SVDs@Target

An international consortium of mostly European investigators has launched a major collaborative research program to uncover mechanisms and pathways in different forms of small vessel disease.

Stroke and dementia rank among the most pressing health issues in Europe. Cerebral small vessel diseases (SVDs) have emerged as a central link between these two major co-morbidities. SVDs account for more than 30% of strokes and at least 40% of dementia cases. They encounter multiple distinct diseases that can be separated based on their underlying genetic defects, risk factors, and clinical presentations. Despite this profound impact on human health, there are no treatments with proven efficacy against SVDs.

The new network “Small vessel diseases in a mechanistic perspective: Targets for Intervention in Stroke and Dementia(SVDs@target)” is funded through the European Union’s Horizon 2020 research and innovation programme and brings together top scientists with a wide range of complementary expertise.

The project also includes 3 studies with stroke patients. They are:

ZOOM@SVDs, a high-resolution imaging study to look at vascular function and brain  damage

INVESTIGATE-SVDs, an imaging study to assess the blood/brain barrier and vascular function,

TREAT-SVDs, testing the effects of different blood pressure lowering agents on vascular function in patients with distinct SVDs

SVDs@target is a project consisting of preclinical work and clinical studies. With the three clinical studies involved in this project, we aim to increase our knowledge on small vessel diseases. The study designs were presented for the first time at the ESOC 2017 during the poster presentation.

Common features of all three clinical studies

We aim to include patients with sporadic small vessels disease clinically presenting with a lacunar stroke or vascular cognitive impairment. In addition, we will include CADASIL patients suffering from a genetic form of small vessel disease. In all our clinical studies, we will measure the function of the small blood vessels in the brain with a so called hypercapnic challenge. Participants will inhale medical grade air and a CO2-air-mixture. CO2 is a physiological stimulus for blood vessels to dilate. This will be measured using the BOLD MRI sequence.

Zoom@SVDs

We aim to advance our knowledge of why small vessel disease develops by using one of the strongest MRI scanners currently available.

Study type: case-control-study

Number of participants: 60 patients with sporadic small vessel disease, 20 CADASIL patients (genetic small vessel disease), 40 healthy controls (age- and sex-matched)

Study sites: Utrecht (NL) as coordinating centre; Munich (DE)
Study duration for each study participant: 8 days with a follow-up after 2 years
Status: recruiting
Flyer: available in German and in English
Further information will come soon.

INVESTIGATE-SVDs

We aim to use newly developed advanced MRI brain scans to measure how well the small blood vessels are working to prevent leakage of damaging inflammatory cells into the brain tissue and ensure enough blood gets to the brain when it is needed.

Study type: observational study

Number of participants: 45 patients with sporadic small vessel disease, 30 CADASIL patients (genetic small vessel disease)

Study sites: Edinburgh (UK) as coordinating centre; Maastricht (NL); Munich (DE)

Study duration for each study participant: 8 days with a telephone follow-up after 1 year (follow-up will not be included in Maastricht)

Status: Recruiting

Flyer: available in English, German and Dutch

TREAT-SVDs

(EffecTs of Amlodipine and other Blood PREssure Lowering Agents on Microvascular FuncTion in Small Vessel Diseases)

High blood pressure is one of the most important risk factors for developing small vessel disease but currently it is not clear which blood pressure lowering drugs are best at improving small blood vessel function. We propose that the function of the small microvessels in the brain can be influenced by medication.

Study type: clinical interventional trial comparing three blood pressure medications in small vessel disease

Number of participants: 75 patients with sporadic small vessel disease, 30 CADASIL patients (genetic small vessel disease)

Study sites: Munich (DE) as coordinating centre; Oxford (UK); Edinburgh (UK); Maastricht (NL); Utrecht (NL)

Study duration for each study participant: 14 weeks

Status: Recruiting

Flyer: available in English, German and Dutch


 

Meet SVDs@Target Investigators

Michael Stringer
Research Fellow in Magnetic Resonance Imaging and Image Analysis.
Centre for Clinical Brain Sciences, University of Edinburgh
Edinburgh Imaging and the UK Dementia Research Institute at the University of Edinburgh.

Why does this trial (Zoom/INVESTIGATE or TREAT) on small vessel diseases matter?

Investigate-SVDs recruits small vessel disease (SVD) patients to have advanced magnetic resonance imaging scans. SVD remains poorly understood, this study has great potential to further knowledge & ultimately improve outcomes for patients.

 What is it that you do in this project?

As a research fellow in medical physics at the University of Edinburgh I helped setup the magnetic resonance imaging protocol (guide to running the scans), liase with other sites and am heavily involved with analysis of the imaging data.

Why do you do it?

My research focuses on applying advanced imaging and mathematical methods to study disease. I enjoy applying these tools to study real world problems, and as a highly multidisciplinary area it provides a lot of variety – it is seldom dull.


Hilde van den Brink
PhD student
Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht

Why does this trial on small vessel diseases matter?

Amazing technical developments make it possible that we can now, for the first time in humans, study the small vessels themselves in Zoom@SVDs. I believe this is crucial in understanding small vessel disease and dementia.

What is it that you do in this project?

I am involved in most aspects of the trial, from patient recruitment, to patient visits, data analyses and all the behind the scenes (paper)work that is necessary to run a trial like this. However, of course good teamwork is key!

Why do you do it?

Because I truly believe that we first need to understand small vessel disease before we will better understand dementia. In the long run, I hope my work sparks ideas on possible treatments for this devastating disease.


Sébastien Foulquier

Senior Post-doctoral researcher
Pharmacology – Toxicology Dept, Maastricht University
CARIM – Cardiovascular Research Institute Maastricht
MH&NS – School for Mental Health and Neuroscience

Why does the research on small vessel diseases matter?

There is no way to prevent and treat this disease, while its prevalence is increasing with the population ageing. It is thus urgent to identify it early and to understand its mechanisms to delay/prevent its deleterious impact.

What is it that you do in this project?

We are studying the contribution of brain immune cells for the development of small vessel diseases in animals. We look at those cells and their interplay with brain small vessels and their impact on the cognitive function of the animals.

Why do you do it?

I strongly believe that immune cells can become dysfunctional when exposed to many cardiovascular risk factors and can contribute to the functional and structural remodeling of small vessels walls.


Tine Arts
PhD student
UMC Utrecht, Radiology department

Why does this trial (Zoom/INVESTIGATE or TREAT) on small vessel diseases matter?

It helps us understand the mechanisms driving small vessel diseases and related brain damage, which can lead to better treatment. The beauty is that these trials focus on various disease aspects, and complement each other knowledge-wise.

What is it that you do in this project?

I help collect the 7T data of the ZOOM trial and the 3T data of the TREAT trial. For the ZOOM trial, I analyse the data to obtain knowledge about the hemodynamics of the small cerebral vessels.

Why do you do it?

Small vessel disease is a major cause of stroke and dementia and so far no treatment has been found and it impacts the daily lives of many people worldwide. It is time we gain more understanding of this common disease.


Humberto Mestre MD, MSC
PhD student
Needergaard’s lab
University of Rochester Medical Center

Why does this research on small vessel diseases matter?

There is no cure for dementia. But half of patients have damage to the small blood vessels in their brain. Although there are no cures for dementia yet, it might be possible to prevent it in some patients by treating small vessel diseases.

What is it that you do in this project?

Blood vessels protect the brain from toxic compounds in the blood, but they also aid in the removal of waste produced by brain cells. We investigate how small vessel diseases impair these abilities and how this might contribute to dementia.

Why do you do it?

Dementia is a public health crisis. Incidence is expected to triple by 2050, and with the recent failure of several clinical trials, we need all hands on deck to solve this issue. Initiatives like this are vital in order to achieve this.


Laurien Onkenhout
PhD candidate
UMC Utrecht

Why does this trial (Zoom/INVESTIGATE or TREAT) on small vessel diseases matter?

Small vessel disease is common in the older population. It is also an important factor in vascular dementia. Studying the underlying mechanisms in the small vessels is key in tackling small vessel disease. I believe that TREAT@SVDs contributes to understanding the small vessels and their workings.

What is it that you do in this project?

I am one of the PhD’s on this project and together with our team I am involved in most aspects of the trial, from patient recruitment, to patient visits, data analyses and all the behind the scenes (paper)work that is necessary to run a trial like this.

Why do you do it?

I do this because it is my belief that, given the opportunity, one should always try to give back to the community. In this case by conducting research and via this way doing my small part in solving the large puzzle that might one day lead to the ability to solve (vascular) dementia. Understanding the disease is key.


Tushar Deshpande, PhD
Postdoc
Sorokin lab
Institute of Physiological Chemistry and Pathobiochemistry,
University of Muenster

Why does this research on small vessel diseases matter?

SVDs are inadequately recognized socioeconomic burdens. With the increasing life expectancy they will be one of the major future challenges. Unfortunately, not a single medicine has specifically been developed to target SVD and our current understanding of the disease is largely insufficient for identifying new therapeutic targets.

What is it that you do in this project?

I am investigating role of inflammation in the progression of SVDs. I am examining not only the mouse models of SVDs but also post mortem brain specimens of SVD patients for markers of inflammation and their correlation with the brain damage.

Why do you do it?

My fascination for neurological disorders and background training in neuropharmacology has propelled me to work on SVDs@target project. I believe that my research will help to better understand this disorder and pave a way for novel therapeutic strategies.