MASTER: Mayo Acute Stroke Trial for Enhancing Recovery

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT00805792
• Collaborator: (none)
• Enrollment: 33
• Location: 1
• Arm: 1
• Duration (Months): 22
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

This study involves treating patients that have suffered an acute ischemic stroke with the medication donepezil (Aricept ®). The hypothesis is that taking donepezil (FDA-approved for the treatment of Alzheimer's Disease) for the first 90 days following a stroke enhances recovery.

Condition or Disease	Intervention/Treatment	Phase
Ischemic Stroke	Drug: Donepezil	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Mayo Acute Stroke Trial for Enhancing Recovery
• Study Start Date: Nov 1, 2008
• Actual Primary Completion Date: Sep 1, 2010
• Actual Study Completion Date: Sep 1, 2010

Arms and Interventions

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.	Drug: Donepezil; 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: Aricept

Outcome Measures

Primary Outcome Measures

1. Percent of Participants With National Institutes of Health Stroke Scale (NIHSS) Score = 0 or 1 at Day 90 [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).

Secondary Outcome Measures

1. Change in Mean National Institutes of Health Stroke Scale (NIHSS) Score at 90 Days Post-stroke [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).

2. Change in Mean Barthel Index of Activities of Daily Living Score at 90 Days Post-stroke [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.

3. Change in Mean Score on Mini Mental State Exam at 90 Days Post-stroke [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.

4. Change in Time to Complete Neuropsychological Trail Making Tests A and B at 90 Days Post-stroke [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.).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Jacksonville	Florida	United States	32224

Sponsors and Collaborators

• Mayo Clinic

Investigators

• Principal Investigator: James F. Meschia, M.D., Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Mayo Clinic Clinical Trials

Publications

• 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.
• 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.

• Responsible Party: James F. Meschia, Principal Investigator, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT00805792
• Other Study ID Numbers: 08-005098
• First Posted: Dec 10, 2008
• Last Update Posted: Jul 30, 2021
• Last Verified: Jul 1, 2021

• Keywords provided by James F. Meschia, Principal Investigator, Mayo Clinic: Ischemic stroke; treatment; recovery; donepezil; Aricept
• Additional relevant MeSH terms: Stroke; Ischemic Stroke; Donepezil

Study Results

Participant Flow

Recruitment Details	Enrollment extended from November 2008 through April 2010. The study was conducted at the Mayo Clinic sites in Jacksonville, FL and Rochester, MN.

Arm/Group Title	Donepezil
Arm/Group Description	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.
Period Title: Overall Study
STARTED	33
COMPLETED	28
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Donepezil
Arm/Group Description	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.
Overall Participants	33
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	66
Sex: Female, Male (Count of Participants)
Female	16 48.5%
Male	17 51.5%
Region of Enrollment (participants) [Number]
United States	33 100%
Number of Participants with Previous Ischemic Stroke (participants) [Number]
Previous ischemic stroke	5 15.2%
No previous ischemic stroke	28 84.8%
Body Mass Index (kg/m^2) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kg/m^2]	27.1
Participant Scores on National Institutes of Health Stroke Scale (participants) [Number]
Mild (<6)	16 48.5%
Moderate (6-13)	12 36.4%
Severe (>13)	5 15.2%

Outcome Measures

1. Primary Outcome

Title	Percent of Participants With National Institutes of Health Stroke Scale (NIHSS) Score = 0 or 1 at Day 90
Description	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).
Time Frame	90 days post-stroke

Outcome Measure Data

Analysis Population Description

Intention-to-treat analysis, all treated participants (n=33). Unobserved because of death (n=3) or loss to follow up (N=2) treated as nonresponse.

Arm/Group Title	Donepezil
Arm/Group Description	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.
Measure Participants	33
Stroke severity (NIHSS) mild (<6) (n=11/16)	69 209.1%
Stroke severity (NIHSS) moderate (6-13) (n=4/12)	33 100%
Stroke severity (NIHSS) severe (>13) (n=0/5)	0 0%
Overall (n=15/33)	45 136.4%

2. Secondary Outcome

Title	Change in Mean National Institutes of Health Stroke Scale (NIHSS) Score at 90 Days Post-stroke
Description	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).
Time Frame	baseline, 90 days post-stroke

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Donepezil
Arm/Group Description	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.
Measure Participants	33
Mean (Standard Error) [units on a scale]	-2.8 (0.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Donepezil
	Comments	The statistical significance of the change was assessed by the P value associated with estimated regression coefficient (beta coefficient or slope).
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	Regression, Linear
	Comments

3. Secondary Outcome

Title	Change in Mean Barthel Index of Activities of Daily Living Score at 90 Days Post-stroke
Description	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.
Time Frame	baseline, 90 days post-stroke

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Donepezil
Arm/Group Description	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.
Measure Participants	33
Mean (Standard Error) [units on a scale]	21.4 (5.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Donepezil
	Comments	The statistical significance of the change was assessed by the P value associated with estimated regression coefficient (beta coefficient or slope).
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	Regression, Linear
	Comments

4. Secondary Outcome

Title	Change in Mean Score on Mini Mental State Exam at 90 Days Post-stroke
Description	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.
Time Frame	baseline, 90 days post-stroke

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Donepezil
Arm/Group Description	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.
Measure Participants	33
Mean (Standard Error) [units on a scale]	4.4 (1.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Donepezil
	Comments	The statistical significance of the change was assessed by the P value associated with estimated regression coefficient (beta coefficient or slope).
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	Regression, Linear
	Comments

5. Secondary Outcome

Title	Change in Time to Complete Neuropsychological Trail Making Tests A and B at 90 Days Post-stroke
Description	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.).
Time Frame	baseline, 90 days post-stroke

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Donepezil
Arm/Group Description	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.
Measure Participants	33
Trail Making Test A	-43.4 (9.2)
Trail Making Test B	-67.3 (13.3)

Adverse Events

Time Frame	Adverse events were collected during the 90-day course of therapy.
Arm/Group Title	Donepezil
Arm/Group Description	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.
All Cause Mortality
	Donepezil
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Donepezil
	Affected / at Risk (%)	# Events
Total	10/33 (30.3%)
Cardiac disorders
Myocardial infarction	1/33 (3%)	1
Hypertension	1/33 (3%)	1
General disorders
Death	3/33 (9.1%)	3
Musculoskeletal and connective tissue disorders
Chest pain/leg cramps	1/33 (3%)	1
Vascular disorders
Recurrent stroke	2/33 (6.1%)	2
Transient ischemic attack	1/33 (3%)	1
Carotid angioplasty and stent placement	1/33 (3%)	1
Other (Not Including Serious) Adverse Events
	Donepezil
	Affected / at Risk (%)	# Events
Total	33/33 (100%)
Gastrointestinal disorders
Nausea	11/33 (33.3%)	11
Loss of appetite	10/33 (30.3%)	10
General disorders
Fatigue	17/33 (51.5%)	17
Insomnia	16/33 (48.5%)	16
Musculoskeletal and connective tissue disorders
Muscle cramps	10/33 (30.3%)	10
Psychiatric disorders
Depression	13/33 (39.4%)	13

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.