NCT03855332

Oxford Haemodynamic Adaptation to Reduce Pulsatility Trial

Oxford Haemodynamic Adaptation to Reduce Pulsatility: Randomised, Placebo-controlled, Double-blind Crossover Trial of Effects of Sildenafil on Cerebral Arterial Pulsatility in Patients With Cryptogenic or Lacunar Stroke and Small Vessel Disease

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 75 (actual)
• Sponsor: University of Oxford · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Small Vessel Cerebrovascular Disease

Interventions

Type	Name	Description
DRUG	Sildenafil	See above
DRUG	Cilostazol	See above
DRUG	Placebo	Overencapsulated placebo

Timeline

• Start date: 2019-07-11
• Primary completion: 2022-12-06
• Completion: 2023-01-06
• First posted: 2019-02-26
• Last updated: 2025-11-19

Locations

1 site across 1 country: United Kingdom