Acetylcholinesterase Inhibitors to Improve Cognitive Function and Overall Rehabilitation After a Stroke

• Sponsor: University of Pittsburgh (Other)
• Overall Status: Completed
• CT.gov ID: NCT00227994
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 40
• Location: 1
• Arms: 2
• Duration (Months): 23
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

This study will evaluate the effectiveness of treatment with acetylcholinesterase inhibitors in improving cognitive function and overall rehabilitation in elderly stroke survivors.

Condition or Disease	Intervention/Treatment	Phase
Cerebrovascular Accident	Drug: Galantamine; Drug: Donepezil	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Donepezil/ Galantamine in the Treatment of Post-stroke Cognitively Impaired Rehabilitating Elderly
• Study Start Date: Apr 1, 2003
• Actual Primary Completion Date: Jan 1, 2005
• Actual Study Completion Date: Mar 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Galantamine Galantamine for 12 weeks	Drug: 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.; Other Names: Razadyne
Experimental: Donepezil Donepezil for 12 weeks	Drug: 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.; Other Names: Aricept

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Medication Tolerability [Measured throughout the study]

   Number of participants who withdrew due to side effects.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: All
• Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15260

Sponsors and Collaborators

• University of Pittsburgh
• National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Eric J. Lenze, MD, University of Pittsburgh Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eric Lenze, Professor of Psychiatry, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT00227994
• Other Study ID Numbers: K23MH064196-01; K23MH064196-01
• First Posted: Sep 28, 2005
• Last Update Posted: Dec 11, 2017
• Last Verified: Nov 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Eric Lenze, Professor of Psychiatry, University of Pittsburgh: Cholinesterase Inhibitors; Elderly; Stroke; Cognition
• Additional relevant MeSH terms: Stroke; Donepezil; Galantamine

Study Results

Participant Flow

Recruitment Details	40 participants received study medication

Arm/Group Title	Galantamine	Donepezil
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	20	20
COMPLETED	13	13
NOT COMPLETED	7	7

Baseline Characteristics

Arm/Group Title	Galantamine	Donepezil	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	13	13	26
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	13 100%	13 100%	26 100%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.9 (7.5)	69.1 (6.4)	69.5 (7.0)
Sex: Female, Male (Count of Participants)
Female	3 23.1%	5 38.5%	8 30.8%
Male	10 76.9%	8 61.5%	18 69.2%
Region of Enrollment (participants) [Number]
United States	13 100%	13 100%	26 100%

Outcome Measures

1. Primary Outcome

Title	Physical Function (Measured by the FIM-motor)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Galantamine	Donepezil
Arm/Group Description	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.	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.
Measure Participants	13	13
Baseline FIM	47.1 (9.7)	49.4 (8.34)
Week 12 FIM	73.1 (16.5)	87.4 (5.2)

2. Secondary Outcome

Title	Medication Tolerability
Description	Number of participants who withdrew due to side effects.
Time Frame	Measured throughout the study

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Galantamine	Donepezil
Arm/Group Description	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.	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.
Measure Participants	20	20
Number [participants]	5 38.5%	5 38.5%

Adverse Events

Arm/Group Title	Galantamine		Donepezil
Arm/Group Description	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.		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.
All Cause Mortality
	Galantamine		Donepezil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Galantamine		Donepezil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Galantamine		Donepezil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.