- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00805792
Mayo Acute Stroke Trial for Enhancing Recovery (MASTER)
Study Overview
Detailed Description
We hypothesize that donepezil (5 mg per day, titrated up to 10 mg per day as tolerated) will enhance recovery following stroke by improving attention, learning and memory thereby enhancing rehabilitation. The null hypothesis is that the probability of a favorable outcome among post-stroke donepezil users is equal to that observed among similar participants in an existing National Institutes of Neurological Disorders and Stroke (NINDS) resource, the Phase III clinical trial of Tissue Plasminogen Activator (tPA) for acute ischemic stroke. The NINDS tPA stroke trial has been used as historical control data in pilot trials of reperfusion and neuroprotection.
The MASTER trial will be a multicenter, single-arm NINDS Recominant tPA trial-controlled, modified 2-stage adaptive clinical trial set in 2 tertiary care hospitals in the United States. Participants will be men and women with acute (< 24 hours of onset of symptoms) ischemic stroke. A favorable outcome will be defined as National Institutes of Health Stroke Scale (NIHSS) values of 0 or 1 at 90 days post-stroke.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Florida
-
Jacksonville, Florida, United States, 32224
- Mayo Clinic
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Definite or probable acute ischemic cerebrovascular syndrome (AICS), as defined by Kidwell et al (Stroke. 2003;34:2995-8).
- Experimental treatment started within 24 hours of onset of symptoms.
- Age ≥ 18 years.
- Ability and willingness to return for follow-up visits.
- Willingness of an available informant who knows the patient well to participate in informant-based questionnaires for the duration of the follow-up period.
- Living in independent or semi-independent living situation before the stroke.
- Fluent in English before the stroke.
- Provides written informed consent.
- Near visual acuity of at least 20/200 in at least one eye.
- Auditory acuity of at least having the ability to detect finger rubbing in at least one ear.
Exclusion Criteria:
- Parkinson's disease or restless leg syndrome.
- Partial or generalized seizures.
- No acute decompensated heart failure
- Routinely requiring daytime supplemental oxygen before the stroke; study participants on continuous positive air pressure (CPAP) for obstructive sleep apnea remain eligible.
- Gastrointestinal or genitourinary surgery within 1 month of screening.
- Gastrointestinal bleeding.
- Syncope or symptomatic bradycardia.
- Creatinine ≥ 3.5 mg/dL or requiring dialysis.
- Peptic ulcer disease.
- Asthma.
- Tracheostomy or endotracheal intubation.
- Taking donepezil or other acetylcholinesterase inhibitor at screening.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Donepezil
Participants received treatment with donepezil within 24 hours after the onset of ischemic stroke symptoms.
Participants received donepezil 5 mg/day for 30 days, followed by an increase to 10 mg/day for 60 days.
|
Study participants will be treated with donepezil orally at an initial dose of 5 mg daily for the first 4 weeks, then increased at their 30-day visit by 5 mg to a maximum dose of 10 mg daily, if tolerated.
If the participant does not tolerate the 10 mg dose, they will remain on 5 mg through the course of the study.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent of Participants With National Institutes of Health Stroke Scale (NIHSS) Score = 0 or 1 at Day 90
Time Frame: 90 days post-stroke
|
The National Institutes of Health Stroke Scale (NIHSS) is a 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss.
A trained observer rates the patent's ability to answer questions and perform activities.
Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items.
The range of scores is from 0 (normal) to 42 (profound effect of stroke on patient).
|
90 days post-stroke
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Mean National Institutes of Health Stroke Scale (NIHSS) Score at 90 Days Post-stroke
Time Frame: baseline, 90 days post-stroke
|
The National Institutes of Health Stroke Scale (NIHSS) is a 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss.
A trained observer rates the patent's ability to answer questions and perform activities.
Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items.
The range of scores is from 0 (normal) to 42 (profound effect of stroke on patient).
|
baseline, 90 days post-stroke
|
Change in Mean Barthel Index of Activities of Daily Living Score at 90 Days Post-stroke
Time Frame: baseline, 90 days post-stroke
|
The Barthel Index of Activities of Daily Living (ADLs) measures functional disability by quantifying patient performance in 10 activities of daily life.
These activities can be grouped according to self-care (feeding, grooming, bathing, dressing, bowel and bladder care, and toilet use) and mobility (ambulation, transfers, and stair climbing).
5-point increments are used in scoring, with a maximal score of 100 indicating that a patient is fully independent in physical functioning, and a lowest score of 0 representing a totally dependent bed-ridden state.
|
baseline, 90 days post-stroke
|
Change in Mean Score on Mini Mental State Exam at 90 Days Post-stroke
Time Frame: baseline, 90 days post-stroke
|
The mini-mental state examination (MMSE) is a 30-point questionnaire test that is used to screen for cognitive impairment.
The questionnaire samples functions including arithmetic, memory and orientation to time and place.
Scores range from 0 to 30.
Any score greater than or equal to 25 points is effectively normal (intact).
Below this, scores can indicate severe (≤9 points), moderate (10-20 points) or mild (21-24 points) cognitive impairment.
|
baseline, 90 days post-stroke
|
Change in Time to Complete Neuropsychological Trail Making Tests A and B at 90 Days Post-stroke
Time Frame: baseline, 90 days post-stroke
|
The Trail-making test consists of two parts in which the subject is instructed to connect a set of 25 dots as fast as possible while still maintaining accuracy.
It can provide information about visual search speed, scanning, speed of processing, mental flexibility, as well as executive functioning.
There are two parts to the test: A, in which the targets are all numbers (1,2,3, etc.)and the test taker needs to connect them in sequential order, and B, in which the subject alternates between numbers and letters (1, A, 2, B, etc.).
|
baseline, 90 days post-stroke
|
Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995 Dec 14;333(24):1581-7. doi: 10.1056/NEJM199512143332401.
- Meschia JF, McNeil RB, Barrett KM, Brott TG, Graff-Radford NR, Brown RD Jr. Mayo Acute Stroke Trial for Enhancing Recovery (MASTER) protocol. J Stroke Cerebrovasc Dis. 2010 Jul-Aug;19(4):299-310. doi: 10.1016/j.jstrokecerebrovasdis.2009.05.005.
- Barrett KM, Brott TG, Brown RD Jr, Carter RE, Geske JR, Graff-Radford NR, McNeil RB, Meschia JF; Mayo Acute Stroke Trial for Enhancing Recovery (MASTER) Study Group. Enhancing recovery after acute ischemic stroke with donepezil as an adjuvant therapy to standard medical care: results of a phase IIA clinical trial. J Stroke Cerebrovasc Dis. 2011 May-Jun;20(3):177-82. doi: 10.1016/j.jstrokecerebrovasdis.2010.12.009. Epub 2011 Feb 3.
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Cerebrovascular Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Stroke
- Ischemic Stroke
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Cholinergic Agents
- Enzyme Inhibitors
- Nootropic Agents
- Cholinesterase Inhibitors
- Donepezil
Other Study ID Numbers
- 08-005098
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Ischemic Stroke
-
Nordsjaellands HospitalRigshospitalet, Denmark; Metropolitan University CollegeCompletedTransient Ischemic Attack | Stroke, Ischemic | Stroke HemorrhagicDenmark
-
University of CalgaryThe George Institute for Global Health, AustraliaNot yet recruitingAcute Ischemic Stroke AIS | Stroke, Acute, Stroke Ischemic | Stroke AcuteCanada, Australia
-
Second Affiliated Hospital, School of Medicine,...Shanghai Zhongshan Hospital; First Affiliated Hospital of Wenzhou Medical University and other collaboratorsRecruitingAcute Ischemic Stroke and Transient Ischemic AttacksChina
-
Medtronic Cardiac Rhythm and Heart FailureMedtronic Bakken Research CenterCompletedCryptogenic Symptomatic Transient Ischemic Attack | Cryptogenic Ischemic StrokeNetherlands, United States, France, Belgium, Germany, Sweden, Italy, Austria, Canada, Denmark, Finland, Greece, Slovakia, Spain
-
University Hospital, BrestCompletedStroke, Ischemic | Stroke HemorrhagicFrance
-
Umbria Bioengineering TechnologiesRecruitingStroke, Ischemic | Stroke HemorrhagicItaly
-
Sheffield Teaching Hospitals NHS Foundation TrustUnknownFatigue | Stroke, Ischemic | Stroke HemorrhagicUnited Kingdom
-
BayerRecruitingAcute Non-cardioembolic Ischemic Stroke | Prevention of Ischemic Stroke | High-risk Transient Ischemic AttackUnited States, Switzerland, Belgium, Australia, Sweden, Canada, Taiwan, Spain, Korea, Republic of, Latvia, Israel, Malaysia, China, Greece, Japan, Turkey, Netherlands, Romania, United Kingdom, Portugal, Hungary, Italy, Brazil, France, S... and more
-
University of AlbertaCompletedTransient Ischemic Attack | Minor Ischemic StrokeCanada
-
Ischemia Care LLCCompletedIschemic Stroke | Atrial Fibrillation | Thrombotic Stroke | Transient Ischemic Attacks | Cardioembolic Stroke | Stroke of Basilar Artery | Transient Cerebrovascular EventsUnited States
Clinical Trials on Donepezil
-
Eisai Co., Ltd.CompletedDementia With Lewy Bodies (DLB)Japan
-
Eisai Inc.Eisai LimitedCompleted
-
Corium, Inc.CompletedAlzheimer DiseaseUnited States
-
Samsung Medical CenterEisai Korea Inc.CompletedDementia | Alzheimer's DiseaseKorea, Republic of
-
Eisai Co., Ltd.CompletedDementia With Lewy Bodies (DLB)Japan
-
Eisai Inc.PfizerTerminatedCognitive Dysfunction | Down SyndromeUnited States
-
Eisai Inc.PfizerTerminatedCognitive Dysfunction | Down SyndromeUnited States
-
Eisai Inc.CompletedMigraine HeadacheUnited States
-
The First Affiliated Hospital with Nanjing Medical...Unknown
-
Shanghai Synergy Pharmaceutical Sciences Co., Ltd.Completed