A randomized, double-blind, placebo-controlled, clinical trial of a probiotic/prebiotic supplement for the dietary management of age-related bone loss.

益生菌/益生元补充剂用于饮食管理与年龄相关的骨质流失的随机、双盲、安慰剂对照临床试验。

• 批准号: 10733549
• 负责人: Shivani Sahni
• 金额: $ 61.15万
• 依托单位: HEBREW REHABILITATION CENTER FOR AGED
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10733549
• 关键词: Adult; Age; Age-Related Bone Loss; Aging; American; Biochemical Markers; Biomechanics; Bone Density; Clinical; Clinical Research; Clinical Trials; Colon; Compressive Strength; Consumption; Controlled Clinical Trials; Data; Development; Diet; Dietary Fiber; Dietary Intervention; Double-Blind Method; Drug Prescriptions; Dual-Energy X-Ray Absorptiometry; Elderly; Enzymes; Equilibrium; Feces; Fermentation; Fiber; Food; Food Supplements; Fracture; Genes; Goals; Guidelines; Health Promotion; Homologous Gene; Hydrolase; Inflammation; Intake; Interleukins; Maintenance; Measures; Mediating; Metabolism; Microbe; Minerals; Mus; Osteitis; Osteopenia; Osteoporosis; Pathway interactions; Peripheral; Placebo Control; Placebos; Plants; Postmenopause; Probiotics; Production; Public Health; Randomized; Recommendation; Regulatory T-Lymphocyte; Shotgun Sequencing; Skeleton; TNF gene; Testing; Vertebral column; Vitamin K 2; Vitamins; Volatile Fatty Acids; Weight-Bearing state; Woman; X-Ray Computed Tomography; aged; bone; bone loss; bone mass; bone strength; bone turnover; comparison control; cost; design; dietary; efficacy testing; fracture risk; fruits and vegetables; gut microbes; gut microbiome; improved; inflammatory marker; insight; medical food; metagenome; metatranscriptome; microbial; middle age; mouse model; novel; older women; osteoclastogenesis; prebiotics; preclinical study; primary outcome; secondary outcome; side effect; skeletal; spine bone structure

ABSTRACT / PROJECT SUMMARY Currently recommended strategies for primary maintenance of bone mass with age are limited to consuming a diet rich in vitamins and minerals and performing weight bearing activity. Without more specific and effective ways to maintain bone mass with age, older adults will develop osteoporosis and elevated fracture risk necessitating prescription drugs, with side effects and restrictive costs. Hence, there is an unmet need for safe and effective dietary interventions for the metabolic processes underlying bone loss. Our long term goal is to develop safe and effective prebiotic/probiotic combination supplements for the dietary management of the metabolic processes underlying osteopenia and osteoporosis. The objective of this project is to test the efficacy of an probiotic/prebiotic combination (“synbiotic”) on the skeleton in a clinical trial that is designed to provide mechanistic insights into the action of the synbiotic. Our central hypothesis is that a novel plant-derived medical food synbiotic (“SBD111”) will improve dual energy x-ray absorptiometry (DXA) derived lumbar spine bone mineral density (BMD), quantitative computed tomography (QCT) derived bone strength — aka Biomechanical Computed Tomography analysis, or BCT— and volumetric BMD (vBMD), markers of bone turnover, inflammation, and gut microbiome function in older women (>60 years) compared to placebo. Guided by strong preliminary data this hypothesis will be tested by performing an 18-month randomized, double-blinded, placebo- controlled clinical trial in 220 older women. Our specific aims are: Aim 1a and 1b To determine the effect of 18 months of daily intake of SBD111 on the primary outcome of lumbar spine DXA-BMD and secondary outcomes (BCT-derived vertebral compressive bone strength, vBMD, and markers of bone turnover) in women. Aim 2a and 2b To determine the effect of 18 months of daily intake of SBD111 on markers of inflammation and gut microbiome function in women. We will employ whole metagenome and meta-transcriptome shotgun sequencing to dissect changes in gut microbiome function [defined as changes in glycosyl hydrolase, menaquinone 7, short chain fatty acid (SCFA), and microbial diversity], which can mediate the effect of SBD111 on bone turnover and inflammation. We will also consider intake of total dietary fiber, prebiotic fiber, and probiotic foods that could modify the effect of SBD111 on bone, inflammation, and gut microbiome. If successful, this proposed trial will lead to developing potentially safe, inexpensive health promoting strategies for the dietary management of the metabolic processes underlying osteopenia and osteoporosis. 1

摘要 /项目摘要 目前，建议的骨骼质量初步维持随着年龄的年龄的推荐策略仅限于消费 饮食富含维生素和矿物质，并进行体重轴承活性。 随着年龄的增长，老年人将骨质疏松症和骨折风险升高的方法保持骨质。 需要处方药，具有副作用和限制性成本。 对于代谢过程的有效饮食介入，我们的长期目标是 为饮食管理开发安全有效的益生元/益生菌组合补充剂 骨质减少症和骨质疏松症的代谢过程。 在临床试验中骨骼上的益生菌/益生元组合（“合成生”）的 我们中心假设的机械洞察力是一种新型的植物衍生的医学 食物合成剂（“ SBD111”）将改善双能X射线吸收法（DXA）衍生的腰椎骨骨骨 矿物密度（BMD），定量计算机断层扫描（QCT）衍生的骨强度 - 又名生物力学 计算的示意图分析或BCT和体积BMD（VBMD），骨转换标记， 与安慰剂相比，老年女性的炎症和肠道微生物组功能 初步数据该假设将通过执行18个月的随机，双盲，安慰剂 - 220名妇女的受控临床试验是：确定18的效果 SBD111每天摄入腰椎DXA-BMD和次级结果的主要结果 （BCT衍生的椎骨强度，VBMD和骨转换标记）在AIM 2A中 和2b确定SBD111每天摄入18个月对炎症和肠道标记的影响 女性的微生物组功能。 剖析肠道微生物组功能的变化 链脂肪酸（SCFA）和微生物多样性，可以介导SBD111对骨转换和 炎症。 修改SBD111对骨骼，炎症和肠道微生物组的影响。 如果成功，该支撑审判将导致制定高昂的安全，廉价的健康促进策略 为了对代谢过程的饮食管理Seeopenia和骨质疏松症。 1