Combination anti-amyloid therapy for preclinical Alzheimer's disease

临床前阿尔茨海默病的抗淀粉样蛋白联合治疗

• 批准号: 9786200
• 负责人: Paul S. Aisen
• 金额: $ 873.25万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9786200
• 关键词: Activities of Daily Living; Address; Alzheimer' s Disease; Alzheimer' s disease therapeutic; Alzheimer' s disease therapy; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-42; Amyloid beta-Protein; Antibodies; Atrophic; Award; Binding; Biological Markers; Biometry; Blood; Brain; Cerebrospinal Fluid; Clinic; Clinical; Clinical Trials; Clinical assessments; Cognition; Cognitive; Collaborations; Combined Modality Therapy; Committee Membership; Data; Development; Disease; Disease Progression; Enrollment; Epidemic; Futility; Generations; Hippocampus (Brain); Image; Impaired cognition; Individual; Intervention; Magnetic Resonance; Magnetic Resonance Imaging; Measures; Modification; Monitor; Neocortex; Nerve Degeneration; Neurobiology; Neurons; Oral; Participant; Pathologic; Pathology; Pathway interactions; Patient Self-Report; Pharmaceutical Preparations; Pharmacologic Substance; Placebos; Plasma; Positron-Emission Tomography; Prevention; Randomized; Randomized Controlled Trials; Regimen; Research Personnel; Safety; Sampling; Senile Plaques; Site; Symptoms; Testing; Therapeutic; Therapeutic Agents; Therapeutic Human Experimentation; Therapeutic Trials; Therapy trial; Treatment Protocols; Ventricular; Work; amyloid peptide; arm; asymptomatic Alzheimer' s disease; beta secretase; beta-site APP cleaving enzyme 1; clinical development; cognitive function; computerized; cooperative study; data management; design; drug development; effective therapy; efficacy evaluation; exosome; experience; high risk; improved; indexing; inhibitor/antagonist; instrument; neurofilament protein L; pre-clinical; pre-clinical therapy; prevent; primary outcome; secondary outcome; success; tau Proteins; tau-1; tool; uptake

PROJECT SUMMARY This is a multi-PI application for an R01 award under PAR-18-513. The proposed project titled “Combination Anti-Amyloid Therapy in Preclinical Alzheimer's Disease” is a multicenter randomized placebo-controlled two arm clinical trial of a combination anti-amyloid therapy: an anti-fibrillar amyloid antibody for the initial 18 months combined with BACE inhibition therapy for 4 years, in preclinical AD, defined as asymptomatic individuals with elevated brain amyloid as determined by florbetapir PET scanning. The primary outcome will be a cognitive composite (a modified version of the Preclinical Alzheimer's Cognitive Composite, PACC5), with functional and clinical assessments along with volumetric MR and tau PET as secondary outcomes (and, in a subset, CSF biomarkers). The specific Aims of the proposed study are; 1. to evaluate the impact of a combination anti-amyloid regimen on fibrillar amyloid in brain as indicated by amyloid PET SUVr, 2. to evaluate the efficacy and safety of a combination anti-amyloid regimen in individuals with preclinical AD, and 3. to evaluate the impact of the combination anti-amyloid regimen on AD biomarkers. Drs. Sperling and Aisen will share responsibility for scientific oversight of the clinical design and execution of the study and Imaging oversight will be provided by Dr. Johnson. The ACTC will provide the administrative and operational support, data capture and data management, clinical monitoring and site management, safety oversight, biostatistical support, and biomarker sample processing storage and support. Final selection of therapeutic agents for this trial will be made by a compound selection committee composed of field experts. Committee membership will include external experts in AD drug development and AD neurobiology, appointed in concert with NIA. The study team will work collaboratively with the pharmaceutical company researchers who have clinical experience with these therapeutics in development. This will be the first study of its kind: a potentially synergistic combination approach to dramatically reducing amyloid from asymptomatic individuals on the AD spectrum. Combination therapy trials are increasingly proposed by investigators and regulators to improve the likelihood of success in trials aiming for disease-modification. This approach could ultimately prevent the onset of AD symptoms

项目总结