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Researchers in our Centre for the Prevention of Stroke and Dementia have begun a clinical trial to assess whether the drug sildenafil could improve blood flow to the brain.

Model brain © Robina Weermeijer/Unsplash

Chronic damage to small blood vessels deep in the brain is found in half of patients over the age of 60 and almost all patients over the age of 80, and is responsible for up to a third of strokes and around 40 per cent of dementia.​

Dr Alastair Webb, of the Wolfson Centre for Prevention of Stroke and Dementia, is leading the study. He explained: 'There is limited evidence for how this small vessel disease develops and no specific treatment. We aim to test whether sildenafil has the potential to reduce small vessel damage.'

Potential explanations for how small vessel disease develops include: a greater change in blood pressure with each beat of the heart (pulsatility), which hits the brain with increased force with each beat; or a reduced ability of the blood vessels in the brain to adapt to changes in the environment, also known as their reactivity.

Sildenafil is currently used to open up blood vessels in patients with erectile difficulties or poor blood supply to​ the lungs.

This trial, which is supported by the NIHR Oxford Biomedical Research Centre and the Wellcome Trust, will test sildenafil against a placebo tablet and against a similar drug called cilostazol in 75 patients​ who have had a stroke or mini-stroke previously and who also have evidence of injury to their small blood vessels on a brain scan.

'We will compare three weeks of treatment with sildenafil, cilostazol and the placebo to assess whether they improve pulsations in blood flow or reactivity of blood vessels in the brain,' Dr Webb said.

This will be measured using an ultrasound scanner whilst participants breathe air or a mixture of air and six percent carbon dioxide. To understand why any changes occur, the team will also measure the stiffness of arteries, the blood pressure at the heart and the body’s blood pressure control mechanisms.

Finally, 30 participants will have similar tests whilst undergoing an MRI brain scan to test changes in blood flow to the brain in even greater detail.​

This study will test whether these ‘vasodilating’ medications – drugs that widen the blood vessels – are good candidates to reduce the progression of small vessel disease in future clinical trials, and so reduce the risk of stroke and dementia.

'This would be the first specific treatment for this very common condition that is responsible for a significant amount of disability,' Dr Webb explained.

The trial is expected to last around two years.