COMET-AD: Comparative Research of Alzheimer's Disease Drugs

• Sponsor: Indiana University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01362686
• Collaborator: Agency for Healthcare Research and Quality (AHRQ) (U.S. Fed)
• Enrollment: 200
• Locations: 5
• Arms: 3
• Duration (Months): 54
• Patients Per Site: 40
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

Conduct a comparative effectiveness clinical trial of medication treatment for behavioral symptoms of Alzheimer's disease in a group of real-world memory care clinics with enhanced access to the Indiana Network for Patient Care.

Condition or Disease	Intervention/Treatment	Phase
Dementia; Alzheimer's Disease	Drug: Donepezil; Drug: Galantamine; Drug: Rivastigmine	N/A

Detailed Description

The overarching goal of this proposal is to enhance the existing information technology infrastructure in Central Indiana to improve the nation's capacity to conduct comparative effectiveness research (CER). Consistent with the instructions in RFA-HS-10-005, the investigators propose to apply these new capacities to a novel CER project evaluating treatment for Alzheimer's disease. Alzheimer's disease has been identified as a first quartile CER priority. This proposal represents collaboration between the Medical Informatics Program at the Regenstrief Institute, Inc (a world leader in health information technology) and two Indiana University research programs: the Center for Aging Research and the Division of Clinical Pharmacology. These programs have an established track record in research relevant to under-served populations. Thus, this proposal combines considerable investigator, environment, and research strengths to continue to build a novel CER infrastructure in support of the nation's evidentiary CER priorities.

Throughout this proposal, the investigators use the AHRQ definition of CER: the conduct and synthesis of research comparing the benefits and harms of different interventions and strategies to prevent, diagnose, treat and monitor health conditions in real world settings." The investigators also refer to a clinical trial of medication treatment for behavioral symptoms of Alzheimer's disease as the specific CER proposed to demonstrate the potential of our new infrastructure. However, the investigators stress that the enhancements proposed to existing infrastructure would support a broad portfolio of CER across an array of priority conditions. The investigators are also proposing enhancements in our privacy and confidentiality technology that would allow researchers from across the country to access de-identified data in support of CER. In summary, the investigators are proposing to add new CER knowledge on Alzheimer' disease and thereby field test new information technology capacities important to a wide range of CER projects while also increasing our capacity to provide data and opportunities for nationwide CER.

The derivation of meaningful and actionable evidence from CER ultimately depends on capturing relevant, comprehensive and accurate data about treatment decisions, patients' clinical status, their care processes and environment, and the health outcomes they experience and value. Such data must be tracked longitudinally in order to determine temporal relationships, cause-effect paradigms, and the efficacy of specific clinical interventions in the context of other conditions, interventions, and goals of care. At Indiana University and the Regenstrief Institute, the investigators have four decades of experience and a well-documented, world-class clinical informatics and research infrastructure for capturing, storing, querying and analyzing treatment patterns and patients' clinical outcomes.

The maturation of this health information technology is now embodied within the Indiana Network for Patient Care (INPC), a fully-operational regional health information exchange. The investigators are well positioned to expand and leverage this infrastructure in support of local and national multi-site clinical trials in comparative effectiveness. The specific aims of this proposal are to:

1.0 PROSPECT STUDY: Enhance our existing information technology infrastructure to:

1. provide de-identified access to the INPC database for CER work

2. capture, store, and track a broader array of health care outcomes important to patients and their caregivers (e.g. behavioral symptoms due to dementia);

3. support providers' and caregivers' and researchers' increasing need to work in teams by providing new tools for communication and co-management (e.g. collaborative care and research)

2.0 COMET-AD STUDY: Conduct comparative effectiveness clinical trial of medication treatment for behavioral symptoms of Alzheimer's disease in a group of real-world memory care clinics with enhanced access to the Indiana Network for Patient Care.

Study Design

• Study Type: Interventional
• Actual Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Comparative Effectiveness Research Trial of Alzheimer's Disease Drugs
• Study Start Date: Apr 1, 2011
• Actual Primary Completion Date: Oct 1, 2015
• Actual Study Completion Date: Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Donepezil See intervention note.	Drug: Donepezil; The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.; Other Names: Aricept
Experimental: Galantamine See intervention note.	Drug: Galantamine; The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.; Other Names: Razadyne
Experimental: Rivastigmine See intervention note.	Drug: Rivastigmine; The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.; Other Names: Exelon

Outcome Measures

Primary Outcome Measures

1. Discontinuation Rates [6, 12, and 18 week interviews from enrollment]

   We are not seeking to establish efficacy of these three medications for the indication of Alzheimer's disease. Each of these medications already has FDA-approval for Alzheimer's. The primary outcome measure is the discontinuation rate among the three medications. Based on previous systematic reviews, these rates are reportedly in the range of 30% by 12 weeks compared with placebo. We will determine the approximate date of discontinuation by self-reports from the caregiver through the telephone-based interview at 6, 12, and 18 weeks.

Secondary Outcome Measures

1. Neuropsychiatric Inventory (NPI) [Baseline, 6, 12, 18 week interviews from enrollment]

   The NPI is based on a structured interview administered to an informal caregiver and has been adopted by the Alzheimer's Disease Cooperative Studies Group to obtain information on the presence of psychopathology in behavioral areas including delusions, apathy, hallucinations, disinhibition, agitation, depression, aberrant motor behavior, anxiety, night-time behavior, and euphoria.9 For each of 12 symptoms, if the caregiver reports the presence of psychopathology, a frequency and severity score are multiplied to yield a possible item score range of 0-12, and a possible total score range of 0-144. The NPI can be used to assess changes in the patient's behavior over the past month. The NPI also assesses the level of caregiver distress attributable to each of the 12 patient behaviors, with a possible total caregiver distress score range of 0-60. Higher scores indicate higher severity of psychopathology and caregiver disress. The NPI has excellent reliability and validity.

2. Healthy Aging Brain Care (HABC)-Monitor [baseline, 6, 12, and 18 week interviews]

   The current HABC-Monitor includes 30 items covering four clinically relevant domains of dementia, ie, cognitive, functional, behavioral, and psychological symptoms, and caregiver quality of life. For brevity and practical use in the clinical setting, each item on the four scales was designed to have the same item response options consisting of four categories that use the frequency of the target problem in the past 2 weeks. The HABC- Monitor took approximately 6 minutes to complete. The scores of the four scales are summed to create the total scores which were used in this analysis.The higher the total score, the higher the level of self reported caregiver burden. The minimum score is 0 and the maximum score is 90.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• older adults with a diagnosis of possible or probable Alzheimer's disease

• planning to initiate treatment with a cholinesterase inhibitor

• planning to continue care in the memory care practice

• participation by a family caregiver willing to complete the study outcome assessments

• access to a telephone

• ability to understand English-Language survey instruments

Exclusion Criteria:

• prior serious adverse event from the study medications

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Touchpoint	Fishers	Indiana	United States	46037
2	Methodist Center for Geriatric Medicine	Indianapolis	Indiana	United States	46202
3	University Clinical Neurology	Indianapolis	Indiana	United States	46202
4	Wishard Health Services	Indianapolis	Indiana	United States	46202
5	St. Vincent Center for Healthy Aging	Indianapolis	Indiana	United States	46260

Sponsors and Collaborators

• Indiana University
• Agency for Healthcare Research and Quality (AHRQ)

Investigators

• Principal Investigator: Malaz Boustani, MD, MPH, Regenstrief Institute, Center for Aging Research

Study Documents (Full-Text)

None provided.

More Information

Publications

• Boustani M, Callahan CM, Unverzagt FW, Austrom MG, Perkins AJ, Fultz BA, Hui SL, Hendrie HC. Implementing a screening and diagnosis program for dementia in primary care. J Gen Intern Med. 2005 Jul;20(7):572-7.
• Boustani M, Healey P, Sennour Y, Munger S. Indianapolis Discovery Network for Dementia. JAGS 2007; 55:S44
• Callahan CM, Boustani MA, Unverzagt FW, Austrom MG, Damush TM, Perkins AJ, Fultz BA, Hui SL, Counsell SR, Hendrie HC. Effectiveness of collaborative care for older adults with Alzheimer disease in primary care: a randomized controlled trial. JAMA. 2006 May 10;295(18):2148-57.
• Campbell N, Boustani M, Limbil T, Ott C, Fox C, Maidment I, Schubert CC, Munger S, Fick D, Miller D, Gulati R. The cognitive impact of anticholinergics: a clinical review. Clin Interv Aging. 2009;4:225-33. Epub 2009 Jun 9. Review.

• Responsible Party: Malaz Boustani, MD, MPH, Regenstrief Institute, IU Center for Aging Reserach Scientist, Regenstrief Institute, Inc.
• ClinicalTrials.gov Identifier: NCT01362686
• Other Study ID Numbers: R01HS019818-01; R01HS019818-01
• First Posted: May 30, 2011
• Last Update Posted: Feb 27, 2017
• Last Verified: Jan 1, 2017

• Keywords provided by Malaz Boustani, MD, MPH, Regenstrief Institute, IU Center for Aging Reserach Scientist, Regenstrief Institute, Inc.: diagnosis of Alzheimer's disease; medication adherence
• Additional relevant MeSH terms: Alzheimer Disease; Rivastigmine; Donepezil; Galantamine

Study Results

Participant Flow

Recruitment Details	Recruitment took place from 2011-2014. Recruitment took place in geriatric and memory care specialty clinics in an urban setting. Registered nurses, nurse practitioners, and research assistants completed the recruitment and informed consent procedures.
Pre-assignment Detail	The enrollment goal in the original protocol of the study was 200 patient-caregiver dyads. 200 were enrolled, but it was discovered that 4 dyads were ineligible after enrollment and were not randomized or included in the study which brings the total enrollment to 196. Recruitment was then terminated due to low enrollment rate.

Arm/Group Title	Donepezil	Galantamine	Rivastigmine
Arm/Group Description	See intervention note. Donepezil: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.	See intervention note. Galantamine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.	See intervention note. Rivastigmine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.
Period Title: Overall Study
STARTED	67	66	63
COMPLETED	59	54	53
NOT COMPLETED	8	12	10

Baseline Characteristics

Arm/Group Title	Donepezil	Galantamine	Rivastigmine	Total
Arm/Group Description	See intervention note. Donepezil: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.	See intervention note. Galantamine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.	See intervention note. Rivastigmine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.	Total of all reporting groups
Overall Participants	67	66	63	196
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	79.1 (7.6)	80.1 (9.6)	81.6 (7.8)	80.2 (8.4)
Gender (Count of Participants)
Female	19 28.4%	20 30.3%	12 19%	51 26%
Male	48 71.6%	46 69.7%	51 81%	145 74%

Outcome Measures

1. Primary Outcome

Title	Discontinuation Rates
Description	We are not seeking to establish efficacy of these three medications for the indication of Alzheimer's disease. Each of these medications already has FDA-approval for Alzheimer's. The primary outcome measure is the discontinuation rate among the three medications. Based on previous systematic reviews, these rates are reportedly in the range of 30% by 12 weeks compared with placebo. We will determine the approximate date of discontinuation by self-reports from the caregiver through the telephone-based interview at 6, 12, and 18 weeks.
Time Frame	6, 12, and 18 week interviews from enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Donepezil	Galantamine	Rivastigmine
Arm/Group Description	See intervention note. Donepezil: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.	See intervention note. Galantamine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.	See intervention note. Rivastigmine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.
Measure Participants	67	66	63
Number [participants]	26 38.8%	35 53%	37 58.7%

2. Secondary Outcome

Title	Neuropsychiatric Inventory (NPI)
Description	The NPI is based on a structured interview administered to an informal caregiver and has been adopted by the Alzheimer's Disease Cooperative Studies Group to obtain information on the presence of psychopathology in behavioral areas including delusions, apathy, hallucinations, disinhibition, agitation, depression, aberrant motor behavior, anxiety, night-time behavior, and euphoria.9 For each of 12 symptoms, if the caregiver reports the presence of psychopathology, a frequency and severity score are multiplied to yield a possible item score range of 0-12, and a possible total score range of 0-144. The NPI can be used to assess changes in the patient's behavior over the past month. The NPI also assesses the level of caregiver distress attributable to each of the 12 patient behaviors, with a possible total caregiver distress score range of 0-60. Higher scores indicate higher severity of psychopathology and caregiver disress. The NPI has excellent reliability and validity.
Time Frame	Baseline, 6, 12, 18 week interviews from enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Donepezil	Galantamine	Rivastigmine
Arm/Group Description	See intervention note. Donepezil: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.	See intervention note. Galantamine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.	See intervention note. Rivastigmine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.
Measure Participants	59	58	54
6 WeekNPI Patient	12.71 (17.10)	9.42 (13.21)	8.63 (11.73)
6 Week NPI Caregiver	5.94 (9.09)	4.40 (5.80)	3.91 (4.86)
12 Week NPI Patient	9.62 (13.56)	8.40 (13.27)	5.24 (5.54)
12 Week NPI Caregiver	5.66 (7.34)	4.33 (6.01)	2.22 (2.86)
18 Week NPI Patient	9.06 (13.87)	10.67 (13.85)	7.26 (7.36)
18 Week NPI Caregiver	5.56 (7.66)	6.22 (7.56)	2.89 (3.17)

3. Secondary Outcome

Title	Healthy Aging Brain Care (HABC)-Monitor
Description	The current HABC-Monitor includes 30 items covering four clinically relevant domains of dementia, ie, cognitive, functional, behavioral, and psychological symptoms, and caregiver quality of life. For brevity and practical use in the clinical setting, each item on the four scales was designed to have the same item response options consisting of four categories that use the frequency of the target problem in the past 2 weeks. The HABC- Monitor took approximately 6 minutes to complete. The scores of the four scales are summed to create the total scores which were used in this analysis.The higher the total score, the higher the level of self reported caregiver burden. The minimum score is 0 and the maximum score is 90.
Time Frame	baseline, 6, 12, and 18 week interviews

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Donepezil	Galantamine	Rivastigmine
Arm/Group Description	See intervention note. Donepezil: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.	See intervention note. Galantamine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.	See intervention note. Rivastigmine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.
Measure Participants	59	58	54
Baseline HABC	18.76 (13.64)	18.34 (11.91)	16.61 (11.49)
6 Week HABC	18.61 (15.16)	19.16 (12.72)	16.43 (10.52)
12 Week HABC	16.04 (13.41)	18.00 (15.71)	13.63 (9.34)
18 Week HABC	16.90 (15.30)	19.92 (14.28)	15.80 (9.01)

Adverse Events

Time Frame	Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.
Arm/Group Title	Donepezil		Galantamine		Rivastigmine
Arm/Group Description	See intervention note. Donepezil: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.		See intervention note. Galantamine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.		See intervention note. Rivastigmine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.
All Cause Mortality
	Donepezil		Galantamine		Rivastigmine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Donepezil		Galantamine		Rivastigmine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/59 (54.2%)		29/54 (53.7%)		27/53 (50.9%)
Cardiac disorders
Fast or Slowed Heart Rate	5/59 (8.5%)	7	0/54 (0%)	0	4/53 (7.5%)	5
Irregular Heart Beat	4/59 (6.8%)	4	3/54 (5.6%)	4	3/53 (5.7%)	3
Gastrointestinal disorders
Diahrrhea	13/59 (22%)	17	5/54 (9.3%)	5	7/53 (13.2%)	8
General disorders
Fainting	2/59 (3.4%)	2	1/54 (1.9%)	1	2/53 (3.8%)	2
Falls	0/59 (0%)	0	0/54 (0%)	0	3/53 (5.7%)	3
Feeling Tired	7/59 (11.9%)	10	5/54 (9.3%)	7	3/53 (5.7%)	3
Incontinence	5/59 (8.5%)	6	6/54 (11.1%)	9	5/53 (9.4%)	6
Metabolism and nutrition disorders
Lack of Interest in Eating	9/59 (15.3%)	10	3/54 (5.6%)	3	4/53 (7.5%)	4
Musculoskeletal and connective tissue disorders
Muscle Cramps	5/59 (8.5%)	7	6/54 (11.1%)	8	3/53 (5.7%)	5
Nervous system disorders
Dizziness	4/59 (6.8%)	4	6/54 (11.1%)	10	8/53 (15.1%)	9
Headache	6/59 (10.2%)	7	4/54 (7.4%)	6	3/53 (5.7%)	4
Pain	3/59 (5.1%)	5	7/54 (13%)	10	4/53 (7.5%)	5
Seizure or Fits	1/59 (1.7%)	1	1/54 (1.9%)	1	0/53 (0%)	0
Psychiatric disorders
Nightmares	6/59 (10.2%)	8	3/54 (5.6%)	5	1/53 (1.9%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	2/59 (3.4%)	2	5/54 (9.3%)	5	2/53 (3.8%)	2
Runny Nose	8/59 (13.6%)	9	5/54 (9.3%)	6	4/53 (7.5%)	4
Other (Not Including Serious) Adverse Events
	Donepezil		Galantamine		Rivastigmine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	40/59 (67.8%)		42/54 (77.8%)		35/53 (66%)
Cardiac disorders
Fast or Slowed Heart Rate	5/59 (8.5%)	6	4/54 (7.4%)	5	0/53 (0%)	0
Irregular Heart Beat	3/59 (5.1%)	4	5/54 (9.3%)	5	1/53 (1.9%)	1
Gastrointestinal disorders
Diahrrhea	11/59 (18.6%)	12	13/54 (24.1%)	16	9/53 (17%)	9
General disorders
Dizziness	13/59 (22%)	14	12/54 (22.2%)	16	9/53 (17%)	9
Fainting	5/59 (8.5%)	6	2/54 (3.7%)	2	1/53 (1.9%)	1
Falls	6/59 (10.2%)	7	5/54 (9.3%)	6	4/53 (7.5%)	4
Feeling Tired	15/59 (25.4%)	21	17/54 (31.5%)	24	14/53 (26.4%)	16
Incontinence	10/59 (16.9%)	14	10/54 (18.5%)	12	9/53 (17%)	13
Metabolism and nutrition disorders
Lack of Interest in Eating	12/59 (20.3%)	12	7/54 (13%)	8	12/53 (22.6%)	15
Musculoskeletal and connective tissue disorders
Muscle Cramps	5/59 (8.5%)	6	6/54 (11.1%)	6	5/53 (9.4%)	10
Nervous system disorders
Headache	4/59 (6.8%)	4	9/54 (16.7%)	10	4/53 (7.5%)	6
Pain	6/59 (10.2%)	6	6/54 (11.1%)	6	6/53 (11.3%)	6
Seizure or Fits	1/59 (1.7%)	2	2/54 (3.7%)	2	0/53 (0%)	0
Psychiatric disorders
Nightmares	7/59 (11.9%)	8	5/54 (9.3%)	7	1/53 (1.9%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	2/59 (3.4%)	2	5/54 (9.3%)	5	2/53 (3.8%)	2
Runny Nose	10/59 (16.9%)	17	13/54 (24.1%)	18	8/53 (15.1%)	9

Limitations/Caveats

Small sample size limits generalizability and may introduce type II error. The study took place at a time when most third-party payers declared donepezil the preferred AChEI due to cost that may have influenced study's results.

More Information

Certain Agreements

Principal Investigators are NOT 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.