Oxford Haemodynamic Adaptation to Reduce Pulsatility Trial
Status:
Recruiting
Trial end date:
2022-12-01
Target enrollment:
Participant gender:
Summary
Chronic damage to small blood vessels deep in the brain is seen 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 almost half of patients with dementia. However, there is limited evidence for how
small vessel disease develops and no specific treatment. One potential explanation is that
greater pulsations in blood pressure are transmitted to the brain through stiff blood
vessels, resulting in increased pressure hitting the brain each time the heart beats and
reduced blood flow between heart beats.
Sildenafil is used to open up blood vessels (a vasodilator) in patients with erectile
difficulties or poor blood supply to the lungs. This trial will test sildenafil (50mg, thrice
daily) against placebo and a similar drug (cilostazol 100mg, twice daily) in 75 patients with
previous stroke or mini-stroke and small vessel disease, given in random order to every
participant for 3 weeks each. It will primarily assess changes in pulsations of blood flow to
the brain on each tablet, measured with an ultrasound scanner (transcranial ultrasound). To
understand why any changes occur, we will also measure the stiffness of arteries, the blood
pressure at the heart and how much blood vessels in the brain open up when participants
breathe air with added carbon dioxide (6%), using ultrasound in all participants and on MRI
brain scans in 30 patients.
This study will test whether a vasodilator used in other conditions with a good safety
profile can reduce pulsations in blood flow to the brain, to assess whether it is a good
candidate drug to reduce the progression of small vessel disease in future clinical trials.
This would be the first effective treatment for a condition associated with a very high
burden of disability.