A Phase 2 interventional study of Donepezil in Ischemic Stroke, sponsored by Mayo Clinic. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-07-30.
Sponsored by Mayo Clinic · Phase 2, Interventional, and Treatment
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.
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.
7,286 studies on the registry are indexed under Stroke; 2,007 are open to participants now.
This study's enrollment of 33 is below the median of 50 across 5,369 interventional studies indexed under Stroke.
Browse Stroke studies →Mayo Clinic is the lead sponsor of 3,218 studies on the registry; 670 are open to participants now.
Of its 445 completed or terminated interventional studies of FDA-regulated products, 313 (70%) have results posted.
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Exclusion Criteria:
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.
Also known as: Aricept
Percent of Participants With National Institutes of Health Stroke Scale (NIHSS) Score = 0 or 1 at Day 90
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
Change in Mean National Institutes of Health Stroke Scale (NIHSS) Score at 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).
Time frame: baseline, 90 days post-stroke
Change in Mean Barthel Index of Activities of Daily Living Score at 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.
Time frame: baseline, 90 days post-stroke
Change in Mean Score on Mini Mental State Exam at 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.
Time frame: baseline, 90 days post-stroke
Change in Time to Complete Neuropsychological Trail Making Tests A and B at 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.).
Time frame: baseline, 90 days post-stroke
Enrollment extended from November 2008 through April 2010. The study was conducted at the Mayo Clinic sites in Jacksonville, FL and Rochester, MN.
| Milestone | Donepezil |
|---|---|
| Started | 33 |
| Completed | 28 |
| Not completed | 5 |
| Withdrew: Death | 3 |
| Withdrew: Lost to follow-up | 2 |
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).
| percentage of participants | Donepezil |
|---|---|
| Stroke severity (NIHSS) mild (<6) (n=11/16) | 69 |
| Stroke severity (NIHSS) moderate (6-13) (n=4/12) | 33 |
| Stroke severity (NIHSS) severe (>13) (n=0/5) | 0 |
| Overall (n=15/33) | 45 |
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).
| units on a scale | Donepezil |
|---|---|
| Change in Mean National Institutes of Health Stroke Scale (NIHSS) Score at 90 Days Post-stroke | -2.8 ± 0.8 |
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.
| units on a scale | Donepezil |
|---|---|
| Change in Mean Barthel Index of Activities of Daily Living Score at 90 Days Post-stroke | 21.4 ± 5.2 |
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.
| units on a scale | Donepezil |
|---|---|
| Change in Mean Score on Mini Mental State Exam at 90 Days Post-stroke | 4.4 ± 1.2 |
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.).
| seconds | Donepezil |
|---|---|
| Trail Making Test A | -43.4 ± 9.2 |
| Trail Making Test B | -67.3 ± 13.3 |
Collected over Adverse events were collected during the 90-day course of therapy.. Non-serious events are listed at a 3% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Donepezil | — | 10/33 (30.3%) | 33/33 (100%) |
| Event | Donepezil |
|---|---|
| DeathGeneral disorders | 3/33 |
| Recurrent strokeVascular disorders | 2/33 |
| Transient ischemic attackVascular disorders | 1/33 |
| Myocardial infarctionCardiac disorders | 1/33 |
| Carotid angioplasty and stent placementVascular disorders | 1/33 |
| HypertensionCardiac disorders | 1/33 |
| Chest pain/leg crampsMusculoskeletal and connective tissue disorders | 1/33 |
| Event | Donepezil |
|---|---|
| FatigueGeneral disorders | 17/33 |
| InsomniaGeneral disorders | 16/33 |
| DepressionPsychiatric disorders | 13/33 |
| NauseaGastrointestinal disorders | 11/33 |
| Loss of appetiteGastrointestinal disorders | 10/33 |
| Muscle crampsMusculoskeletal and connective tissue disorders | 10/33 |
| Age, Continuous(years) | Donepezil |
|---|---|
| Median | 66 (54 to 84) |
| Sex: Female, Male(Participants) | Donepezil |
|---|---|
| Female | 16 |
| Male | 17 |
| Region of Enrollment(participants) | Donepezil |
|---|---|
| United States | 33 |
| Number of Participants with Previous Ischemic Stroke(participants) | Donepezil |
|---|---|
| Previous ischemic stroke | 5 |
| No previous ischemic stroke | 28 |
| Body Mass Index(kg/m^2) | Donepezil |
|---|---|
| Median | 27.1 (24.7 to 30.6) |
| Participant Scores on National Institutes of Health Stroke Scale(participants) | Donepezil |
|---|---|
| Mild (<6) | 16 |
| Moderate (6-13) | 12 |
| Severe (>13) | 5 |
This study is completed, as verified in Jul 2021. You cannot join it, but the record below documents what was studied.
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