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

Primary Purpose

Aneurysmal Subarachnoid Hemorrhage, Delayed Neurological Deficit, Delayed Cerebral Ischemia

Status
Terminated
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Donepezil
Sponsored by
St George's, University of London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Aneurysmal Subarachnoid Hemorrhage

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • St George's University of London

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

Donepezil

Control

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Cerebral blood flow
Baseline xenon perfusion CT (XeCTP) scan performed immediately before donepezil loading dose administered. Follow-up XeCTP scan minimum of 3 hours after loading dose. For control group patients, baseline XeCTP scan performed before aneurysm treatment and follow-up scan 3-4 hours after first scan.

Secondary Outcome Measures

Number of participants with adverse events.
Participants receiving donepezil will continue to take for 21 days in total and the washout period for the drug is approximately 2 weeks accounting for a total evaluation period of 5-6 weeks. All participants will be regularly evaluated by clinical staff while inpatients under care of the neurosurgical service. Those discharged prior to the 6 week period will be followed up regularly by telephone and provided with a diary to record potential adverse events.
Disability assessment
All participants will have a modified Rankin Score (mRS) at 6 months to assess their level of disability in comparison with their status on enrolment.

Full Information

First Posted
August 20, 2014
Last Updated
September 8, 2017
Sponsor
St George's, University of London
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1. Study Identification

Unique Protocol Identification Number
NCT02222727
Brief Title
Effects of Donepezil on Regional Cerebral Blood Flow Following Aneurysmal Subarachnoid Haemorrhage
Acronym
DASH
Official Title
Effects of Donepezil on Regional Cerebral Blood Flow Following Aneurysmal Subarachnoid Haemorrhage
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Terminated
Why Stopped
CT scanner software incompatible
Study Start Date
January 2014 (undefined)
Primary Completion Date
November 2016 (Actual)
Study Completion Date
November 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
St George's, University of London

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aneurysmal Subarachnoid Hemorrhage, Delayed Neurological Deficit, Delayed Cerebral Ischemia, Vasospasm

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Donepezil
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Control
Arm Type
No Intervention
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Donepezil
Other Intervention Name(s)
Aricept
Intervention Description
Loading 20 mg dose of donepezil on first day of recruitment followed by once daily 5 mg dose for subsequent twenty days
Primary Outcome Measure Information:
Title
Cerebral blood flow
Description
Baseline xenon perfusion CT (XeCTP) scan performed immediately before donepezil loading dose administered. Follow-up XeCTP scan minimum of 3 hours after loading dose. For control group patients, baseline XeCTP scan performed before aneurysm treatment and follow-up scan 3-4 hours after first scan.
Time Frame
Within 3-4 hours of receiving drug
Secondary Outcome Measure Information:
Title
Number of participants with adverse events.
Description
Participants receiving donepezil will continue to take for 21 days in total and the washout period for the drug is approximately 2 weeks accounting for a total evaluation period of 5-6 weeks. All participants will be regularly evaluated by clinical staff while inpatients under care of the neurosurgical service. Those discharged prior to the 6 week period will be followed up regularly by telephone and provided with a diary to record potential adverse events.
Time Frame
6 weeks from enrolment
Title
Disability assessment
Description
All participants will have a modified Rankin Score (mRS) at 6 months to assess their level of disability in comparison with their status on enrolment.
Time Frame
6 months from enrolment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeremy Madigan, FRCR
Organizational Affiliation
St George's Hospital NHS Trust
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Ramanan Sivakumaran, MRCS
Organizational Affiliation
St George's, University of London
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Marios Papadopouos, MD FRCS(SN)
Organizational Affiliation
St George's, University of London
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kunle Mduaoi
Organizational Affiliation
St George's, University of London
Official's Role
Principal Investigator
Facility Information:
Facility Name
St George's University of London
City
London
ZIP/Postal Code
SW17 0RE
Country
United Kingdom

12. IPD Sharing Statement

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

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