Ignite Creation Date:
2024-05-06 @ 1:46 AM
Last Modification Date:
2024-10-26 @ 11:09 AM
Study NCT ID:
NCT01892579
Status:
COMPLETED
Last Update Posted:
2019-09-23
First Post:
2013-06-27
Brief Title:
Reducing Agitation in People With Dementia the Customized Activity Trial
Sponsor:
Johns Hopkins University
Organization:
Johns Hopkins University
Study Overview
Official Title:
Reducing Agitation in People With Dementia the Customized Activity Trial
Status:
COMPLETED
Status Verified Date:
2019-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
TAP
Brief Summary:
Over 5 million Americans have Alzheimers disease or a related dementia a progressive and irreversible neurodegenerative condition affecting also close to 15 million family caregivers CG A hallmark of the disease and one of the most significant challenges in dementia care is neuropsychiatric symptoms NPS of which agitation is the most disabling and frequently occurring It is associated with increased health care costs reduced life quality heightened caregiver burden disease acceleration and nursing home placement Treatment typically involves pharmacologic agents however these are at best modestly effective carry serious risks including mortality and may not reduce family distress Recently issued position statements from medical organizations suggest nonpharmacologic strategies as first-line treatment Nevertheless nonpharmacological strategies for agitation remain understudied We propose a Phase III efficacy trial to test a novel 8-session patient-centric intervention the Tailored Activity Program We will test the program using a randomized two-group parallel design of 250 people with dementia PwD and their CGs dyads who will be randomly assigned to received a program of tailored activities or a control intervention of equivalent in-home attention and social contact The trial assesses PwDs preserved capabilities deficits previous roles habits interests and home environment from which activities are developed to match PwD profiles Families are trained to implement activities and modify them for future decline Our primary study aim evaluates the effect of tailored activities at 3 months on agitation Hypothesis PwD in the tailored activity program will have less frequent agitation compared to the control intervention condition Three secondary aims evaluate 1 6-month effects of tailored activities on agitation and quality of life in PwD Hypothesis PwD receiving tailored activities will manifest lower severity scores at 6 months and better quality of life compared to PwD in the control intervention 2 Immediate effects of tailored activities at 3 and 6 months on CG wellbeing and time spent providing care Hypothesis CGs receiving training in tailoring activities will report enhanced wellbeing and less time caregiving compared to the control intervention 3 and 6 months and 3 Cost effectiveness of the Tailored Activity Program expressed as an incremental cost outcome achieved in the form of CG burden reductions and willingness to pay for burden reductions 3 and 6 months Hypothesis Tailoring activities will be cost effective compared to the control intervention at each test occasion Exploratory aims will evaluate treatment effects on psychotropic medication use and other troublesome behaviors if effects differ by cognitive status if CGs receiving the tailored activity program will use activities at 6 months and with what frequency how time gained is spent and if frequencyduration of treatment and activity use affects outcomes If proven efficacious and cost effective the Tailored Activity Program has potential to transform clinical practice by offering a proven nonpharmacologic treatment for agitation of PwDs at home This trial addresses a critical clinical need and public health priority identified by recent legislative activity
Detailed Description:
Over 5 million Americans have Alzheimers disease or a related dementia a progressive and irreversible neurodegenerative condition affecting also close to 15 million family caregivers CG A hallmark of the disease and one of the most significant challenges in dementia care is neuropsychiatric symptoms NPS of which agitation is the most disabling and frequently occurring It is associated with increased health care costs reduced life quality heightened caregiver burden disease acceleration and nursing home placement Treatment typically involves pharmacologic agents however these are at best modestly effective carry serious risks including mortality and may not reduce family distress Recently issued position statements from medical organizations suggest nonpharmacologic strategies as first-line treatment Nevertheless nonpharmacological strategies for agitation remain understudied We propose a Phase III efficacy trial to test a novel 8-session patient-centric intervention the Customized Activity Program CAP We will test CAP using a randomized two-group parallel design of 250 people with dementia PwD and their CGs dyads who will be randomly assigned to CAP or a control intervention of equivalent in-home attention and social contact CAP assesses PwDs preserved capabilities deficits previous roles habits interests and home environment from which activities are developed to match PwD profiles Families are trained to implement activities and modify them for future decline A pilot phase with 60 dyads showed clinically meaningful and statistically significant reductions in agitation with no adverse effects Our primary study aim evaluates the effect of CAP at 3 months on agitation Hypothesis PwD in TAP will have lower caregiver rated agitation compared to the control intervention condition Three secondary aims evaluate 1 6-month effects of TAP on agitation and quality of life in PwD Hypothesis PwD in CAP will manifest lower caregiver rated subscale frequency and severity scores at 6 months and better quality of life compared to PwD in the control intervention 2 Immediate effects of CAP at 3 and 6 months on CG wellbeing and time spent providing care Hypothesis CGs receiving CAP will report enhanced wellbeing and less time caregiving compared to the control intervention 3 and 6 months and 3 Cost effectiveness of CAP expressed as an incremental cost outcome achieved in the form of CG burden reductions and willingness to pay for burden reductions 3 and 6 months Hypothesis CAP will be cost effective compared to the control intervention at each test occasion Five exploratory aims will evaluate treatment effects on psychotropic medication use and other troublesome behaviors if effects differ by cognitive status if CGs receiving CAP use activities at 6 months and with what frequency how time gained is spent and if frequencyduration of treatment and activity use affects outcomes If proven efficacious and cost effective CAP has potential to transform clinical practice by offering a proven nonpharmacologic treatment for agitation of PwDs at home This trial addresses a critical clinical need and public health priority identified by recent legislative activity
Objectives
Our primary study aim evaluates the immediate effect of CAP on agitation at 3 months Our hypothesis is that PwD receiving CAP will manifest a lower caregiver rated frequency and severity score on the Neuropsychiatric Inventory-NPI subscales of agitationaggression 21 items compared to those in the control intervention
Three secondary aims are to evaluate 1 effects of CAP at 6 months on agitation and quality of life in patients Hypothesis Patients receiving CAP will manifest lower caregiver rated frequency and severity scores on the NPI-C agitation aggression subscales and better quality of life in comparison to patients receiving the control intervention from baseline to 6 months 2 effects of CAP at 3 and 6 months on CG wellbeing burden skill acquisition efficacy using activities and time spent providing care Hypothesis Caregivers receiving CAP will report enhanced wellbeing and less time caregiving compared to those in the control intervention at 3 and at 6 months and 3 cost effectiveness of CAP expressed as an incremental cost outcome achieved in the form of CG burden reductions and willingness to pay for burden reductions at 3 and 6 months Hypothesis CAP will be cost effective compared to the control intervention at each test occasion
To further understand treatment effects and enhance translation we propose exploratory aims to evaluate 1 Impact of CAP on psychotropic medication use in treatment and control conditions at 3 and 6 months by comparing proportion of PwD who require dose increases or incident use of psychotropic medications negative outcome and proportion of PwD who reduce or eliminate medication use because agitation improved positive outcome 2 Whether treatment effect on agitation differs at 3 and 6 months by cognitive status 3 Whether CAP reduces total NPI scores as rated by CGs at 3 and 6 months 4 If at 6-months CGs receiving CAP are using prescribed activities and with what frequency and how CGs use any personal time gained and 5 Extent to which treatment receipt and enactment frequencyduration of sessions and use of activities affects NPI-C scores If proven efficacious and cost effective CAP has potential to transform the current paradigm of dementia care that relies primarily on the pharmacologic management of agitation It will offer clinicians and families a proven nonpharmacologic approach to enhance quality of life that can be replicated has reimbursement potential and resonates with medical treatment guidelines and health care reform efforts aimed at reducing pharmacologic use and helping older adults be cared for at home
Background
This proposed trial specifically builds upon and extends the pilot phase testing of the proposed intervention with 60 dyads NIMH R21 grant R21 MH069425 This pilot phase evaluated program acceptability identified behaviors most responsive and evaluated magnitude of change for NPS and CG burden Dyads were interviewed at baseline randomized to intervention or wait-list control and then reassessed at 4-months After 4-months the wait-list control group received the intervention and was reevaluated at 8 months within group comparison 4 to 8 months Main outcomes At 4-months a statistically significant treatment effect was found for frequency of NPS overall p010 Cohens d72 using the 16-item Agitated Behavior Inventory for dementia Specifically 77 of CGs in treatment reported improvements in NPS compared to 40 in the wait-list group 23 in treatment reported worsening of NPS compared to 60 in wait-lists As untreated agitation worsens over time in a significant proportion of patients our pilot data suggests that worsened agitation was less common in the intervention group the intervention also appeared to help reduce likelihood of worsening in patients whose agitation was destined to worsen without treatment It appears unlikely that the intervention caused an adverse effect of worsening However as this is a possibility it is listed in the consent form as a possible risk Reductions for intervention group also occurred for specific behaviors reflecting agitation and behaviors of most concern to this CG sample shadowing p003 Cohens d310 and repetitive questioning p023 Cohens d122 with slight increases worsening found for the control group As shown in Figure 2 we also found a statistically significant reduction in prevalence of caregivers reporting agitation p014 Cohens d75 148 in treatment vs 448 in control reported PwD agitation at 4 months A similar pattern was found for argumentation p010 Cohens d77 Also CG in treatment reported that PwD demonstrated better engagement p029 Cohens d61 more pleasure p045 Cohens d690 and improved ability to keep positively busy p017 Cohens d71 Equally significant were reductions in CG objective burden as measured by NIH REACH vigilance items hours doing things for PwD p005 Cohens d114 and hours on duty p001 Cohens d101 with those in intervention reporting 5 hours less and those in control reporting spending 3 hours more on duty Control group participants demonstrated similar benefits from 4 to 8 months Medication Use Of 60 PwD 783 were on an anti-dementia medication cholinesterase inhibitor or memantine 32 were on psychotropic medication for NPS and 45 were on antidepressants at study entry Use of medications did not impact the primary outcome eg frequency of behavioral symptoms In separate regression analyses we entered baseline usenon-use of 3 medication-types eg anti-depressant other psychotropic medication and anti-dementia medications as a predictor and found no impact on treatment outcome or effect size This shows that medications are common yet NPS persist It also suggests the importance of assuring that PwD are on a stabilized dose prior to entering a trial so that treatment effects are not confounded by medication use Cognitive Status We found no difference in treatment effect by cognitive status both high 10 and low 10 MMSE groups benefited similarly with regard to the reduction of behavioral frequency However the high MMSE group also showed a reduction in the number of behaviors occurring at 4 months p028 Cost We also calculated preliminary incremental cost-effectiveness ratios ICER expressed as cost to bring about one additional unit of benefit measured by CG hours per day doing things and hours per day being on duty and decision tree and Monte Carlo analyses tested robustness of economic models Average intervention cost was 94163 per dyad ICER showed that CGs in treatment saved one extra hour per day doing things at a cost of 237 per day and one extra hour per day being on duty at a cost of 110 per day Monte Carlo showed that the intervention was cost-effective 792 of the time for doing things and 796 of the time for being on duty Varying cost assumptions did not change cost-effectiveness In summary this pilot phase demonstrated proof of concept high acceptability by PwD and CGs preliminary positive outcomes preliminary cost effectiveness and that benefits were for PwD agitation and no adverse events It also provides guidance for trial design considerations including importance of assuring dyads on medications have a stabilized dose prior to study enrollment and evaluating relationship of cognitive status to outcomes Our proposed trial advances this pilot phase by a testing efficacy with a larger diverse sample that will be well characterized as to diagnosis disease severity and behaviors using standard clinical assessments b comparing CAP to a control intervention condition receiving equivalent attention and social contact controlling for unknown effects of empathy validation and attention provided in CAP c examining cost effectiveness prospectively from a societal perspective and d evaluating a broad range of other outcomes and moderators dose intensity activity use to support future translational efforts
Objectives
Our primary study aim evaluates the immediate effect of CAP on agitation at 3 months Our hypothesis is that PwD receiving CAP will manifest a lower caregiver rated frequency and severity score on the Neuropsychiatric Inventory-NPI subscales of agitationaggression 21 items compared to those in the control intervention
Three secondary aims are to evaluate 1 effects of CAP at 6 months on agitation and quality of life in patients Hypothesis Patients receiving CAP will manifest lower caregiver rated frequency and severity scores on the NPI-C agitation aggression subscales and better quality of life in comparison to patients receiving the control intervention from baseline to 6 months 2 effects of CAP at 3 and 6 months on CG wellbeing burden skill acquisition efficacy using activities and time spent providing care Hypothesis Caregivers receiving CAP will report enhanced wellbeing and less time caregiving compared to those in the control intervention at 3 and at 6 months and 3 cost effectiveness of CAP expressed as an incremental cost outcome achieved in the form of CG burden reductions and willingness to pay for burden reductions at 3 and 6 months Hypothesis CAP will be cost effective compared to the control intervention at each test occasion
To further understand treatment effects and enhance translation we propose exploratory aims to evaluate 1 Impact of CAP on psychotropic medication use in treatment and control conditions at 3 and 6 months by comparing proportion of PwD who require dose increases or incident use of psychotropic medications negative outcome and proportion of PwD who reduce or eliminate medication use because agitation improved positive outcome 2 Whether treatment effect on agitation differs at 3 and 6 months by cognitive status 3 Whether CAP reduces total NPI scores as rated by CGs at 3 and 6 months 4 If at 6-months CGs receiving CAP are using prescribed activities and with what frequency and how CGs use any personal time gained and 5 Extent to which treatment receipt and enactment frequencyduration of sessions and use of activities affects NPI-C scores If proven efficacious and cost effective CAP has potential to transform the current paradigm of dementia care that relies primarily on the pharmacologic management of agitation It will offer clinicians and families a proven nonpharmacologic approach to enhance quality of life that can be replicated has reimbursement potential and resonates with medical treatment guidelines and health care reform efforts aimed at reducing pharmacologic use and helping older adults be cared for at home
Background
This proposed trial specifically builds upon and extends the pilot phase testing of the proposed intervention with 60 dyads NIMH R21 grant R21 MH069425 This pilot phase evaluated program acceptability identified behaviors most responsive and evaluated magnitude of change for NPS and CG burden Dyads were interviewed at baseline randomized to intervention or wait-list control and then reassessed at 4-months After 4-months the wait-list control group received the intervention and was reevaluated at 8 months within group comparison 4 to 8 months Main outcomes At 4-months a statistically significant treatment effect was found for frequency of NPS overall p010 Cohens d72 using the 16-item Agitated Behavior Inventory for dementia Specifically 77 of CGs in treatment reported improvements in NPS compared to 40 in the wait-list group 23 in treatment reported worsening of NPS compared to 60 in wait-lists As untreated agitation worsens over time in a significant proportion of patients our pilot data suggests that worsened agitation was less common in the intervention group the intervention also appeared to help reduce likelihood of worsening in patients whose agitation was destined to worsen without treatment It appears unlikely that the intervention caused an adverse effect of worsening However as this is a possibility it is listed in the consent form as a possible risk Reductions for intervention group also occurred for specific behaviors reflecting agitation and behaviors of most concern to this CG sample shadowing p003 Cohens d310 and repetitive questioning p023 Cohens d122 with slight increases worsening found for the control group As shown in Figure 2 we also found a statistically significant reduction in prevalence of caregivers reporting agitation p014 Cohens d75 148 in treatment vs 448 in control reported PwD agitation at 4 months A similar pattern was found for argumentation p010 Cohens d77 Also CG in treatment reported that PwD demonstrated better engagement p029 Cohens d61 more pleasure p045 Cohens d690 and improved ability to keep positively busy p017 Cohens d71 Equally significant were reductions in CG objective burden as measured by NIH REACH vigilance items hours doing things for PwD p005 Cohens d114 and hours on duty p001 Cohens d101 with those in intervention reporting 5 hours less and those in control reporting spending 3 hours more on duty Control group participants demonstrated similar benefits from 4 to 8 months Medication Use Of 60 PwD 783 were on an anti-dementia medication cholinesterase inhibitor or memantine 32 were on psychotropic medication for NPS and 45 were on antidepressants at study entry Use of medications did not impact the primary outcome eg frequency of behavioral symptoms In separate regression analyses we entered baseline usenon-use of 3 medication-types eg anti-depressant other psychotropic medication and anti-dementia medications as a predictor and found no impact on treatment outcome or effect size This shows that medications are common yet NPS persist It also suggests the importance of assuring that PwD are on a stabilized dose prior to entering a trial so that treatment effects are not confounded by medication use Cognitive Status We found no difference in treatment effect by cognitive status both high 10 and low 10 MMSE groups benefited similarly with regard to the reduction of behavioral frequency However the high MMSE group also showed a reduction in the number of behaviors occurring at 4 months p028 Cost We also calculated preliminary incremental cost-effectiveness ratios ICER expressed as cost to bring about one additional unit of benefit measured by CG hours per day doing things and hours per day being on duty and decision tree and Monte Carlo analyses tested robustness of economic models Average intervention cost was 94163 per dyad ICER showed that CGs in treatment saved one extra hour per day doing things at a cost of 237 per day and one extra hour per day being on duty at a cost of 110 per day Monte Carlo showed that the intervention was cost-effective 792 of the time for doing things and 796 of the time for being on duty Varying cost assumptions did not change cost-effectiveness In summary this pilot phase demonstrated proof of concept high acceptability by PwD and CGs preliminary positive outcomes preliminary cost effectiveness and that benefits were for PwD agitation and no adverse events It also provides guidance for trial design considerations including importance of assuring dyads on medications have a stabilized dose prior to study enrollment and evaluating relationship of cognitive status to outcomes Our proposed trial advances this pilot phase by a testing efficacy with a larger diverse sample that will be well characterized as to diagnosis disease severity and behaviors using standard clinical assessments b comparing CAP to a control intervention condition receiving equivalent attention and social contact controlling for unknown effects of empathy validation and attention provided in CAP c examining cost effectiveness prospectively from a societal perspective and d evaluating a broad range of other outcomes and moderators dose intensity activity use to support future translational efforts
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R01AG041781 | NIH | None | httpsreporternihgovquickSearchR01AG041781 |