# A Proof of Concept Trial of a Sirtuin-NAD+ Activator in Alzheimer's Disease

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $229,495

## Abstract

Summary
The primary aim of this 90-day randomized trial in older adults with Alzheimer's Disease and mild dementia will
determine whether nicotinamide mononucleotide (NMN), a NAD+ precursor, crosses the blood-brain barrier,
and engages the hypothesized target mechanism. We hypothesize that βNMN administration will cross the
blood-brain barrier and increase brain NAD+ concentrations. This application for administrative supplement
requests funds to support the addition of a second clinical trial site to expedite participant recruitment and
enable the completion of the trial and accomplishment of the proposed aims of the project.
This request for supplemental funds was necessitated by the delay in trial's completion due to multiple
unanticipated factors that included: 1) longer than expected time for securing Food and Drug Administration's
approval of the IND; 2) longer than expected time for IRB review of the study protocol; 3) unanticipated
mechanical problems with the head coil required for the 7T magnetic resonance spectroscopy which delayed
trial's initiation; 4) reluctance of the many participants to undergo lumbar puncture for the collection of the
cerebrospinal fluid; 5) participants excluded because of ineligibility for lumbar puncture or 7T MRS; 6) a large
number of competing AD trials in the Boston metropolitan area; and 7) in the wake of the COVID pandemic,
many older adults, especially those with AD, have been reluctant to come into a healthcare facility for research
studies. To overcome these barriers and expedite enrollment, we have made several changes in the study
protocol with the approval of the DSMB, IRB, and program staff; added a recruiter at BWH; and plan to add a
second trial site at Beth Israel Deaconess Medical Center (BIDMC) under the leadership of Dr. Daniel Press,
an NIH-funded investigator and cognitive neurologist with expertise in conducting AD clinical trials. We plan to
continue to randomize an average of 1 participant each month at the BWH site and will have enrolled an
additional 9 participants at the BWH site. The BIDMC site also will enroll one participant per month for a total of
8 subjects over the next 8 months. This should enable us to complete the enrollment by August 31, 2024, with
the last participant completing the intervention by November 30, 2024. The data clean-up, data-lock, analyses
and preparation of the primary manuscript will take an additional 4 months. We will request a no cost extension
for one year. We are requesting supplemental funds to support the trial activities at BIDMC site and a nominal
additional effort (7.5%) for the Project Manager for project coordination and additional administrative and
reporting tasks. This planned addition of a second trial site has been discussed and approved by the trial's
DSMB and the program staff. The cost saving associated with fewer laboratory tests, procedures, and subject
payments due to fewer subjects having been enrolled will be carried forward to s...

## Key facts

- **NIH application ID:** 10990578
- **Project number:** 3R01AG071074-03S1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** SHALENDER BHASIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $229,495
- **Award type:** 3
- **Project period:** 2021-08-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10990578

## Citation

> US National Institutes of Health, RePORTER application 10990578, A Proof of Concept Trial of a Sirtuin-NAD+ Activator in Alzheimer's Disease (3R01AG071074-03S1). Retrieved via AI Analytics 2026-06-13 from https://api.ai-analytics.org/grant/nih/10990578. Licensed CC0.

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