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| ID | Type | Description | Link |
|---|---|---|---|
| R01HS019818-01 | U.S. AHRQ Grant/Contract | View source |
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Low study accrual caused the study to be ended early.
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| Name | Class |
|---|---|
| Agency for Healthcare Research and Quality (AHRQ) | FED |
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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.
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Donepezil | Experimental | See intervention note. |
|
| Galantamine | Experimental | See intervention note. |
|
| Rivastigmine | Experimental | See intervention note. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Donepezil | Drug | 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 | Description | Time Frame |
|---|---|---|
| Discontinuation Rates | 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. | 6, 12, and 18 week interviews from enrollment |
| Measure | Description | Time Frame |
|---|---|---|
| Neuropsychiatric Inventory (NPI) | 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. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
• prior serious adverse event from the study medications
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| Name | Affiliation | Role |
|---|---|---|
| Malaz Boustani, MD, MPH | Regenstrief Institute, Center for Aging Research | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Touchpoint | Fishers | Indiana | 46037 | United States | ||
| Methodist Center for Geriatric Medicine |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16684985 | Background | 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. doi: 10.1001/jama.295.18.2148. | |
| 16050849 | Background | 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. doi: 10.1111/j.1525-1497.2005.0126.x. |
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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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Donepezil | 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. |
| FG001 | Galantamine | 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. |
| FG002 | Rivastigmine | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Donepezil | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Discontinuation Rates | 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. | Posted | Number | participants | 6, 12, and 18 week interviews from enrollment |
|
Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Donepezil | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Asthma | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Asthma | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Noll Campbell | Regenstrief Insitute | 317-274-9051 | cambenl@regenstrief.org |
Not provided
| ID | Term |
|---|---|
| D003704 | Dementia |
| D000544 | Alzheimer Disease |
| D055118 | Medication Adherence |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D019965 | Neurocognitive Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077265 | Donepezil |
| D005702 | Galantamine |
| D000068836 | Rivastigmine |
| ID | Term |
|---|---|
| D007189 | Indans |
| D007192 | Indenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Galantamine | Drug | 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. |
|
|
| Rivastigmine | Drug | 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. |
|
|
| Baseline, 6, 12, 18 week interviews from enrollment |
| Healthy Aging Brain Care (HABC)-Monitor | 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. | baseline, 6, 12, and 18 week interviews |
| Indianapolis |
| Indiana |
| 46202 |
| United States |
| University Clinical Neurology | Indianapolis | Indiana | 46202 | United States |
| Wishard Health Services | Indianapolis | Indiana | 46202 | United States |
| St. Vincent Center for Healthy Aging | Indianapolis | Indiana | 46260 | United States |
| 23204843 | Background | Boustani MA, Frame A, Munger S, Healey P, Westlund J, Farlow M, Hake A, Austrom MG, Shepard P, Bubp C, Azar J, Nazir A, Adams N, Campbell NL, Chehresa A, Dexter P. Connecting research discovery with care delivery in dementia: the development of the Indianapolis Discovery Network for Dementia. Clin Interv Aging. 2012;7:509-16. doi: 10.2147/CIA.S36078. Epub 2012 Nov 16. |
| 19554093 | Background | 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. doi: 10.2147/cia.s5358. Epub 2009 Jun 9. |
| 39498781 | Derived | Lim AWY, Schneider L, Loy C. Galantamine for dementia due to Alzheimer's disease and mild cognitive impairment. Cochrane Database Syst Rev. 2024 Nov 5;11(11):CD001747. doi: 10.1002/14651858.CD001747.pub4. |
| 28295141 | Derived | Campbell NL, Perkins AJ, Gao S, Skaar TC, Li L, Hendrie HC, Fowler N, Callahan CM, Boustani MA. Adherence and Tolerability of Alzheimer's Disease Medications: A Pragmatic Randomized Trial. J Am Geriatr Soc. 2017 Jul;65(7):1497-1504. doi: 10.1111/jgs.14827. Epub 2017 Mar 14. |
| 23782591 | Derived | Campbell NL, Dexter P, Perkins AJ, Gao S, Li L, Skaar TC, Frame A, Hendrie HC, Callahan CM, Boustani MA. Medication adherence and tolerability of Alzheimer's disease medications: study protocol for a randomized controlled trial. Trials. 2013 May 4;14:125. doi: 10.1186/1745-6215-14-125. |
| BG001 | Galantamine | 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. |
| BG002 | Rivastigmine | 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. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Gender | Count of Participants | Participants |
|
| OG001 | Galantamine | 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. |
| OG002 | Rivastigmine | 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. |
|
|
| Secondary | Neuropsychiatric Inventory (NPI) | 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. | Posted | Mean | Standard Deviation | units on a scale | Baseline, 6, 12, 18 week interviews from enrollment |
|
|
|
| Secondary | Healthy Aging Brain Care (HABC)-Monitor | 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. | Posted | Mean | Standard Deviation | units on a scale | baseline, 6, 12, and 18 week interviews |
|
|
|
| 32 |
| 59 |
| 40 |
| 59 |
| EG001 | Galantamine | 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. | 29 | 54 | 42 | 54 |
| EG002 | Rivastigmine | 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. | 27 | 53 | 35 | 53 |
| Diahrrhea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | Non-systematic Assessment |
|
| Fainting | General disorders | Non-systematic Assessment |
|
| Falls | General disorders | Non-systematic Assessment |
|
| Fast or Slowed Heart Rate | Cardiac disorders | Non-systematic Assessment |
|
| Feeling Tired | General disorders | Non-systematic Assessment |
|
| Headache | Nervous system disorders | Non-systematic Assessment |
|
| Incontinence | General disorders | Non-systematic Assessment |
|
| Irregular Heart Beat | Cardiac disorders | Non-systematic Assessment |
|
| Lack of Interest in Eating | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Muscle Cramps | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Nightmares | Psychiatric disorders | Non-systematic Assessment |
|
| Pain | Nervous system disorders | Non-systematic Assessment |
|
| Runny Nose | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Seizure or Fits | Nervous system disorders | Non-systematic Assessment |
|
| Diahrrhea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Dizziness | General disorders | Non-systematic Assessment |
|
| Fainting | General disorders | Non-systematic Assessment |
|
| Falls | General disorders | Non-systematic Assessment |
|
| Fast or Slowed Heart Rate | Cardiac disorders | Non-systematic Assessment |
|
| Feeling Tired | General disorders | Non-systematic Assessment |
|
| Headache | Nervous system disorders | Non-systematic Assessment |
|
| Incontinence | General disorders | Non-systematic Assessment |
|
| Irregular Heart Beat | Cardiac disorders | Non-systematic Assessment |
|
| Lack of Interest in Eating | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Muscle Cramps | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Nightmares | Psychiatric disorders | Non-systematic Assessment |
|
| Pain | Nervous system disorders | Non-systematic Assessment |
|
| Runny Nose | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Seizure or Fits | Nervous system disorders | Non-systematic Assessment |
|
Not provided
Not provided
| D001523 | Mental Disorders |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D010349 | Patient Compliance |
| D010342 | Patient Acceptance of Health Care |
| D000074822 | Treatment Adherence and Compliance |
| D015438 | Health Behavior |
| D001519 | Behavior |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D047151 | Amaryllidaceae Alkaloids |
| D000470 | Alkaloids |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D048448 | Phenylcarbamates |
| D002219 | Carbamates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
|
| 12 Week NPI Patient |
|
| 12 Week NPI Caregiver |
|
| 18 Week NPI Patient |
|
| 18 Week NPI Caregiver |
|
|
| 12 Week HABC |
|
| 18 Week HABC |
|