Oxford Haemodynamic Adaptation to Reduce Pulsatility Trial (OxHARP)
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|ClinicalTrials.gov Identifier: NCT03855332|
Recruitment Status : Recruiting
First Posted : February 26, 2019
Last Update Posted : August 2, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Small Vessel Cerebrovascular Disease||Drug: Sildenafil Drug: Cilostazol Drug: Placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||75 participants|
|Intervention Model:||Crossover Assignment|
|Intervention Model Description:||Randomised, double-blind, placebo and active controlled, crossover design|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||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|
|Actual Study Start Date :||July 11, 2019|
|Estimated Primary Completion Date :||December 2021|
|Estimated Study Completion Date :||December 2021|
Placebo Comparator: Placebo
All participants will undergo three phases in random order:
The placebo phase will include overencapsulated placebo, matched to overencapsulated active agents, 2 tablets 3 times daily
25mg three times daily, overencapsulated tablet, increased after 1 week to 50mg three times daily
Active Comparator: Cilostazol
50mg bd, overencapsulated tablet (with midday placebo), increased after 1 week to 100mg bd (with midday placebo)
- Middle cerebral arterial pulsatility index [ Time Frame: 3 weeks ]Difference in Gosling's pulsatility index after three weeks treatment with sildenafil versus placebo, in 75 patients
- Percentage increase in MCA velocity on 6% CO2 vs medical air [ Time Frame: 3 weeks ]
- Difference in cerebrovascular reactivity after 3 weeks of treatment with sildenafil versus placebo in 75 patients: cereborovascular reactivity calculated by the percentage increase in mean MCA velocity whilst breathing 6% CO2 compared to breathing medical air.
- Non-inferiority of 3 weeks of treatment with cilostazol 100mg bd compared to sildenafil 50mg tds for difference in Gosling's pulsatility index and cerebrovascular reactivity to 6% CO2.
- Reactivity of BOLD signal on MRI to 6% CO2 challenge [ Time Frame: 3 weeks ]Difference in cerebrovascular reactivity after 3 weeks of treatment with sildenafil versus placebo in 30 patients: cerebrovascular reactivity calculated by the percentage increase in BOLD signal on MRI whilst breathing 6% CO2 compared to breathing medical air.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03855332
|Contact: Dr A Webb, DPhilfirstname.lastname@example.org|
|University of Oxford||Recruiting|
|Oxford, Oxon, United Kingdom, OX39DU|
|Contact: Alastair Webb, DPhil +441865231601 email@example.com|
|Principal Investigator:||Dr A Webb, DPhil||University of Oxford|