Effects of Donepezil on Regional Cerebral Blood Flow Following Aneurysmal Subarachnoid Haemorrhage
Status:
Terminated
Trial end date:
2016-11-01
Target enrollment:
Participant gender:
Summary
Introduction
Aneurysmal subarachnoid hemorrhage (aSAH) is bleeding around the under surface of the brain
caused by rupture of an aneurysm arising from a blood vessel. Stroke may occur in
approximately one third of patients as a result of narrowing of the blood vessels around the
brain, following aSAH.
One theory as to why this may happen is because bleeding around the base of the brain damages
particular cells (neurons) that control blood flow around the rest of the brain. These
neurons may control blood flow by releasing a neurotransmitter called Acetyl Choline (ACh).
Our hypothesis is that damage to these neurons may prevent the production of ACh, which then
causes reduced blood flow and stroke if left untreated.
By stimulating these neurons, we aim to investigate whether it is possible to improve the
blood flow around brain and ultimately prevent strokes in patients following subarachnoid
haemorrhage. Donepezil, a drug widely used in dementia, inhibits the brain's natural break
down of ACh. We predict that by increasing the amount of Ach in these neurons, donepezil may
improve blood flow to the brain, reducing the chance of developing stroke.
Trial Protocol
All patients admitted to St George's hospital with a confirmed aneurysmal subarachnoid
haemorrhage between the ages of 18 and 85 years old will be invited to participate in the
trial. The protocol has been designed to take place around the patients' aneurysm treatment,
which is performed under general anesthesia (GA). Recruited participants will be anesthetized
for their aneurysm treatment and then enter the study.
All trial participants will have a Xenon CT scan under GA to assess brain blood flow prior to
having treatment of their aneurysm. Patients randomized to donepezil treatment will receive a
loading dose of 20mg via a feeding tube immediately after their Xenon scan. Patients in the
control group will not receive the drug.
All patients in the trial will undergo repeat Xenon perfusion scanning under GA between 3 and
4 hours after their first scan, which coincides with the completion of their aneurysm
treatment. Those in the donepezil group will then receive a daily dose of 5 mg for a period
of 21 days.
All aspects of care other than those related to the trial will be the same as for any other
subarachnoid haemorrhage patients. Patients (or their legal representative for those unable
to consent) will be able to decline participation in the trial or withdraw at any point.