Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 3 of 331 for:    DONEPEZIL

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02222727
Recruitment Status : Terminated (CT scanner software incompatible)
First Posted : August 21, 2014
Last Update Posted : September 11, 2017
Sponsor:
Information provided by (Responsible Party):
St George's, University of London

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.


Condition or disease Intervention/treatment Phase
Aneurysmal Subarachnoid Hemorrhage Delayed Neurological Deficit Delayed Cerebral Ischemia Vasospasm Drug: Donepezil Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effects of Donepezil on Regional Cerebral Blood Flow Following Aneurysmal Subarachnoid Haemorrhage
Study Start Date : January 2014
Actual Primary Completion Date : November 2016
Actual Study Completion Date : November 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding

Arm Intervention/treatment
Active Comparator: 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.
Drug: Donepezil
Loading 20 mg dose of donepezil on first day of recruitment followed by once daily 5 mg dose for subsequent twenty days
Other Name: Aricept

No Intervention: 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.



Primary Outcome Measures :
  1. Cerebral blood flow [ Time Frame: Within 3-4 hours of receiving drug ]

    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 :
  1. Number of participants with adverse events. [ Time Frame: 6 weeks from enrolment ]

    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.


  2. Disability assessment [ Time Frame: 6 months from enrolment ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

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): NCT02222727


Locations
Layout table for location information
United Kingdom
St George's University of London
London, United Kingdom, SW17 0RE
Sponsors and Collaborators
St George's, University of London
Investigators
Layout table for investigator information
Study Director: Jeremy Madigan, FRCR St George's Hospital NHS Trust
Principal Investigator: Ramanan Sivakumaran, MRCS St George's, University of London
Principal Investigator: Marios Papadopouos, MD FRCS(SN) St George's, University of London
Principal Investigator: Kunle Mduaoi St George's, University of London

Layout table for additonal information
Responsible Party: St George's, University of London
ClinicalTrials.gov Identifier: NCT02222727     History of Changes
Other Study ID Numbers: 13.0099
2013-002457-30 ( EudraCT Number )
First Posted: August 21, 2014    Key Record Dates
Last Update Posted: September 11, 2017
Last Verified: September 2017
Additional relevant MeSH terms:
Layout table for MeSH terms
Donepezil
Subarachnoid Hemorrhage
Brain Ischemia
Cerebral Infarction
Hemorrhage
Ischemia
Pathologic Processes
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Stroke
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Nootropic Agents