Effects of Donepezil on Regional Cerebral Blood Flow Following Aneurysmal Subarachnoid Haemorrhage

NCT ID: NCT02222727

Last Updated: 2017-09-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2016-11-30

Brief 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.

Conditions

Aneurysmal Subarachnoid Hemorrhage; Delayed Neurological Deficit; Delayed Cerebral Ischemia; Vasospasm

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Donepezil

Participants in the donepezil arm will receive the drug for 21 days as specified in the protocol in addition to current best medical treatment for aSAH patients.

Group Type: ACTIVE_COMPARATOR

Donepezil

Intervention Type: DRUG

Loading 20 mg dose of donepezil on first day of recruitment followed by once daily 5 mg dose for subsequent twenty days

Control

Control group participants will not receive a placebo drug but will undergo cerebral blood flow imaging in the same manner as the donepezil patients. All other aspects of treatment will be identical to that of aSAH patients not involved in the study.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Donepezil

Loading 20 mg dose of donepezil on first day of recruitment followed by once daily 5 mg dose for subsequent twenty days

Intervention Type: DRUG

Other Intervention Names

Aricept

Eligibility Criteria

Inclusion Criteria

• age 18 - 85 years
• Fisher score 2-4
• recruitment within 12 - 72 hours of hemorrhage

Exclusion Criteria

• pregnancy
• breast feeding
• allergy to donepezil or other piperidine derivatives
• participants unwilling to use appropriate birth control up to 6 weeks after enrolment
• known dementia
• severe liver failure (Child-Pugh C)
• sick sinus syndrome or other supraventricular cardiac conduction abnormalities
• inspired oxygen requirement greater than 60%
• history of brittle asthma or obstructive airway disease
• aneurysm unsuitable for endovascular coiling
• concomitant use of cholinesterase inhibitor (e.g. rivastigmine, galantamine, etc)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St George's, University of London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeremy Madigan, FRCR

Role: STUDY_DIRECTOR

St George's Hospital NHS Trust

Ramanan Sivakumaran, MRCS

Role: PRINCIPAL_INVESTIGATOR

St George's, University of London

Marios Papadopouos, MD FRCS(SN)

Role: PRINCIPAL_INVESTIGATOR

St George's, University of London

Kunle Mduaoi

Role: PRINCIPAL_INVESTIGATOR

St George's, University of London

Locations

St George's University of London

London, , United Kingdom

Countries

United Kingdom

Other Identifiers

2013-002457-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

13.0099

Identifier Type: -

Identifier Source: org_study_id