Phytoserm efficacy to prevent menopause associated decline in brain metabolism and cognition: a double-blind, randomized, placebo-controlled phase 2 clinical trial

Active Project Grant Awarded Last action

Award ID
R01AG075122
Recipient
Awarding agency
Obligated
$18,872,590

Award facts

Assistance listing
93.866 Aging Research
Completion date 94% complete
Place of performance
Tucson, AZ 85721, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Women are at greater life-time risk for alzheimer's disease (ad). One potential factor contributing to greater life- time risk of ad is the midlife menopausal endocrine aging transition when multiple ad risk conditions can emerge and which are consistent with prodromal / preclinical features of the disease. While estrogen or hormone therapy administered when menopausal women are symptomatic could reduce risk of ad, the fear of breast cancer leads many women to forego this approach. An innovative alternative to estrogen therapy is to target estrogen action in brain while avoiding estrogen-associated proliferation in breast tissue. To achieve that goal, we propose phase 2 clinical development of "phytoserm", a selective estrogen receptor beta (erss) modulator that promotes estrogenic action through erss in brain while inhibitory in reproductive tissue. Phytoserm is a rationally designed formulation of 3 phytoestrogens (each are generally recognized as safe by the FDA). Our earlier NIA supported phytoserm phase 1B/2A clinical trial determined that phytoserm was safe and well-tolerated, exhibited predictive pharmacokinetics in peri- and postmenopausal women and identified responder phenotype (https://clinicaltrials.GOV/CT2/show/NCT01723917). Proposed herein is a phase 2, double-blind, randomized, placebo-controlled, parallel-group, clinical trial to determine efficacy of phytoserm in symptomatic peri- and post-menopausal women. Primary objectives are to determine safety and efficacy of phytoserm to sustain brain glucose metabolism as determined by 18F-FDG- pet because the menopausal transition is accompanied by reduction in cerebral metabolic rate of glucose, which correlates with menopausal symptoms and progression of ad biomarkers later in life. Secondary objectives will determine efficacy of phytoserm on: 1) cognitive function, 2) frequency and severity of vasomotor symptoms and 3) changes in sleep quality and mood symptoms. Tertiary objectives are to determine impact of phytoserm on exploratory MRI outcomes including 1) gray matter volume in ad-vulnerable regions, 2) white matter fiber integrity by diffusion tensor imaging, (3) intrinsic connectivity measured by resting state functional MRI, 4) cerebral blood flow determined by arterial spin labeling (ASL) and 5) blood-based biomarkers relevant to ad risk. The phase 2 phytoserm clinical trial addresses multiple strategic directions of the national institutes on aging's 2020-2025: aging well in the 21ST century REF specifically, goal c-3 to: "develop effective interventions to maintain health, well-being, and function and prevent or reduce the burden of age-related diseases" and "conduct clinical studies / translation of new interventions to the clinical setting." goal d-4: translate basic discovery into effective treatment and/or prevention strategies for ad/adrd and" goal f-4: support research on women's health." phytoserm clinical trial also contributes to achieving the national alzheimer's disease project act (napa) to effectively prevent and treat ad by 2025 goal 1B. Phytoserm addresses a critical unmet need in women's health to reduce risk of alzheimer's in later life.

Transactions

Action Obligated Date
Amendment $1,353,297
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Original award $2,121,223
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Subawards

Subrecipient Amount Awarded
ADM Diagnostics, Inc. PhytoSERM Efficacy to Prevent Menopause Associated Decline in Brain Metabolism and Cognition: A Double-Blind, Randomized, Placebo-Controlled Phase 2 Clinical… $473,547
Weill Medical College Of Cornell University $2,067,168

Quick answers

Who received award R01AG075122?

R01AG075122 was awarded to University Of Arizona by National Institute on Aging (National Institutes of Health) on February 15, 2022.

How much is award R01AG075122 worth?

$18,872,590 has been obligated on R01AG075122.

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