# The LUCINDA Trial

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $1,366,388

## Abstract

Project Summary
This project aims to re-purpose the safe and well-tolerated gonadotropin-releasing hormone (GnRH) analogue
Lupron for use in Alzheimer's Disease (AD). Lupron is currently FDA-approved for prostate cancer,
endometriosis and uterine fibroids in adults and for central precocious puberty in children. We propose to
confirm and extend results from a prior phase II study (Bowen et al, 2015) that demonstrated that Lupron
halted cognitive and functional decline in a subgroup of women with mild-moderate AD who were also taking
an acetylcholinesterase inhibitor (AChEI). Our objectives are to replicate, in the same subgroup, Lupron's
clinical EFFICACY in this prior trial and to add neuroimaging and plasma BIOMARKERS that will help elucidate
Lupron's likely multiple mechanisms of action in AD. These mechanisms include decreasing levels of
Luteinizing Hormone (LH) based on extensive preclinical evidence that decreasing LH preserves cognition and
decreases amyloid deposition and tau phosphorylation in animal models of AD, as well as new evidence that
GnRH analogues may have important anti-inflammatory effects.
We will (1) Conduct a three site, double-blind, randomized trial of Lupron (22.5 mg/12 weeks) compared with
placebo to evaluate the changes over 48 weeks in cognition and function in women with mild-moderate AD
who are also taking a stable dose of AChEI. We hypothesize that patients taking Lupron + AChEI will show a
smaller pre- to post-treatment decline in cognition and function when compared to patients taking placebo +
AChEI. (2) We will assess Lupron’s effect on structural and functional (ASL-MRI) neuroimaging biomarkers of
AD. We hypothesize that patients who receive Lupron + AChEI will demonstrate less atrophy in AD-related
brain regions and preserved hippocampal perfusion as compared to those who receive placebo + AChEI. (3)
We will assess changes in plasma markers of inflammation. We hypothesize that patients taking Lupron +
AChEI, as compared to those taking placebo + AChEI, will show decreased plasma pro-inflammatory
cytokines.
If this second phase II trial of Lupron + AChEI for AD is positive we will proceed to a phase III trial with the goal
of gaining FDA approval for this novel combination therapy for AD. By re-purposing an existing medication, in
combination with a current AD treatment, we will be able to build upon extensive previous research and
development efforts, reducing the time frame and costs of making this promising therapy available to patients
with AD. Results from this project have the potential for significant, near term clinical impact in patients
currently suffering from or at risk of AD.

## Key facts

- **NIH application ID:** 10412901
- **Project number:** 5R01AG057681-04
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Craig S Atwood
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,366,388
- **Award type:** 5
- **Project period:** 2018-08-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10412901

## Citation

> US National Institutes of Health, RePORTER application 10412901, The LUCINDA Trial (5R01AG057681-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10412901. Licensed CC0.

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