The LUCINDA Trial

露辛达审判

• 批准号: 9988337
• 负责人: Craig S Atwood
• 金额: $ 141.31万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9988337
• 关键词: Acetylcholinesterase Inhibitors; Adult; Aftercare; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease patient; Alzheimer' s disease risk; Alzheimer' s disease therapy; Alzheimer’s disease biomarker; Amyloid deposition; Animal Model; Antiinflammatory Effect; Atrophic; Biological Markers; Brain region; C-reactive protein; Child; Clinical; Clinical Research; Cognition; Cognitive; Combined Modality Therapy; Data; Disease Progression; Dose; Double-Blind Method; Drug usage; Enantone; Erythrocyte Sedimentation Rate; FDA approved; Functional Magnetic Resonance Imaging; Goals; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone Analog; Hippocampus (Brain); IL6 gene; Impaired cognition; Inflammatory; Interleukin-1 beta; Legal patent; Leuprolide Acetate; Luteinizing Hormone; Magnetic Resonance Imaging; Malignant neoplasm of prostate; Measures; Motivation; Patients; Perfusion; Pharmaceutical Preparations; Pharmacologic Substance; Placebos; Plasma; Precocious Puberty; Process; Randomized Controlled Trials; Research Project Grants; Serum; Site; Spin Labels; Structure; Subgroup; TNF gene; Therapeutic; Time; United States National Institutes of Health; Uterine Fibroids; Validation; Ventricular; Woman; Work; base; clinical efficacy; cognitive performance; cost; cytokine; endometriosis; epidemiology study; functional decline; gray matter; improved; inflammatory marker; magnetic resonance imaging biomarker; neuroimaging; neuroimaging marker; novel; phase 2 study; phase II trial; phase III trial; pre-clinical; pre-clinical research; preservation; randomized trial; research and development; response; tau phosphorylation

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.

项目总结