Ischemic StrokePhase 3EnhanceNCT00868010
Enhancing Rehabilitation After Stroke
A Phase 3 study testing donepezil in people with Ischemic Stroke, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 2 sites in United States.
Trial summary
This is a 12-week, randomized, placebo controlled study to determine if donepezil (Aricept) treatment during rehabilitation after stroke improves functional recovery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ischemic Stroke
- What is being tested?
- donepezil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 2 sitesUnited States
- Study dates
- Mar 2009to Nov 2013
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- male or female;
- aged 18 or older;
- new ischemic stroke within the preceding 30 days; and
- admitted to the an inpatient facility of the UPMC Institute for Rehabilitation and Research for post-stroke rehabilitation.
Who cannot join
- primary hemorrhagic stroke;
- current use of a cholinomimetic drug including tacrine, donepezil, galantamine, and rivastigmine;
- contraindication to AchEi therapy including bradycardia (< 50 bpm), severe asthma or COPD requiring nebulized medication, and active upper GI bleed or untreated gastric ulcer;
- myocardial infarction, poorly controlled congestive heart failure, or coronary bypass surgery within the last 3 months;
- current required use of an anticholinergic medication (e.g., for bladder spasm);
- current aphasia severe enough to prevent valid neuropsychiatric assessment (e.g., a score < 9 on the Token Test, part I and a score of < 14 (or <80% accuracy) on the repetition task of the Boston Diagnostic Aphasia Examination);
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- current Major Depressive Episode AND HRSD > 20;
- current active suicidal ideation, plan, or intent;
- current mania or hypomania;
- current psychosis;
- meeting DMS-IV TR alcohol or substance abuse or dependence criteria within the preceding 3 months;
- subject and/or family informant do not speak English;
- history of a progressive or unstable CNS disease (e.g., multiple sclerosis, Parkinson's disease, HIV with CNS involvement);
- medically unstable (determined by review of the subject's medical status with the treating (clinical) physician and by review of standard blood tests); and
- history of sensitivity to donepezil;
- for potential subjects without a pacemaker or implantable defibrillator, exclusion criteria will include (a) ECG evidence of second or third degree heart block ( b ) ECG evidence of a tri-fascicular block (LBBB and 1st degree AV Block; RBBB, left anterior or left posterior hemiblock, and 1st degree AV block) or ( c ) history of syncope within 1 year with a RBBB or a LBBB.
- For females of child-bearing age, current pregnancy, plan to become pregnant while on study drug, or refusal to avoid pregnancy while on study drug.
- For females of child-bearing age, current breast feeding.
- suicidal attempt in the past one year,
- an inpatient admission for depression in the past one year
Trial locations and contacts
2 sites in 1 country.
United States2 sites, 2 recruiting
- Recruiting
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
Kara Kenton, 412-246-5815, kentonkd@upmc.edu
Howard Aizenstein, MD, PhD
- Not yet recruiting
Hillside Rehabilitation Hospital
Warren, Ohio, 44484
Nancy Landgraff, PhD, 330-941-2703, nlandgra@cc.ysu.edu
Nancy Landgraff, PhD
About this study
Official title: Donepezil to Promote Functional Recovery Post-stroke
This is a 12-week, randomized, placebo controlled study to determine if donepezil (Aricept) treatment during rehabilitation after stroke improves functional recovery.
Read the detailed description
Stroke is a leading cause of disability in the US (Thom 2006). The total number of stroke survivors (currently estimated as 5.5 million Americans) will continue to increase as the population ages and as the medical management of acute stroke continues to improve. Given stroke's devastating impact on activities of daily living and the large numbers of Americans afflicted, improving acute medical rehabilitation outcomes after stroke is of great public health importance.
Predictors of poor functional recovery post-stroke include impairments in cognition and motivation. Recent evidence indicates that acetylcholinesterase inhibitors may improve cognition and motivation; hence, their use post-stroke may lead to improved rehabilitation outcomes. Our group has demonstrated that use of the acetylcholinesterase inhibitor donepezil is associated with improved functional recovery in a pilot sample (n = 40) of elderly, cognitively impaired stroke survivors undergoing inpatient rehabilitation. Specifically, in this 12 week open-label study, those subjects receiving donepezil experienced a clinically meaningful 14 point greater improvement on the Functional Independence Measure (FIM) than an archival comparator group.
Based on these promising pilot study results, we propose a 12-week randomized, double-blind, placebo-controlled trial (followed by a 12 week off-drug observation period) in order to test the efficacy of donepezil to promote post-stroke functional recovery in older, cognitively impaired stroke survivors undergoing inpatient rehabilitation. We will also use this randomized controlled trial to examine the drug's effect on cognition post-stroke; specifically, the drug's effect on those cognitive domains (attention/working memory, information psychomotor speed, and episodic memory) that are relevant to functional outcomes.
- Conditions
- Ischemic Stroke
- Being tested
- donepezil, placebo
- Keywords
- stroke, donepezil, recovery
- Medical subject headings
- Ischemic Stroke, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
donepezilDrug
Also called Aricept
5 mg or 10 mg, titrated per drug insert. Participants may remain in the study at 5 mg if unable to tolerate 10 mg.
placeboDrug
Participants will receive a placebo pill for 12 weeks if randomized to this treatment.
| Study group | Role | What they receive |
|---|---|---|
| 1: donepezil | Experimental | Participants will receive treatment for 12 weeks on donepezil 10 mg (or 5 mg if unable to tolerate 10 mg). Treatment will be then be terminated and participants followed for another 12 weeks naturalistically. Receives: Drug: donepezil |
| 2. placebo | Placebo comparator | Participants will receive treatment for 12 weeks with placebo pill. Treatment will be then be terminated and participants followed for another 12 weeks naturalistically. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Functional Independence Measure (FIM)
Measured: Weekly/12 weeks
Secondary outcomes (1)
Cognitive Function (ImPACT battery used to assess attention - working memory continuum, information processing speed, and verbal and visual episodic memory.)
Measured: Multiple time points over 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2009 (estimated)
- Study startMar 2009
- Primary completionAug 2013 (estimated)
- Study completionNov 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Ischemic StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Ellen Whyte, University of Pittsburgh
- Investigators
- Ellen M Whyte, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00868010
- Sponsor's protocol ID
- 1R01HD055525
- Other IDs
- NIH grant: 1 R01 HD055525-01A2
- Acronym
- Enhance
- Status last verified
- Mar 2013
- First submitted
- 22 Mar 2009
- Last updated
- 5 Mar 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Thom T, Haase N, Rosamond W, Howard VJ, Rumsfeld J, Manolio T, Zheng ZJ, Flegal K, O'Donnell C, Kittner S, Lloyd JD, Goff DC, Hong Y, (2006): Heart Disease and Stroke Statistics-2006 Update, American Heart Association: February 14, 2006. http://circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA.105.171600v1
Whyte EM, Lenze EJ, Butters M, Skidmore E, Koenig K, Dew MA, Penrod L, Mulsant BH, Pollock BG, Cabacungan L, Reynolds CF 3rd, Munin MC. An open-label pilot study of acetylcholinesterase inhibitors to promote functional recovery in elderly cognitively impaired stroke patients. Cerebrovasc Dis. 2008;26(3):317-21. doi: 10.1159/000149580. Epub 2008 Jul 31.
PubMed 18667813
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Donepezil to Promote Functional Recovery Post-stroke
- ClinicalTrials.gov ID
- NCT00868010
- Acronym / sponsor ID
- Enhance / 1R01HD055525
- Conditions
- Ischemic Stroke
- Keywords
- stroke, donepezil, recovery
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- Mar 2009
- Primary completion
- Aug 2013 (estimated)
- Study completion
- Nov 2013 (estimated)
- First posted
- 24 Mar 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a 12-week, randomized, placebo controlled study to determine if donepezil (Aricept) treatment during rehabilitation after stroke improves functional recovery.
Detailed description
Stroke is a leading cause of disability in the US (Thom 2006). The total number of stroke survivors (currently estimated as 5.5 million Americans) will continue to increase as the population ages and as the medical management of acute stroke continues to improve. Given stroke's devastating impact on activities of daily living and the large numbers of Americans afflicted, improving acute medical rehabilitation outcomes after stroke is of great public health importance.
Predictors of poor functional recovery post-stroke include impairments in cognition and motivation. Recent evidence indicates that acetylcholinesterase inhibitors may improve cognition and motivation; hence, their use post-stroke may lead to improved rehabilitation outcomes. Our group has demonstrated that use of the acetylcholinesterase inhibitor donepezil is associated with improved functional recovery in a pilot sample (n = 40) of elderly, cognitively impaired stroke survivors undergoing inpatient rehabilitation. Specifically, in this 12 week open-label study, those subjects receiving donepezil experienced a clinically meaningful 14 point greater improvement on the Functional Independence Measure (FIM) than an archival comparator group.
Based on these promising pilot study results, we propose a 12-week randomized, double-blind, placebo-controlled trial (followed by a 12 week off-drug observation period) in order to test the efficacy of donepezil to promote post-stroke functional recovery in older, cognitively impaired stroke survivors undergoing inpatient rehabilitation. We will also use this randomized controlled trial to examine the drug's effect on cognition post-stroke; specifically, the drug's effect on those cognitive domains (attention/working memory, information psychomotor speed, and episodic memory) that are relevant to functional outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1: donepezil | Experimental | Drug: donepezilParticipants will receive treatment for 12 weeks on donepezil 10 mg (or 5 mg if unable to tolerate 10 mg). Treatment will be then be terminated and participants followed for another 12 weeks naturalistically. |
| 2. placebo | Placebo comparator | Drug: placeboParticipants will receive treatment for 12 weeks with placebo pill. Treatment will be then be terminated and participants followed for another 12 weeks naturalistically. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- male or female;
- aged 18 or older;
- new ischemic stroke within the preceding 30 days; and
- admitted to the an inpatient facility of the UPMC Institute for Rehabilitation and Research for post-stroke rehabilitation.
Key exclusion criteria (20 listed)
- primary hemorrhagic stroke;
- current use of a cholinomimetic drug including tacrine, donepezil, galantamine, and rivastigmine;
- contraindication to AchEi therapy including bradycardia (< 50 bpm), severe asthma or COPD requiring nebulized medication, and active upper GI bleed or untreated gastric ulcer;
- myocardial infarction, poorly controlled congestive heart failure, or coronary bypass surgery within the last 3 months;
- current required use of an anticholinergic medication (e.g., for bladder spasm);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| donepezilAlso: Aricept5 mg or 10 mg, titrated per drug insert. Participants may remain in the study at 5 mg if unable to tolerate 10 mg. | Drug | 1: donepezil |
| placeboParticipants will receive a placebo pill for 12 weeks if randomized to this treatment. | Drug | 2. placebo |
Primary outcome
Functional Independence Measure (FIM)
Time frame: Weekly/12 weeks
1 secondary outcome
Cognitive Function (ImPACT battery used to assess attention - working memory continuum, information processing speed, and verbal and visual episodic memory.)
Time frame: Multiple time points over 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2013.
- BackgroundThom T, Haase N, Rosamond W, Howard VJ, Rumsfeld J, Manolio T, Zheng ZJ, Flegal K, O'Donnell C, Kittner S, Lloyd JD, Goff DC, Hong Y, (2006): Heart Disease and Stroke Statistics-2006 Update, American Heart Association: February 14, 2006. http://circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA.105.171600v1
- Background: PubMed 18667813Whyte EM, Lenze EJ, Butters M, Skidmore E, Koenig K, Dew MA, Penrod L, Mulsant BH, Pollock BG, Cabacungan L, Reynolds CF 3rd, Munin MC. An open-label pilot study of acetylcholinesterase inhibitors to promote functional recovery in elderly cognitively impaired stroke patients. Cerebrovasc Dis. 2008;26(3):317-21. doi: 10.1159/000149580. Epub 2008 Jul 31.
- American Stroke Association website provides general information regarding stroke and stroke prevention.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ellen M Whyte, MD principal investigator
University of Pittsburgh
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing donepezil in people with Ischemic Stroke, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Mar 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kara Kenton (412-246-5815, kentonkd@upmc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Functional Independence Measure (FIM) (time frame: Weekly/12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00868010, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2013; AzTrials last refreshed its copy on 29 Oct 2026.