Cerebrovascular Accident
Conditions
Keywords
Cholinesterase Inhibitors, Elderly, Stroke, Cognition
Brief summary
This study will evaluate the effectiveness of treatment with acetylcholinesterase inhibitors in improving cognitive function and overall rehabilitation in elderly stroke survivors.
Detailed description
Cognitive impairment is a common result of a stroke and can be detrimental to recovery. It can negatively affect both mental and physical functioning, thereby complicating the rehabilitation process. Although much research has targeted the effects of long-term cognitive impairment after a stroke, very little research has been done to examine the incidence and course of cognitive impairment during the first three months following a stroke. These first three months are the most important in terms of regaining function. Acetylcholinesterase inhibitors have been beneficial to both sufferers of vascular dementia and Alzheimer's disease. They may also be a useful pharmacologic intervention to enhance post-stroke rehabilitation. This study will compare the effectiveness of two acetylcholinesterase inhibitors, galantamine and donepezil, in improving cognitive function and overall rehabilitation in elderly stroke survivors. Participants in this open label study will be randomly assigned to receive either galantamine or donepezil for 12 weeks. Participants assigned to receive galantamine will receive 4 mg twice a day for 4 weeks, 8 mg twice a day for the next 4 weeks, and 12 mg twice a day for the remainder of the study. Participants assigned to receive donepezil will receive 5 mg twice a day for 6 weeks, and then 10 mg twice a day for the next 6 weeks. Functional independence will be measured at baseline and Weeks 2 and 12. In addition, a pre-stroke level of functional independence will be obtained through a structured interview with participants and their families. Participants will also be monitored for signs of depression and medication side effects throughout the study.
Interventions
DRUGGalantamine
Participants assigned to receive galantamine will receive 4 mg twice a day for 4 weeks, 8 mg twice a day for the next 4 weeks, and 12 mg twice a day for the remainder of the study.
DRUGDonepezil
Participants assigned to receive donepezil will receive 5 mg twice a day for 6 weeks, and then 10 mg twice a day for the next 6 weeks.
Sponsors
National Institute of Mental Health (NIMH)
University of Pittsburgh
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Admitted to a rehabilitation hospital with primary diagnosis of ischemic stroke (cardiovascular accident) * Stroke was within 30 days of being admitted * Medically stable * Presence of memory and/or attentional impairments and evidence that these impairments were not present or were less severe prior to the stroke (assessed via interview with family) * Approval by individual's attending physician at the rehabilitation hospital
Exclusion criteria
* Aphasia or cognitive (or behavioral) impairments severe enough to prevent valid neuropsychiatric assessment * Currently experiencing a major depressive episode (unless treated and in partial remission, assessed using the Primary Care Evaluation of Mental Disorders) * Current psychosis or mania * History of substance or alcohol abuse or dependence within three months of study entry * Currently taking a cholinomimetic drug * Medical condition with known sensitivity to donepezil (e.g., slower than normal heart rate, supraventricular cardiac conduction defects, severe asthma or obstructive pulmonary disease, active upper gastrointestinal bleed, or gastric/duodenal ulcer if not on acid-blocking agent) * Informed that taking donepezil is medically inadvisable * Current use of any anticholinergic medication (e.g., for bladder spasm)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Physical Function (Measured by the FIM-motor) | Measured at weeks 0 and 12 | Score on Functional Independence Measure (FIM) motor score, where 7 indicates total assistance/complete dependence and 91 is complete independence |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Medication Tolerability | Measured throughout the study | Number of participants who withdrew due to side effects. |
Countries
United States
Participant flow
Recruitment details
40 participants received study medication
Participants by arm
| Arm | Count |
|---|---|
| Galantamine Galantamine for 12 weeks
Galantamine: Participants assigned to receive galantamine will receive 4 mg twice a day for 4 weeks, 8 mg twice a day for the next 4 weeks, and 12 mg twice a day for the remainder of the study. | 13 |
| Donepezil Donepezil for 12 weeks
Donepezil: Participants assigned to receive donepezil will receive 5 mg twice a day for 6 weeks, and then 10 mg twice a day for the next 6 weeks. | 13 |
| Total | 26 |
Baseline characteristics
| Characteristic | Donepezil | Galantamine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 13 Participants | 13 Participants | 26 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 69.1 years STANDARD_DEVIATION 6.4 | 69.9 years STANDARD_DEVIATION 7.5 | 69.5 years STANDARD_DEVIATION 7 |
| Region of Enrollment United States | 13 participants | 13 participants | 26 participants |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 8 Participants | 10 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Physical Function (Measured by the FIM-motor)
Score on Functional Independence Measure (FIM) motor score, where 7 indicates total assistance/complete dependence and 91 is complete independence
Time frame: Measured at weeks 0 and 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Galantamine | Physical Function (Measured by the FIM-motor) | Baseline FIM | 47.1 units on a scale | Standard Deviation 9.7 |
| Galantamine | Physical Function (Measured by the FIM-motor) | Week 12 FIM | 73.1 units on a scale | Standard Deviation 16.5 |
| Donepezil | Physical Function (Measured by the FIM-motor) | Baseline FIM | 49.4 units on a scale | Standard Deviation 8.34 |
| Donepezil | Physical Function (Measured by the FIM-motor) | Week 12 FIM | 87.4 units on a scale | Standard Deviation 5.2 |
Secondary
Medication Tolerability
Number of participants who withdrew due to side effects.
Time frame: Measured throughout the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Galantamine | Medication Tolerability | 5 participants |
| Donepezil | Medication Tolerability | 5 participants |