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Related Announcements

PAS-22-197 - Advancing Research on Alzheimer's Disease (AD) and AD-Related Dementias (ADRD) (R41/R42 Clinical Trial Optional)

NOT-NS-23-049 - Notice of NINDS Specific Interest in AD/ADRD for PAS-22-196 "Advancing Research on Alzheimer's Disease (AD) and AD-Related Dementias (ADRD) (R43/R44 Clinical Trial Optional)"

Issued by

National Institute of Neurological Disorders and Stroke (NINDS)

Purpose

The purpose of this notice is to add NINDS-specific research interests in PAS-22-197 "Advancing Research on Alzheimer's Disease (AD) and AD-Related Dementias (ADRD) (R41/R42 Clinical Trial Optional)".

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Recommendations and milestones for Alzheimer's disease (AD) and AD-related dementias (ADRD) research from the National Alzheimer’s Project Act and the 2015, 2018, 2019, and 2021 Alzheimer's Disease Research Summits present a wide range of research and development proposals which, if pursued, have the potential to reduce the human burden and healthcare costs associated with AD/ADRD.

As part of the National Institute on Aging's (NIA) strategic plan to support the development of innovative strategies and therapies to prevent, diagnose, and treat AD/ADRD, this Funding Opportunity Announcement (FOA)  invites applications to NIA's Small Business Innovation Research (SBIR) program. The aim of this FOA is to encourage research on, and the commercialization of, novel therapies, devices, products, and healthcare programs and practices to prevent the onset of AD/ADRD, and to reduce the burden that AD/ADRD places on individuals, their families, and society at large.

Examples of research areas of interest include, but are not limited to, the following:

Prevention:

• Behavioral, environmental, pharmacological, and nutritional interventions to prevent and/or remediate brain biochemical and/or neurophysiological changes caused by neurodegenerative diseases, including age-related sensory dysfunction, motor dysfunction, or age-related decrements in balance and postural control, gait performance, and mobility.
• Programs to support cognitive training to improve cognitive function in the elderly. Examples of topics appropriate for such programs include, but are not limited to, the following:
  • Rapid development of novel, engaging, computer-based cognitive-training programs based on empirically-established approaches using cognitive training to target a specific neural system/functional domain;
  • Augmentation of existing computerized cognitive interventions that can be individually tailored to engage, adapt, challenge, and optimize functional cognitive abilities to enhance cognitive functioning and performance of activities of daily living; and
  • Development of interventions to remediate age-related cognitive decline, especially using technology platforms with wide acceptance among older adults.

Diagnosis:

• Sensitive, specific, and standardized tests for diagnostic screening of mild cognitive impairment (MCI) and dementia, including the development of new, cost-effective, minimally-invasive biomarkers that could be used for screening in the general population and in community settings. In addition, this FOA encourages research that would identify new biomarkers that could serve as surrogate measures for disease progression in AD/ADRD. Other advances might include the development of new instrumentation, imaging technology, related devices, and software packages for use in visualizing neural activity during cognitive, emotional, motor, or sensory behavior in older adults.
• Biosensors and prosthetic devices, technologies, and related software development to aid in the assessment, diagnosis, and remediation of age-related cognitive decline.
• Machine-learning tools and cognitive batteries that can be integrated into Electronic Medical Records (EMR) for diagnosis of MCI and AD/ADRD.
• New approaches for the assessment of persons living with multiple chronic conditions in clinical practice, including development and validation of brief cognitive-screening measures.

Treatment:

• Discovery, development, and/or evaluation of drugs and/or biological or natural products, including central nervous system delivery systems, to remediate age-related cognitive decline and treat the cognitive impairment and/or behavioral symptoms associated with MCI, AD/ADRD, and other dementias of aging. In addition, this FOA invitess research on therapies that might slow and/or reverse the course of AD/ADRD, or prevent them entirely through the application of systems-biology and systems-pharmacology approaches. Therapeutics addressing novel targets are of particular interest.
• Clinical trials to test the safety and efficacy of drug, nutritional, behavioral, cognitive, or other types of interventions to remediate age-related cognitive decline and treat cognitive impairment and/or behavioral symptoms associated with MCI, AD/ADRD, and other dementias of aging, as well as to slow and/or reverse the course of AD/ADRD or to prevent their onset.

Care:

• New technologies for in-home use, or for coordination or delivery of services to sustain in-home living for individuals living with MCI or AD/ADRD. Examples include, but are not limited to, the following:
  • Systems and devices to evaluate, monitor, improve, or adapt to changes in cognition;
  • Improvements in health-service delivery;
  • Improvements in the preservation of functional independence;
  • Technologies supporting independent living and the conduct of everyday tasks at home;
  • Provision of information to healthcare providers and family members enabling assessment of patient needs and/or intervention(s); and
  • Promotion of effective communication and interaction between individuals living with dementia in the community or in institutional settings and their healthcare providers, friends, and family members.
• Assistive robotics technology that can support a person in order to maintain or improve their independence, safety, and well-being when diagnosed with AD/ADRD and alleviate the burden of care. Such efforts might include the development of socially-assistive robots that can support engagement, social participation, and leisure activities of patients living with MCI and AD/ADRD.
• Cost-effective technology to create dementia-friendly cities and environments for individuals diagnosed with AD/ADRD. This might include the development of alarm technology and tracking and location-monitoring devices to alert caregivers and others of the whereabouts of individuals living with AD/ADRD. Other advances might include innovative research to develop safer home environments, such as automatic shut-off valves for water (e.g. a sink could overflow when one forgets to turn off faucet) and electricity and gas (e.g. forgetting to turn off stove).
• Comprehensive telecare systems that can be used to support independence and personal safety of an individual living with AD/ADRD and other dementias. Such telecare systems might include community alarms, medication reminders, sensors for floods or extreme temperatures, detection of absence from normal activities (e.g. sitting in a chair, going to bed), fall detection, and unobtrusive sensors to monitor activities of daily living and vital signs that can be reported to a healthcare provider. Other advances might include the development of technology that would allow for in-place monitoring of individuals at all stages of AD/ADRD. Ideally, such information would be integrated with other patient-relevant data in EMR.
• Wearable, mobile, or other technology to enable direct, objective, and continuous data capture of everyday functions in individuals living with AD/ADRD.
• Recent reviews of relevant scientific literature revealed the presence of disparities of care between diverse racial and ethnic minority populations of individuals with AD/ADRD. To address such disparities, this FOA encourages research to develop educational training programs for physicians, nursing assistants, home-care aids, and long-term-care services. These programs would focus on training healthcare staff to provide culturally-appropriate care to the patient at the right time and in the right setting.

Tools:

• Novel technologies to monitor, assist, or maintain daily functioning of older individuals living with AD/ADRD and other cognitive impairments.
• Manuals and training materials for existing evidence-based interventions that reduce the burden of caregiving for AD/ADRD caregivers which can be used by community-based agencies and/or healthcare organizations.
• A tool that could be sold to Medicare Advantage (MA) plans to allow them to accurately project future costs of caring for patients living with AD/ADRD and other forms of dementia. Such a tool would be based on incidence and cost data and would be capable of being tailored for use by participating MA plans to address the unique demographics and risk characteristics of its coverage pool.
• Technology and analytical tools to investigate genetic, epigenetic, transcriptomic, proteomic, metabolomic, and cell stress pathways in neurons and glia of the aging and AD/ADRD brain. Such efforts might include the development of molecular-imaging technology and/or chip-based technology for in-vitro and in-vivo analysis of gene, epigenome, proteostasis, lipidomics, and metabolomics and metabolic function in the normal aging brain and in AD/ADRD.
• Improved technology for the analysis of structural and functional brain connectivity at the cell, neural circuitry, and global network levels to define the trajectory of changes in brain structure and function in aging and AD/ADRD. Such technology might include the development of non-invasive methods and novel probes that monitor and manipulate the plasticity of neural circuits in the adult and aged nervous system. Further advances might include the development of novel markers of neural stem-cell function (e.g., proliferation, migration, and differentiation) as well as methods to assess the integration and function of stem cells in the aging and/or diseased nervous system.
• Chip-based tools modeling human AD/ADRD for applications in AD/ADRD drug screening and development. Development of novel therapeutics for the treatment of AD/ADRD has proven to be a lengthy, costly, and relatively unproductive process, with drug attrition rates of over 90%. Several studies have indicated the lack of appropriate preclinical AD/ADRD models as one of the barriers for successful development of AD/ADRD therapeutics. Although animal models of AD/ADRD have helped our understanding of AD/ADRD pathogenesis to some extent, key genes and proteins that are critical to the pathogenesis of this disease exhibit many inherent species-specific differences and, consequently, there is a critical need for translation platforms that can accurately and reproducibly mimic the AD/ADRD phenotype in vivo and be amenable to high-content screening and assay applications. Recent advances in stem-cell technology allow for successful generation of human neural-progenitor cells from skin cells of normal and AD/ADRD patients. This technology could be exploited to develop cell-type-specific AD/ADRD disease models by replicating AD/ADRD pathobiology on microfluidic chips. These chips could then provide a novel AD/ADRD model system that could be used in the translation process to:
  • perform high-throughput screening for drug discovery and drug efficacy,
  • develop in situ assays for measuring predictive biomarkers, and
  • validate therapeutic target(s).
• Approaches using artificial intelligence to assist with recruitment and monitoring of study participants for clinical trials of treatments or preventives for AD/ADRD.

Clinical Research Operations Management System

NIA supports a central resource to NIA staff and extramural investigators to facilitate/support the conduct and management of clinical research. This resource, the Clinical Research Operations Management System (CROMS), is a comprehensive data management system to support the business functions, management, and oversight responsibilities of NIA grants that support the conduct of clinical research with human subjects. It is the expectation by NIA that all successful applicants will interface, integrate, or adapt their information system(s) and processes to interact with existing and future components of the CROMS as necessary, including the use of CROMS data templates as specified.

See Section VIII. Other Information for award authorities and regulations.

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

Modified to Read:

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Recommendations and milestones for Alzheimer's disease (AD) and AD-related dementias (ADRD) research from the National Alzheimer’s Project Act and the 2015, 2018, 2019, and 2021 Alzheimer's Disease Research Summits present a wide range of research and development proposals which, if pursued, have the potential to reduce the human burden and healthcare costs associated with AD/ADRD.

As part of the National Institute on Aging's (NIA) strategic plan to support the development of innovative strategies and therapies to prevent, diagnose, and treat AD/ADRD, this Funding Opportunity Announcement (FOA)  invites applications to NIA's Small Business Innovation Research (SBIR) program. The aim of this FOA is to encourage research on, and the commercialization of, novel therapies, devices, products, and healthcare programs and practices to prevent the onset of AD/ADRD, and to reduce the burden that AD/ADRD places on individuals, their families, and society at large.

Examples of research areas of interest include, but are not limited to, the following:

Prevention:

• Behavioral, environmental, pharmacological, and nutritional interventions to prevent and/or remediate brain biochemical and/or neurophysiological changes caused by neurodegenerative diseases, including age-related sensory dysfunction, motor dysfunction, or age-related decrements in balance and postural control, gait performance, and mobility.
• Programs to support cognitive training to improve cognitive function in the elderly. Examples of topics appropriate for such programs include, but are not limited to, the following:
  • Rapid development of novel, engaging, computer-based cognitive-training programs based on empirically-established approaches using cognitive training to target a specific neural system/functional domain;
  • Augmentation of existing computerized cognitive interventions that can be individually tailored to engage, adapt, challenge, and optimize functional cognitive abilities to enhance cognitive functioning and performance of activities of daily living; and
  • Development of interventions to remediate age-related cognitive decline, especially using technology platforms with wide acceptance among older adults.

Diagnosis:

• Sensitive, specific, and standardized tests for diagnostic screening of mild cognitive impairment (MCI) and dementia, including the development of new, cost-effective, minimally-invasive biomarkers that could be used for screening in the general population and in community settings. In addition, this FOA encourages research that would identify new biomarkers that could serve as surrogate measures for disease progression in AD/ADRD. Other advances might include the development of new instrumentation, imaging technology, related devices, and software packages for use in visualizing neural activity during cognitive, emotional, motor, or sensory behavior in older adults.
• Biosensors and prosthetic devices, technologies, and related software development to aid in the assessment, diagnosis, and remediation of age-related cognitive decline.
• Machine-learning tools and cognitive batteries that can be integrated into Electronic Medical Records (EMR) for diagnosis of MCI and AD/ADRD.
• New approaches for the assessment of persons living with multiple chronic conditions in clinical practice, including development and validation of brief cognitive-screening measures.

Treatment:

• Discovery, development, and/or evaluation of drugs and/or biological or natural products, including central nervous system delivery systems, to remediate age-related cognitive decline and treat the cognitive impairment and/or behavioral symptoms associated with MCI, AD/ADRD, and other dementias of aging. In addition, this FOA invitess research on therapies that might slow and/or reverse the course of AD/ADRD, or prevent them entirely through the application of systems-biology and systems-pharmacology approaches. Therapeutics addressing novel targets are of particular interest.
• Clinical trials to test the safety and efficacy of drug, nutritional, behavioral, cognitive, or other types of interventions to remediate age-related cognitive decline and treat cognitive impairment and/or behavioral symptoms associated with MCI, AD/ADRD, and other dementias of aging, as well as to slow and/or reverse the course of AD/ADRD or to prevent their onset.

Care:

• New technologies for in-home use, or for coordination or delivery of services to sustain in-home living for individuals living with MCI or AD/ADRD. Examples include, but are not limited to, the following:
  • Systems and devices to evaluate, monitor, improve, or adapt to changes in cognition;
  • Improvements in health-service delivery;
  • Improvements in the preservation of functional independence;
  • Technologies supporting independent living and the conduct of everyday tasks at home;
  • Provision of information to healthcare providers and family members enabling assessment of patient needs and/or intervention(s); and
  • Promotion of effective communication and interaction between individuals living with dementia in the community or in institutional settings and their healthcare providers, friends, and family members.
• Assistive robotics technology that can support a person in order to maintain or improve their independence, safety, and well-being when diagnosed with AD/ADRD and alleviate the burden of care. Such efforts might include the development of socially-assistive robots that can support engagement, social participation, and leisure activities of patients living with MCI and AD/ADRD.
• Cost-effective technology to create dementia-friendly cities and environments for individuals diagnosed with AD/ADRD. This might include the development of alarm technology and tracking and location-monitoring devices to alert caregivers and others of the whereabouts of individuals living with AD/ADRD. Other advances might include innovative research to develop safer home environments, such as automatic shut-off valves for water (e.g. a sink could overflow when one forgets to turn off faucet) and electricity and gas (e.g. forgetting to turn off stove).
• Comprehensive telecare systems that can be used to support independence and personal safety of an individual living with AD/ADRD and other dementias. Such telecare systems might include community alarms, medication reminders, sensors for floods or extreme temperatures, detection of absence from normal activities (e.g. sitting in a chair, going to bed), fall detection, and unobtrusive sensors to monitor activities of daily living and vital signs that can be reported to a healthcare provider. Other advances might include the development of technology that would allow for in-place monitoring of individuals at all stages of AD/ADRD. Ideally, such information would be integrated with other patient-relevant data in EMR.
• Wearable, mobile, or other technology to enable direct, objective, and continuous data capture of everyday functions in individuals living with AD/ADRD.
• Recent reviews of relevant scientific literature revealed the presence of disparities of care between diverse racial and ethnic minority populations of individuals with AD/ADRD. To address such disparities, this FOA encourages research to develop educational training programs for physicians, nursing assistants, home-care aids, and long-term-care services. These programs would focus on training healthcare staff to provide culturally-appropriate care to the patient at the right time and in the right setting.

Tools:

• Novel technologies to monitor, assist, or maintain daily functioning of older individuals living with AD/ADRD and other cognitive impairments.
• Manuals and training materials for existing evidence-based interventions that reduce the burden of caregiving for AD/ADRD caregivers which can be used by community-based agencies and/or healthcare organizations.
• A tool that could be sold to Medicare Advantage (MA) plans to allow them to accurately project future costs of caring for patients living with AD/ADRD and other forms of dementia. Such a tool would be based on incidence and cost data and would be capable of being tailored for use by participating MA plans to address the unique demographics and risk characteristics of its coverage pool.
• Technology and analytical tools to investigate genetic, epigenetic, transcriptomic, proteomic, metabolomic, and cell stress pathways in neurons and glia of the aging and AD/ADRD brain. Such efforts might include the development of molecular-imaging technology and/or chip-based technology for in-vitro and in-vivo analysis of gene, epigenome, proteostasis, lipidomics, and metabolomics and metabolic function in the normal aging brain and in AD/ADRD.
• Improved technology for the analysis of structural and functional brain connectivity at the cell, neural circuitry, and global network levels to define the trajectory of changes in brain structure and function in aging and AD/ADRD. Such technology might include the development of non-invasive methods and novel probes that monitor and manipulate the plasticity of neural circuits in the adult and aged nervous system. Further advances might include the development of novel markers of neural stem-cell function (e.g., proliferation, migration, and differentiation) as well as methods to assess the integration and function of stem cells in the aging and/or diseased nervous system.
• Chip-based tools modeling human AD/ADRD for applications in AD/ADRD drug screening and development. Development of novel therapeutics for the treatment of AD/ADRD has proven to be a lengthy, costly, and relatively unproductive process, with drug attrition rates of over 90%. Several studies have indicated the lack of appropriate preclinical AD/ADRD models as one of the barriers for successful development of AD/ADRD therapeutics. Although animal models of AD/ADRD have helped our understanding of AD/ADRD pathogenesis to some extent, key genes and proteins that are critical to the pathogenesis of this disease exhibit many inherent species-specific differences and, consequently, there is a critical need for translation platforms that can accurately and reproducibly mimic the AD/ADRD phenotype in vivo and be amenable to high-content screening and assay applications. Recent advances in stem-cell technology allow for successful generation of human neural-progenitor cells from skin cells of normal and AD/ADRD patients. This technology could be exploited to develop cell-type-specific AD/ADRD disease models by replicating AD/ADRD pathobiology on microfluidic chips. These chips could then provide a novel AD/ADRD model system that could be used in the translation process to:
  • perform high-throughput screening for drug discovery and drug efficacy,
  • develop in situ assays for measuring predictive biomarkers, and
  • validate therapeutic target(s).
• Approaches using artificial intelligence to assist with recruitment and monitoring of study participants for clinical trials of treatments or preventives for AD/ADRD.

Clinical Research Operations Management System

NIA supports a central resource to NIA staff and extramural investigators to facilitate/support the conduct and management of clinical research. This resource, the Clinical Research Operations Management System (CROMS), is a comprehensive data management system to support the business functions, management, and oversight responsibilities of NIA grants that support the conduct of clinical research with human subjects. It is the expectation by NIA that all successful applicants will interface, integrate, or adapt their information system(s) and processes to interact with existing and future components of the CROMS as necessary, including the use of CROMS data templates as specified.

National Institute for Neurological Disorders and Stroke (NINDS)

The National Institute for Neurological Disorders and Stroke (NINDS) is interested in applications within the NINDS mission. The small business program at NINDS is used to achieve the mission of the Institute by supporting innovative ideas at different stages of development, including applied bench research, translational research, and early stage clinical trials. NIA and NINDS have shared interest in all areas of AD/ADRD, with NINDS as the lead for Vascular contributions to cognitive impairment and dementia (VCID), Lewy body dementia (LBD), Frontotemporal degeneration (FTD) and Multiple etiology dementias (MED); and NIA as the lead for applications focused on Alzheimer’s Disease.

For those applications that propose a clinical trial and use an FDA-regulated intervention, NINDS will give priority to those applications with (a) A protocol submitted under an open investigational new drug (IND) and the IND is not under full or partial hold. (b) A protocol submitted as an original investigational device exemption (IDE) or as a new study under an open IDE, and FDA has fully approved the IDE or IDE supplement. (c) A protocol submitted under an IND and is on full or partial hold. (d) A protocol submitted as an original IDE or as a new study under an open IDE, and FDA has conditionally approved the IDE or IDE supplement. (e) A protocol is exempt from an IND. (f) A protocol is either exempt from the IDE regulations or does not require IDE approval because it is determined to be nonsignificant risk.

NINDS may decline funding of any application that includes human subjects for programmatic or administrative reasons. STTR applicants considering projects involving human subjects research are strongly encouraged to contact program staff early in the process of preparing a submission.

See Section VIII. Other Information for award authorities and regulations.

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

All other aspects of this FOA remain unchanged.

Inquiries

Please direct all inquiries to:

Annette Gilchrist
National Institute of Neurological Disorders and Stroke (NINDS)
Phone: 301-496-1779
E-mail: Annette.gilchrist@nih.gov