ISTAART RELAY Podcast – Clinical Trials Advancement and Methods PIA

Narrator:

Hello, and welcome to season seven of the Dementia Researcher "ISTAART Relay" podcast. In this series, members of the ISTAART's professional interest areas interview each other about their PIAs and the hot topics in their fields. Each guest then becomes the next episode's host, passing the conversation along from one researcher to the next. We are releasing one episode a day in the run up to the Alzheimer's Association International Conference, this year in London and online, showcasing the work of the ISTAART PIAs. Thank you for listening.

Dr Sindhuja T Govindarajan:

Hello and thanks for tuning in. I'm Dr Sindhuja T Govindarajan. I'm an Alzheimer's Association research fellow and postdoctoral researcher at the University of Pennsylvania. And over the summer, I'll be transitioning into a new role as an assistant professor at the Karolinska Institute. I also serve as the outgoing chair on the Professional Interest Area for Elevating Early Career Researchers, it's shortened as PEERs PIA, and this is within the ISTAART. Today, I'm delighted to be talking with Dr Carla Abdelnour from the Clinical Trials Advancement and Methods PIA. Hi, Carla, welcome to the show.

Dr Carla Abdelnour:

Hi, Sindhuja.

Dr Sindhuja T Govindarajan:

To kick things off, could you introduce yourself to our listeners and tell us a little bit about your current work and research focus?

Dr Carla Abdelnour:

Of course. My name is Dr Carla Abdelnour, I'm a clinician scientist, and I work in Barcelona, Spain at the Hospital de la Santa Creu I Sant Pau in the neurology department in the memory unit. My work focuses on studying mixed neurodegenerative diseases of ageing, particularly Lewy body disease with Alzheimer's disease mixed pathology. And what I want to do with my research is to try to understand how these proteinopathy interact to develop better tools for diagnosis and also for treatments of our patients.

Dr Sindhuja T Govindarajan:

That's great. That's such a massive space at the intersection of two very important questions. How did you first get involved in this area of research?

Dr Carla Abdelnour:

Well, that's a great question, Sindhuja. I started working on this approximately 10 years ago, when I started my PhD. I developed my PhD on dementia with Lewy bodies and Alzheimer's disease mixed pathology. I was studying patients with dementia with Lewy bodies who had Alzheimer's disease profiles in CSF. So, I studied different aspects of this mixed pathology, in particular how these patients progress over time, because they have faster progression, as our studies have also shown. We studied how the presence of AD pathology in DLB influenced clinical presentation and atrophy patterns. All of that work was done in collaboration with the European Dementia with Lewy Body Consortium, which I am very grateful to for their help with my PhD. Then I moved to the US to do my postdoctoral fellowship with Kathleen Poston at Stanford University.

There, I was able to include Parkinson's disease patients with cognitive impairment who also had Alzheimer's disease biomarkers. Then I had the full Lewy body disease spectrum to study and could understand the differences, and how the presence of Alzheimer's disease pathology influences cognition, disease progression in general, function, global cognition and so on. I also tried to study novel biomarkers, in this case plasma markers, and how to interpret them in the setting of mixed pathologies. It has been great working in this field for all these 10 years, because I have been seeing the growth in awareness of co pathologies, which is great. I am excited to see how many people are now interested in this field. I started working on it in my PhD. It was a great opportunity.

At that time, I was working at Fundació ACE as a neurologist, and I got the opportunity to join the European Dementia with Lewy Body Consortium and work on our dementia with Lewy bodies cohort. That is how I got into this field. To be fair, when I finished my residency as a neurologist, I was interested in stroke and also movement disorders. Then I got into the memory unit, and I fell in love with our patients who have cognitive impairment, because it is so interesting. Our memory and our behaviour are what make us human. Since I started neurology, what I wanted to do was understand our brain and how the brain works. So, understanding behaviour and cognition is a great way to do that.

When I got the opportunity to work on dementia with Lewy bodies, it was pure luck, but I was very lucky because I was able to combine my passion for movement disorders, so Parkinson's disease, but also cognition. I have always thought that sometimes we make these different fields a little bit arbitrary. In the end, they are all neurodegenerative diseases, and the patients are very similar. Sometimes, because of how these diseases have been described, we separate them, but they are more similar than we think. So, I am very happy to be kind of in both fields, because that gives me the opportunity to gain experience from one field and move the information to the other, and have a different perspective.

Dr Sindhuja T Govindarajan:

I think we're kindred spirits in that. I did my PhD with a different field of neurodegeneration and moved to the field of ageing. I worked on multiple sclerosis before and there are a lot of commonalities in terms of how the brain is affected. And I could see like the spark in your face when you're talking about how complex the brain is. I agree with you that a lot of the presentations perhaps even are similar across a diverse spectrum of diseases. But exactly how we study them is quite different, right? So, for example, I'm representing the PEERs PIA today, but my area of research is neuroimaging, mainly MRI focused. And so, we're looking at how the pathological mechanisms manifest, how can we study them in vivo, you know, before sometimes when cognitive impairment is present sometimes during the process along the continuum.

In terms of your specific research areas, am I right in understanding that you're focusing more on the plasma markers and as such the biofluid markers and cognition? Can you tell us about the methodologies you use for your research?

Dr Carla Abdelnour:

Yes, of course. I have been analysing biofluid biomarkers, mainly CSF. More recently, I have also been studying plasma markers. During my PhD, I also studied MRI for atrophy patterns. But I think my goal is to work more on fluid biomarkers, because they are some of the best measures to understand different proteinopathies and different processes. That is why I am very excited that we are now able to identify alpha synuclein in CSF. I remember doing my PhD when we were not able to do that. That is fairly recent. I remember reading papers that ended by saying, well, what we need is an alpha synuclein biomarker, and now we have it.

That has changed our understanding of these diseases and the awareness, as I mentioned before, of the frequency of mixed pathologies and all the implications that will have for our patients and the treatments that we decide for them. So, I think I am more inclined, or I guess biased, towards fluid markers, because we can identify different proteins that reflect the proteinopathies, but also the pathophysiological processes that might indicate disease progression. I am interested in trying to find biomarkers for monitoring patients, or seeing if we are able to identify markers, for example, for responses to treatment, or for better prognosis or prediction. I guess biofluid markers are very good for that. But I am happy to incorporate other markers too, from imaging.

In particular, I will be very happy when we have a PET tracer for synuclein. That would be great, to see alpha synuclein in the brain. I think that will be really exciting.

Dr Sindhuja T Govindarajan:

That's great. One cannot argue with the specificity that comes from biofluid markers and how complementary they interact with other biomarkers as well, it's great to hear. So, in your opinion, do you think the more recent advancements or discoveries that you're so excited about are adequately incorporated in clinical trials? Like what would you want if you had a magic genie or a magic wand, what wish would you want to incorporate in clinical trials to fix a current problem?

Dr Sindhuja T Govindarajan:

I think that is a great question. One of the things that I am very excited about is incorporating the identification of different proteinopathies in clinical trials, either for inclusion, exclusion, or stratification. I think maybe we can start with stratification. There is this question about what happens when a patient with Alzheimer's disease, for example, receives a treatment for amyloid or tau but also has alpha synuclein. Does that person respond in a similar way to a person who does not have alpha synuclein, or Lewy bodies? I think this is a fair question, and I definitely would love to see more clinical trials trying to answer it as a secondary outcome or exploratory outcome. I understand the difficulties, though, because right now alpha synuclein is available only in CSF. Not all clinical trials have CSF as an inclusion criterion.

Sometimes you can only have PET, or amyloid or tau inclusion criteria. And not all clinical trials in Alzheimer's disease require biomarker confirmation either, so that is another thing. But I understand that it is not easy. Even in a subgroup of patients, clinical trials could try to answer that. There are some great ongoing clinical trials happening in that space, so I am very excited.

Dr Sindhuja T Govindarajan:

That's great. Your excitement for the research topic and for the future horizon is very obvious from the way you can talk about this. That's been really helpful to set the stage for what I want to talk about next, which is the work of your PIA with the Clinical Trials Advancement and Methods PIA, can I call it the CTAM PIA?

Dr Carla Abdelnour:

Yes.

Dr Sindhuja T Govindarajan:

Okay, great. So clearly, it's a massive interdisciplinary effort with converging disease spectrums, with converging proteinopathies, diverging as well, which is what makes it very fascinating. So how does your PIA organise itself with the different experts from statisticians to clinicians? How are you organising, how do you bring this work together within the PIA?

Dr Carla Abdelnour:

Well, I think that's a very good question. In our PIA we have collaborative environment and we're very open to any topic or idea that somebody might have. And we always try to encourage people and help them and support them in moving those ideas forward because usually they are within the objectives of the PIA. What our PIA wants to do is we want to develop better tools for synuclein clinical trials. And also, we have a second objective that has to do with the education of people about the design of clinical trials.

So yes, you're right, we're very interdisciplinary PIA and I think that's a strength because we can learn from different perspective, and, yes, so any idea that people have and any of the members, I invite them to collaborate, if you have any idea about something that you want to develop either a webinar or a different activity or a paper, just reach out to us where we will support you with your idea and probably put you in contact with people that will help you.

Dr Sindhuja T Govindarajan:

Yes. Our PIA is on clinical trials and methods. The methods part is one of the very interesting ones, because what we want to do is develop novel methods, or identify methods, for clinical trials for Alzheimer's disease and related disorders. The second objective is to educate people about how to conduct clinical trials. What are the best methodologies if you have an idea for a clinical trial? I find that fascinating. There have been a lot of webinars and different activities that the PIA has developed over the years to support people in this regard. Clinical trials are very difficult to manage and perform, but I think with the right support, they can be done. So again, if people are interested in learning more, just reach out to us.

Dr Carla Abdelnour:

Yes. So, our PIA is on clinical trials and methods. And the methods part is, I think, one of the very interesting ones because what we want to do is try to develop novel methods or identify methods for the clinical trials for Alzheimer's disease and related disorders. And the second objective is to educate people about the, how to conduct clinical trials? What are the best methodologies that you have an idea for a clinical trial? Which I found fascinating and, there have been a lot of webinars and different activities that the PIA has developed over the years to support people in this regard. Clinical trials are very difficult to, to manage and to perform. But I think with the right support that can be done. So again, if people are interested in learning more, just reach out to us.

Dr Sindhuja T Govindarajan:

Yes, I love that question. I got involved in 2020, during the pandemic. I remember receiving the email invitation and thinking, oh my god, which is such a great opportunity. During the pandemic, I was working in Fundació ACE as a neurologist, and I was heavily involved in the clinical trial unit. I was actually the deputy head of the clinical trial unit, and I was coordinating several clinical trials and more than 100 participants in clinical trials. During the pandemic, the question was, oh my god, how are we going to cover clinical trials in this situation? All these protocols, all these visits, what are we going to do? We had to adapt very quickly. I thought it would be a great opportunity to reach out to people from different parts of the world and understand how they were going to manage that situation.

It was a great opportunity in that regard. I learned a lot from my colleagues around the world, and since then I have been very involved in the PIA.

Dr Carla Abdelnour:

Yes, I love that question. So, I got involved in 2020. It was during the pandemic. I remember when I received it, that email of invitation, and I thought, oh my god, that's such a great opportunity because during the pandemic I was working in Fundació ACE as neurologist and I was heavily involved in the clinical trial unit. I was actually the deputy head of the clinical trial unit, and I was coordinating several clinical trials and more than 100 participants in clinical trial. And during the pandemic what happened was that we had that question, oh my god, how are we going to cover clinical trials in this situation, right? All these protocols of these visits, what are we going to do? We have to adapt really quickly to all of that.

So, I thought that that will be a great opportunity to reach out to people from different parts of the world and understand how they were going to manage that situation. It was a great opportunity in that regard. I learned a lot from my colleagues around the world or how they were managing that. Where after that it was a great opportunity also for networking. I have been always interested in clinical trials because I'm a clinician, and I want also been able to develop better treatments for my patients, and clinical trials are the best way to do that, right? It helps me also being up to date on the treatments that are being developed in the pipelines of the different neuroactive diseases.

So yes, I think clinical trials are very helpful, and as a researcher, it also has taught me about what is the best way to develop a protocol for a research. So, if you are a researcher doing an observational study or you have an idea of an observational study, learn about clinical trials because that will be a great foundation, that is the gold standard, I would say, for developing protocol for any research. It's the highest level of scientific evidence, so learning about clinical trials is actually very helpful for your career. So then, that was what brought me to the CTMP and has been an amazing journey.

Dr Sindhuja T Govindarajan:

Yes, of course. We are in the process of updating our executive committee. Currently, the vice chair, Rema Raman, is the chair of our PIA. She has done amazing work during the last two years, and I am very grateful for her leadership. This year I will be the new chair of the PIA, and we are waiting for the elections because we recently had elections and will have our new executive committee team. I am looking forward to meeting them either in person or virtually. We can have a virtual coffee if needed. We are in the process of building the new executive committee, but we have had an amazing committee this year and over the past period. We have three working groups. We have a working group on Lewy body trials, which I work on in collaboration with the Lewy Body Dementia PIA.

We also have another working group on diverse representation across the workflow, and another one about remote assessments in clinical trials. We have several working groups, and if people want to be involved in any of them, please reach out. I will be happy to talk with you about your ideas and how to get involved more actively.

Dr Carla Abdelnour:

Yes, of course. So, we're in the process of updating our executive committee, and currently the vice chair, Rema Raman, is the chair of our PIA, she's been an amazing work during the last two years and I'm very grateful for her leadership. And this year I will even a new chair of the PIA and we are waiting for the elections because we have elections just recently and we will have our new EC team, which I'm, I'm looking forward to meet them either in person or virtually, we'll have a virtual coffee if needed. So yes, we're in the process of building the new EC, but we have had an amazing EC this year and the past period and we have three working groups. And so, we have a working group on Lewy body trials that I work on in collaboration with the Lewy body dementia PIA.

We also have another working group on diverse representation across the flow, and we have another one about remote assessments in clinical trials. So, we have several working groups and if people want to be involved in any of these working groups of have other ideas, please reach out, and I'll be happy to talk with you about your ideas and how to get involved more actively.

Dr Sindhuja T Govindarajan:

Yes. During AAIC, I encourage people to come to the PIA. There is going to be an amazing panel discussion on global representation in clinical trials. This is something that we have been discussing a lot during the past three years. Rema Raman and Jorge Llibre are leading that effort with the working group, and that is going to launch at AAIC. So please come to our PIA Day. I think it is going to be an amazing discussion. In addition to that, we have a Featured Research Session on a similar topic around representation, led also by Rema. I do not recall the exact details, because I have not checked the programme in detail just yet, but we are going to have a Featured Research Session on clinical trials from the CTAM PIA. I will be in London, so if you have questions about how to get involved more actively, please come and talk to me.

We are always asking for members' input or ideas. I think we are a very open PIA. One of the things that we want to do next year, in addition to continuing the work from the previous executive committee, is to increase member engagement, particularly among early career members who might be interested in clinical trial design or methods. So, reach out to me. I will be happy to give you my contact details, and then we can have a more personal discussion about your ideas or how to get involved.

Dr Carla Abdelnour:

Yes. So, during AAIC, I encourage people to come to the PIA. There is going to be an amazing discussion, a panel discussion on global representation in clinical trials. This is something that we have been discussing a lot during the past three years. Rema and Jorge Libre, Rema Raman and Jorge Libre are leading that effort with the working group and that is going to be a launch at the AAIC. And so, please come to our PIA Day. I think it's going to be an amazing discussion. And in addition to that, we have a Featured Research Session on the similar topic on representation that is led also by Rema. I don't recall the exact details but just reach out because I haven't checked the programme in detail just yet, but we're going to have a Featured Research Session on clinical trials from the CTAM PIA.

And I'll be in London, so, if you have questions about how to get involved more actively, we're always asking for members input or ideas. We, I think we're very open PIA, and one of the things that we want to do for next year, in addition to continue the work from the previous EC is to continue the increase of the engagement of the members, in particularly, the early career members that might be interested in clinical trial design or methods. So yes, reach out to me, I'll be happy to, to give you my contact then we have, can have more personal discussion about your ideas or how to get involved.

Dr Sindhuja T Govindarajan:

Great. I particularly like your mention of early career researchers because that's the objective of my PIA, which is PEERs PIA, that I represent. In terms of easier involvement, you also have an EC position for early career researchers, right?

Dr Carla Abdelnour:

Yes, that's correct.

Dr Sindhuja T Govindarajan:

Can you-

Dr Sindhuja T Govindarajan:

Yes. In the past, the early career researchers have been involved in helping us with the year in review webinar. That year, actually, we used to do two segments within one webinar, because we wanted to talk about pharmacological trials and nonpharmacological trials. As you can imagine, Sindhuja, that is a lot of work. But people have done amazing work. I remember last time it was Erina who took on the pharmacological trials, and I am very sorry because I do not remember the other person, but I think it was an amazing summary of what had happened. Clinical trials are such a big field. There are a lot of clinical trials happening within one year. I think it is a good opportunity to stay up to date with what is happening, and I think we are going to continue to do that.

In addition, I think we might also want to consider discussing novel methodologies, not only focusing on clinical trials from the pharmacological or nonpharmacological side but also asking what new methodologies people are developing for designing clinical trials.

Dr Sindhuja T Govindarajan:

Although the elections are done for this year, can you tell us a little bit about what kind of activities have those ECR executive committee members gotten involved in in the past?

Dr Carla Abdelnour:

Yes, I think that is a very good question. Clinical trials are organised in different phases, and each phase has a main objective. You identify your outcomes depending on the phase of your study. For example, if you are conducting a phase two trial where you want to study safety and tolerability, your outcomes will have to reflect that, although you can incorporate cognition, function or other aspects that interest you as secondary outcomes, and biomarker changes as exploratory markers. When you have a project or a research question, you design your methods to answer that specific question. You design your experiment to answer that question, and you identify the outcomes that you have to measure. What I think might be similar between the two approaches is how to develop the protocol.

For example, you have to identify the exclusion and inclusion criteria for the subjects. You have to identify all the outcome measures and describe them. You have to calculate your sample size, to know whether you have enough people involved, or samples, or whatever you need to answer your research question. That is very important in both clinical trials and research studies. Having all that prepared beforehand, before doing the actual study, is very helpful. So, I think the way clinical trials are structured is translatable, for the most part, to observational studies. It has a similar to do list when you are designing an observational study.

Dr Sindhuja T Govindarajan:

So, in what ways do you think the methodologies or techniques that you use for clinical trials different from what's used in research studies? Like what are the challenges that one might not know about if they've only been exposed to, you know, research prospective studies like that?

Dr Carla Abdelnour:

Yes, I think that's a very good question. I guess, well, the clinical trials since they are organising different phases and each phase has some main objective, you will identify your outcomes depending on the phase that your studies. So for example, if you are conducting a phase two trial where you want to study safety and tolerability, your outcomes will have to reflect that, although you can incorporate as a secondary outcomes, cognition function or other aspects that your interest, for example, biomarker changes as an exploratory markers, et cetera. Now, when you have a project or a research question, you will be designing your methods for answering that specific question, right?

You are going to design your experiment to answer that question, and you will identify what are the outcomes that I have to measure to answer my research question. What I think might be similar between two approaches is how to develop the protocol, for example, you will have to identify what are the exclusion and inclusion criteria for their subjects. You are going to have to identify all the outcome measures and describe them. You have to calculate your sample size to know you have enough people involved or samples or X to answer your research question, which is very important in both clinical trials and research studies. And so, I think having all that prepared beforehand, before doing the actual study is really helpful.

So, I think the way that clinical trials are structure is translatable the most part to observational studies, has a similar to do list. This is when you are designing an observational study.

Dr Sindhuja T Govindarajan:

Clinical trial design is very complex and interdisciplinary it looks like. You previously mentioned what you would like to see ideally in a new clinical trial with the incorporation of like a magic wish of PET alpha-synuclein. But in terms of recent studies that have shown success, is there a particular study that sounds very exciting to you, very promising that you want to see more of?

Dr Carla Abdelnour:

Such a good question. So, do you mean research study or a clinical trial in particular?

Dr Sindhuja T Govindarajan:

Yes. I went to AD/PD recently in Copenhagen, and they presented a clinical trial that is going to investigate a treatment in people with Lewy body disease. I am very excited about that clinical trial. It is a phase two trial. It has also been done in collaboration with the Lewy Body Dementia Association, and that has been an effort led by Charles Shih from Stanford and Doug Galasko from UCSD. I am really happy to see that because I need to know whether these treatments also work in the population with that clinical phenotype, for example Lewy body disease, but with the presence of amyloid data.

Dr Carla Abdelnour:

A clinical trial?

Dr Sindhuja T Govindarajan:

I mean a clinical trial in specific, yeah.

Dr Carla Abdelnour:

Yes, yes. So, I went to ADPD recently in Copenhagen and they presented a clinical trial that is going to investigate a treatment in people with Lewy body. So yes, I'm very excited about that clinical trial. It is a phase two trial. It has been done also collaboration with the Lewy Body Dementia Association and, and that has been an effort that has been led by Charles Shih from Stanford and Doug Galasko from UCSD. So, I'm very, yes, really happy to see that. because I just, I just, I need to know, I need to know if this, this, these treatments also work in the population of that clinical phenotype that is for example Lewy body disease but have the presence of amyloid data.

Dr Sindhuja T Govindarajan:

Thank you for sharing that. What advice would you have for someone who is new to ISTAART or Alzheimer's Association in general in this field of work? How do you think it has helped you to be involved outside of research advancements alone?

Dr Carla Abdelnour:

Yes. I think that's a very important question. I will say reach out to members from different PIAs from your main interest. I think people are very open to extend their experience, so, if you reach out to people and ask them about their experiences, if you are interested in getting involved more actively in any of the activities, just reach out to people. Also, you can reach out to the Alzheimer's Association and the PIA directly. I think their leadership team is amazing. They, they're doing an amazing job helping us to build this network of collaborators across the world. So, you have any questions, I think that's also a great resource.

There is a lot of information on the PIA website about the different PIAs if you want to check that also, because there are a lot of opportunities and you might have different interests, not only on one field, but different fields. And you can definitely be a member of several PIAs at the same time and different working fields too. I will also say that it's an amazing opportunity to meet people, to discuss ideas, and at the end, to move the field forward, Sindhuja, because this is such a complex problem. We want to develop better diagnostic tools, a better treatments for our patients. And we're not going to do that alone, we need a big team, a global team. And the Alzheimer's Association with the PIAs are doing that. So, I'm very happy to be part of the PIA, and I will say that if you interest, just reach out.

We need more people working on this problems, more people trying to answer these questions. So yes, just come onboard and help us to end dementia.

Dr Sindhuja T Govindarajan:

Well said, we cannot do this alone, we have to work together on that. I think that is a fantastic wrap up for the podcast so far. Thank you all for listening. This is the last show in the season for 2026. ISTAART PIAs are a great way, like Carla mentioned, to expand your network, find new collaborators, and learn more about Alzheimer's and dementia field in general. We hope that these podcasts have inspired you to get involved and you can find the profiles on myself and our wonderful guest, Carla, and information on how to become involved in the ISTAART on our website at dementiaresearcher.nihr.ac.uk, and also at www.alz.org/istaart, or, for simpler terms, Google ISTAART and it'll take you there.

We're looking forward to seeing you at the AAIC conference, so, if you haven't already registered, visit alz.org for more information and come find us and say hello. Thank you. Bye.

Dr Carla Abdelnour:

Thank you. Bye.

Narrator:

You have been listening to the "Relay" podcast, delivered as a collaboration between Dementia Researcher and ISTAART. This podcast is made at University College London with generous funding from the NIHR, Race Against Dementia, Alzheimer's Association, Alzheimer's Research UK, and the Alzheimer's Society. Please like and subscribe and share your thoughts in the comments.