

Well, that is true. It's too bad that people can't see me because then they would obviously easily realize that. About anything else to add to that in terms of criteria for patients or I could just ask you, how's it going? Have you actually started to enroll patients?

Imad Najm, MD:

Yes. We actually enrolled our first patient.

Glen Stevens, DO, PhD:

Congratulations.

Imad Najm, MD:

In mid January. For the last week or so, we've got more than a couple thousand individuals who signed up to be enrolled in this study. And we are now scheduled for almost every business day for the month of January and February.

Glen Stevens, DO, PhD:

Actually. I'm not surprised about the excitement when I was coming over to do the podcast, I was talking to my nurse and she said that she's looking into the study and wants to do it. So there's clearly a lot of interest within the organization and even outside the organization as there should be.

Imad Najm, MD:

There is another detail of about this study that is very important, which is the individuals who we are trying to recruit, they do not need to be necessarily patients of Cleveland Clinic. We aim to enroll patients or individuals from various backgrounds and that the final picture that we have should mirror the society that we live in as in United States.

Glen Stevens, DO, PhD:

You always learn the first few patients, you put on a study of how you should be doing it differently. So I'm sure that will evolve as you move through. Anything that you've learned already with the first patient that, boy; this is going to take a lot longer than we thought, or boy, it went nice and smooth.

Andre Machado, MD, PhD:

We learned something really important this morning. We heard Theresa, our first patient, speak about this study, and she outdid Dr. Najm and I by a lot. She understood very much the purpose of this study, why we're doing this, and she made the case for everyone else to participate.

Glen Stevens, DO, PhD:

I think that it just has such far reaching implications for all of us. And even though I'm only 30, I'm rapidly getting older, so our time is coming one in six, right? So I think that this is very important information that we all need.

Andre Machado, MD, PhD:

It is and I think that in one way looking at this study, is thinking about the next generation. We today benefit from great advancements of medicine that were developed by our predecessors, by our ancestors. And they dedicated their time, effort and resources for us to have better health. I think that this is an opportunity given the technological advancements that we now have, for us to do this and provide better neurological outcomes for our next generations. Do this not only for ourselves, but thinking of our kids and grandkids as the results may take some time to come through.

Glen Stevens, DO, PhD:

I think one of the other unintended benefits within the institution is that as set institutions get large, it's harder to interact with other departments and know everybody that's around. So the nice thing about this is it adds to the collegiality, it allows people to do studies together, and who knows what we'll develop from it. I think that things will spring forward that we had no idea just because we put everybody together in a multidisciplinary approach.

Andre Machado, MD, PhD:

I think you're completely right. This study is unusual for a study. We are not making a predefined hypothesis here. We have some thoughts on what we think we will learn, but we have the full expectation that we will learn things that none of us are expecting now, and that folks outside of our field may find ways to analyze this data that we today don't know, and that the next generation will have an opportunity to look at this data. In other ways that today, we don't quite yet know how to do.

Glen Stevens, DO, PhD:

Exactly. So since you brought it up, I'll just ask you short term, long term, do you have some preset thoughts as to what you might find or do you not want to jump into the pool at this point on that?

Andre Machado, MD, PhD:

I find that predictions are difficult to make, especially about the future, and I'll let them do that.

Glen Stevens, DO, PhD:

Imad, do you feel brave enough?

Imad Najm, MD:

Yes. Well, Dr. Machado asked me to do it, so I'm going to try my best to predict the future, but I hope in 10 years, you would not come after me. No, I think, if we want to think about short term versus long term, I think in the short term, we should be able to identify surrogate biomarkers in the silent phase to predict the onset of various neurological problems, and these biomarkers, because of the degree of hypercharacterization that we are getting our individuals to go through, could be the blood biomarkers, like inflammatory biomarkers for example, or could be at the level of the structure of the brain, looking at MRIs or it could be at the neurophysiological level or it could be at the psychological, neuropsychological, cognitive level.

Imad Najm, MD:

So we think there may be in a short term, some not causative biomarkers, but maybe biomarkers in the silent phase to tell us that this person is at risk of developing a dementia, Parkinson's, stroke, multiple sclerosis or epilepsy amongst others. Now in the mid to long term part of the study, we think here there will be the more exciting findings for us. And this will be the phase of identifying actionable biomarkers, targets for treatment. And that will be here in the starting new phase, in the phase of designing medications or biological interventions to target these various causative biomarkers that we are identifying.

Imad Najm, MD:

And there is an emerging field that we think will be using or will be taken advantage of, which is we may be able to identify pathways, genetic pathways or the molecular pathways that will be causative for a type of Alzheimer's for example, or in the silent phase of development of epilepsy that we can repurpose already existing medications for the treatment of these at risk individuals leading to the dream of the study and the long-term goal of this study, which is to find a cure for these neurological disorders.

Glen Stevens, DO, PhD:

Well, I am wondering-

Imad Najm, MD:

I think you did very well. I-

Andre Machado, MD, PhD:

Okay, good. As we were saying before, we want to recruit a very good representation of all of us, of the population of the United States. We ask that all of you listeners to please volunteer yourselves for this study, but equally important to talk to your community and circle of friends and family, bring them into this study. By bringing your friends and your loved ones, you will increase your impact and multiply your effect and help us lead this into the future.

Glen Stevens, DO, PhD:

Good.

Andre Machado, MD, PhD:

For folks to join the Cleveland Clinic in the future and participate in the analysis of this data. In one way, I don't know if Imad and I will be discovering anything from this. I hope we will, but I think we have a very, very, very high chance that folks that will be our successors discover wonderful things. You always have to start somewhere, right? We may be just doing that.

Glen Stevens, DO, PhD:

Well, that's a great thing, right? This is going to leave the cupboard full.

Conclusion: This concludes this episode of Neuro Pathways. You can find additional podcast episodes on our website, clevelandclinic.org/neuropodcast, or subscribe to the podcast on iTunes, Google Play, Spotify, or wherever you get your podcasts. And don't forget, you can access real-time updates from experts in Cleveland Clinic's Neurological Institute on our Consult QD website. That's consultqd.clevelandclinic.org/neuro, or follow us on Twitter @CleClinicMD, all one word. And thank you for listening.