NIH – Pragmatic Trials of Managing Multimorbidity in Alzheimer’s Disease (R61/R33 Clinical Trial Required)

May 13, 2019 by


This Funding Opportunity Announcement (FOA) invites applications proposing to conduct research involving pragmatic clinical trials into improving the effectiveness of treatment strategies for comorbid conditions that occur frequently in combination with Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD). The research will: (1) be designed to address practical comparative questions faced by AD/ADRD patients and clinicians, (2) include broad and diverse populations, and (3) be conducted in real-world settings. These trials are intended to produce results that can be directly adopted by healthcare systems for rapid translation.

This FOA will support pilot research to test the feasibility of implementing care interventions (R61 phase) that, if successful, can transition to an R33 phase for implementation of large pragmatic trials.

The transition from the R61 phase to the R33 phase of the award will be administratively reviewed and determined by successful completion of the Go/No-Go Criteria that are specified for the R61 phase.


Multimorbidity, or having two or more chronic conditions, is a complex challenge for patients, doctors, and healthcare systems. This challenge becomes even more complex when treating patients with Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRD), as the clinical presentation and prolonged course of AD/ADRD influence the diagnosis and treatment of comorbid illness. Compared to patients with other long-term disorders, those with dementia may have extreme multimorbidity, averaging four additional chronic medical disorders. The most common chronic comorbid conditions for AD/ADRD patients are hypertension and diabetes, but other significant comorbidities include, but are not limited to, heart disease, heart failure, obstructive lung disease, and incontinence, as well as acute conditions like infectious diseases and hip fracture.

Dementia can be characterized as a clinically dominant multimorbidity, meaning that it is so serious that it overshadows the management of other health problems. The presence of multimorbidity in patients with dementia has been associated with accelerated functional decline and other adverse outcomes. Furthermore, certain medical comorbidities can exacerbate cognitive and mental deterioration in persons with dementia. Consensus-based diabetes treatment guidelines suggest relaxed glucose control for persons with cognitive impairment, dementia, complex illness, or poor health. Most other treatment guidelines, however, focus on a single disease and lack such detailed recommendations, likely reflecting a lack of evidence of the balance of risks and benefits in AD/ADRD patients with comorbidities, or perhaps lack of a professional consensus. Although self-management approaches may be appropriate in early stages, throughout the course of dementia family members increasingly assume the role of caregivers to provide the first line of support for treatment.

Some groups have been working toward guidelines for dementia care practice which would apply across care settings, emphasize person-centered care and quality of life, and recognize that needs may change over time. These groups also emphasize that the complex care needs are attributable to both the dementia and the multimorbidity, the potential effectiveness of non-pharmacological interventions for symptoms, and that selective discontinuation of therapies may be beneficial.

This is a continuation of past initiatives released as RFA-AG-17-059 and RFA-AG-18-028, which have led to funding of pragmatic trials on relevant topics, including diabetes management in AD/ADRD and deprescribing potentially inappropriate medications for persons with ADRD. However, there is still a considerable need for research in this area, and this FOA is using a different mechanism for two-stage pragmatic trials. Phase 1 is for trial planning and feasibility, and Phase 2 is for the conduct of the pragmatic trial in health systems

For the R61 planning phase, the combined budget for direct costs for up to two years may not exceed $500,000.

For the R33 phase, budgets are expected to go over $500,000.

Key Dates

Posted Date – May 9, 2019
Open Date (Earliest Submission Date) – January 03, 2020
Letter of Intent Due Date(s) – January 3, 2020
Application Due Date(s) – February 3, 2020, by 5:00 PM local time
Link for more information

Filed Under: Funding Opportunities