Pilot Studies for the Spectrum of Alzheimer’s Disease/Alzheimer’s Disease-Related Dementias and Age-Related Cognitive Decline (R61 Clinical Trial Optional)

PAR-21-360

This FOA invites research grant applications that enable the collection of pilot data to support early stage testing of promising pharmacological and non-pharmacological interventions that target deleterious cognitive and neuropsychiatric changes associated with age-related cognitive decline and AD/ADRD across the spectrum from pre-symptomatic to more severe stages of disease. Pilot data should be focused on addressing issues of feasibility, safety, and tolerability/acceptability. Furthermore, these data should inform aspects of subject selection, design, and endpoints of subsequent trials. The goal of these pilot data is to serve as preliminary data for applications to the early stage and late stage clinical trial PAR-21-359 .

A recent evidence review conducted by the Agency for Healthcare Research and Quality (AHRQ) on “Care Interventions for People Living With Dementia and Their Caregivers” underscored the need for rigorous, well-powered, replicable research addressing issues of intervention fidelity and efficacy, as well as potential intervention mechanisms. While this review was limited to dementia care and caregiver interventions, the issues identified have relevance to all non-pharmacological (including behavioral and social) clinical trials addressing issues related to AD care, treatment and prevention. Two issues that were highlighted in the AHRQ report were the need to identify how and why interventions work (i.e., the mechanism of action of non-pharmacological (e.g. behavioral) interventions), and the need to ensure that complex interventions can be delivered with fidelity in “real world” settings. The NIH Stage Model is a conceptual framework for intervention development that directly addresses these two issues by: 1) offering a mechanisms-focused framework to intervention development and testing, with the goal of producing interventions defined by their principles and; 2) addressing issues related to ultimate implementation, such as determining ways to ensure that interventions can be delivered in the community with fidelity.

This FOA encourages applications including, but not limited to, the following:

• Studies to refine the intervention strategy. These studies could include work to determine appropriate dosage of drugs, duration of treatment, and the delivery system. For non-pharmacological interventions, such work might examine the intensity or duration of therapy required. This can also include modifying an intervention (consistent with its principles) to make it more scalable and testing it to determine if it retains its potency. This can also include the modification and testing of interventions shown to be efficacious in a non-AD/ADRD population, for an AD/ADRD population. For all interventions, the potential synergistic effects of combined interventions could be explored.
• Studies to evaluate the safety and/or efficacy of the intervention(s).
• Studies that elucidate mechanism of action. In some cases, there may be interventions that have some level of demonstrated efficacy (e.g., exercise for age-related cognitive decline), but lack a real understanding of the mechanism of action. Work in this area could use a variety of approaches appropriate to the intervention in order to elucidate the mechanism of action, which could allow both the confirmation of engagement of the intervention target and the potential to optimize the intervention.
• Studies to define and refine the target population and ensure adequate enrollment, protocol adherence and subject retention.
• Studies that address heterogeneity of response. This would include the identification of specific individuals according to genetic profiles, behavioral factors, and/or sociocultural or demographic factors who are more likely or less likely to benefit from the intervention(s). Mediators of the therapeutic intervention such as continued educational opportunities and continued engagement in driving or financial decision-making may facilitate real-life function and should be considered.

Studies to establish/validate trial outcome measures. These measures may include clinical/neuropsychological/behavioral measures, neuroimaging measures, and other biological measures in blood and cerebrospinal fluid.

Application budgets are limited to $325,000 direct costs per year.

Not required

March 04, 2022, June 17, 2022, October 18, 2022

Laurie Ryan, Ph.D., National Institute on Aging (NIA), Telephone: 301-496-9350
Email: ryanl@mail.nih.gov