Phase II RCT of High-dose Vitamin D Supplements in Older Adults without Dementia

大剂量维生素 D 补充剂治疗无痴呆症老年人的 II 期随机对照试验

• 批准号: 9904383
• 负责人: John M Olichney
• 金额: $ 93.17万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9904383
• 关键词: Abeta clearance; African American; Age; Alzheimer' s Disease; Alzheimer' s disease pathology; Amyloid beta-Protein; Antiinflammatory Effect; Antioxidants; Biological Markers; Blood; Brain; Brain region; Calcium; Caucasians; Cholecalciferol; Cognitive; Communities; Data; Dementia; Diagnostic; Diet; Dose; Effectiveness; Elderly; Enrollment; Episodic memory; Genetic Polymorphism; Genotype; Glutamates; High Prevalence; Hippocampus (Brain); Hispanics; Impaired cognition; Intake; Intervention; Latino; Low Prevalence; MRI Scans; Magnetic Resonance Imaging; Measures; Mediating; Metabolism; Neuropsychological Tests; Oral; Outcome; Oxidative Stress; Persons; Phase; Prevention; Public Health; Publishing; Randomized; Randomized Clinical Trials; Readability; Risk; Serum; Study of serum; Supplementation; Testing; Toxic effect; Urine; Vitamin D; Vitamin D Deficiency; Vitamin D supplementation; Vitamin D3 Receptor; White Matter Disease; aging brain; base; capsule; cerebral atrophy; cognitive change; cognitive function; cohort; compare effectiveness; dementia risk; design; ethnic diversity; executive function; improved; inflammatory marker; neuroimaging; neurotoxicity; novel; oral supplementation; phase 3 study; phase III trial; prevent; primary outcome; receptor; response; treatment effect; white matter

Project Summary/Abstract There is mounting evidence that low vitamin D blood levels are associated with increased risk of dementia and Alzheimer's disease (AD). There are several mechanisms by which low vitamin D status may promote AD pathology, including reduced β-amyloid (Aβ) clearance, dysregulation of calcium influx and glutamate- mediated neurotoxicity. Vitamin D interacts with receptors in the hippocampus and many other brain regions, and has established antioxidant and anti-inflammatory effects. Recent neuroimaging studies have found that low vitamin D levels are associated with increased periventricular white matter disease, reduced white matter volume and larger ventricles. Vitamin D deficiency may also have a toxic effect on brain function independent of Aβ metabolism. Preliminary studies of serum vitamin D levels in a diverse multi-ethnic cohort (n=382) of the UC Davis Alzheimer's Disease Center found a high prevalence of low vitamin D status (61% with levels <20 ng/ml), which was associated with faster rates of decline on executive function and episodic memory. This Phase II randomized clinical trial aims to test if supplementation with high dose oral vitamin D will successfully correct vitamin D insufficiency, compared to treatment with standard (RDA) dose vitamin D in a diverse community-based elderly cohort. The effect of high-dose vs. standard-dose vitamin D on altering cognitive trajectories will also be assessed and data will be expected to be used in designing a potential definitive Phase III trial in elderly groups at risk for dementia. A total of 180 elderly persons with longitudinal biomarkers, neuropsychological testing and brain MRI scans will be enrolled, with 152 (~50 with MCI, 50 with mild AD and 50 with no cognitive impairment) expected to complete the 3½-year study. One-half of each diagnostic group will be randomized to treatment with high-dose vitamin D3 (4,000 IU daily) or to standard dose Vitamin D (600 IU capsule daily + ~200 IU dietary = ~800 IU total/day). Longitudinal MRI analyses will provide an estimate of the treatment effect size on brain atrophy rate. Vitamin D receptor genotype polymorphisms and their impact on response to oral supplementation will also be examined. If vitamin D supplementation improves cognitive outcome, this could have a large impact on the public health, since low vitamin D status is a common, readably treatable condition which may provide a novel window to prevent dementia and AD. Furthermore, the higher prevalence of AD and dementia in African Americans and Latinos could be partially attributable to vitamin D insufficiency.

项目总结/文摘