PhytoSERM for Menopausal Hot Flashes and Sustained Brain Health

PhytoSERM 针对更年期潮热和持续大脑健康

• 批准号: 10707107
• 负责人: ROBERTA EILEEN BRINTON
• 金额: $ 119.93万
• 依托单位: NEUTHERAPEUTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10707107
• 关键词: 3 year old; Address; Age; Age Years; Aging; Alternative Health; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Alzheimer’s disease biomarker; American; Assessment tool; Biological Markers; Blood; Body Composition; Bone Density; Brain; Breast; Breast Cancer Risk Factor; Cell Proliferation; Clinical; Clinical Research; Clinical Trials; Cognition; Development; Disease; Double-Blind Method; Drug Kinetics; Elderly; Endocrine; Estrogen Receptor beta; Estrogen Therapy; Estrogens; Exhibits; Female; Formulation; Frequencies; Fright; Galvanic Skin Response; Genistein; Goals; Health; Hormones; Hot flushes; Inflammatory; Intervention; Life; Mammary Gland Parenchyma; Measures; Medical; Menopausal Symptom; Menopause; Menstruation; Metabolic; Monitor; National Institute on Aging; Neurologic; Neurosecretory Systems; Night Sweating; Participant; Perimenopause; Personal Satisfaction; Phase; Phenotype; Physiological; Phytoestrogens; Placebos; Plants; Postmenopause; Prevention strategy; Proliferating; Randomized; Research Support; Risk; Risk Reduction; Selective Estrogen Receptor Modulators; Severities; Sleep; Sleep disturbances; Symptoms; Technology; Therapeutic; Time; Tissues; Translating; Translations; Uterus; Woman; Women' s Health; Wrist; age related; aged; associated symptom; blood-based biomarker; brain health; clinical development; cognitive function; critical period; daidzein; data acquisition; digital; effective intervention; effective therapy; efficacy evaluation; equol; estrogenic; experience; hormone therapy; innovation; lifetime risk; lipidomics; malignant breast neoplasm; menopausal aging; menopausal hormone therapy; middle age; open label; oral supplementation; placebo group; pre-clinical; prevent; randomized placebo-controlled clinical trial; rational design; reproductive; treatment strategy; wearable device; 3 year old; Address; Age; Age Years; Aging; Alternative Health; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Alzheimer’s disease biomarker; American; Assessment tool; Biological Markers; Blood; Body Composition; Bone Density; Brain; Breast; Breast Cancer Risk Factor; Cell Proliferation; Clinical; Clinical Research; Clinical Trials; Cognition; Development; Disease; Double-Blind Method; Drug Kinetics; Elderly; Endocrine; Estrogen Receptor beta; Estrogen Therapy; Estrogens; Exhibits; Female; Formulation; Frequencies; Fright; Galvanic Skin Response; Genistein; Goals; Health; Hormones; Hot flushes; Inflammatory; Intervention; Life; Mammary Gland Parenchyma; Measures; Medical; Menopausal Symptom; Menopause; Menstruation; Metabolic; Monitor; National Institute on Aging; Neurologic; Neurosecretory Systems; Night Sweating; Participant; Perimenopause; Personal Satisfaction; Phase; Phenotype; Physiological; Phytoestrogens; Placebos; Plants; Postmenopause; Prevention strategy; Proliferating; Randomized; Research Support; Risk; Risk Reduction; Selective Estrogen Receptor Modulators; Severities; Sleep; Sleep disturbances; Symptoms; Technology; Therapeutic; Time; Tissues; Translating; Translations; Uterus; Woman; Women' s Health; Wrist; age related; aged; associated symptom; blood-based biomarker; brain health; clinical development; cognitive function; critical period; daidzein; data acquisition; digital; effective intervention; effective therapy; efficacy evaluation; equol; estrogenic; experience; hormone therapy; innovation; lifetime risk; lipidomics; malignant breast neoplasm; menopausal aging; menopausal hormone therapy; middle age; open label; oral supplementation; placebo group; pre-clinical; prevent; randomized placebo-controlled clinical trial; rational design; reproductive; treatment strategy; wearable device

PROJECT SUMMARY/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, parallel-group, randomized, placebo-controlled clinical trial with an open-label extension to determine efficacy of PhytoSERM in symptomatic peri- and post-menopausal women. Primary objectives are to determine the efficacy of PhytoSERM to alleviate menopausal symptoms, mainly hot flashes. Secondary objectives are to evaluate the effect of PhytoSERM on: 1) cognitive function, 2) sleep disturbances, and 3) non-neurologic menopausal symptoms, including bone mineral density and body composition. Tertiary objectives are to determine impact of PhytoSERM on blood-based AD biomarkers. This 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.

项目摘要/摘要 妇女患阿尔茨海默氏病（AD）的终身风险更大。当多个AD风险状况可能出现并且与该疾病的前驱 /临床前特征一致时，导致AD生命更大的可能性的潜在因素是中年间内分泌老化过渡的中期。虽然在绝经女性有症状时进行的雌激素或马酮治疗可以降低AD的风险，但对乳腺癌的恐惧会导致许多女性放弃这种方法。雌激素疗法的一种创新替代方法是靶向大脑中的雌激素作用，同时避免乳腺组织中与雌激素相关的增殖。为了实现这一目标，我们提出了“植物类剂”的临床发展，这是一种选择性的雌激素受体β（ERß）调节剂，该调节剂在生殖组织中抑制脑中通过ERß促进雌激素作用。 Phytoserm是一种由3个植物雌激素的合理设计的公式（通常每种植物雌激素被FDA确定为安全）。我们较早的NIA支持Phytoserm阶段1B/2A临床试验，确定植物度是安全且耐受性良好，暴露的预测性药代动力学在骨膜和术后妇女中，并鉴定出响应剂表型（https://clinicalicals.gov/clinicals.gov/ct2/ct2/ct2/show/show/nct011723392339117）本文提出的是第2阶段，双盲，平行组，随机，安慰剂对照的临床试验，并进行开放标签扩展，以确定植物血管在症状症状周期和绝经后妇女中的有效性。主要目标是确定植物血剂可减轻更年期症状的有效性，主要是潮热。次要目标是评估植物剂对：1）认知功能，2）睡眠障碍和3）非神经绝经症状，包括骨矿物质密度和身体成分。三级目标旨在确定植物酶对基于血液的AD生物标志物的影响。该第2阶段的植物血临床试验介绍了美国国家机构在衰老2020-2025的多个战略方向：在21世纪涉及的衰老良好，特别是目标C-3，“开发有效的干预措施，以维持健康，幸福感，功能，功能，防止或减少与年龄相关的疾病的燃烧”，并进行新的临床研究 /临床临床临时性的临床划分，” 设置。“目标D-4：将基本发现转化为AD/ADRD的有效治疗和/或预防策略，“目标F-4：支持妇女健康研究的研究”。 Phytoserm临床试验还有助于实现《国家阿尔茨海默氏病项目法》（NAPA），以在2025年目标1B之前有效预防和治疗AD。