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 目前推荐的随年龄增长而主要维持骨量的策略仅限于食用 富含维生素和矿物质的饮食以及进行负重活动。没有更具体、更有效的 随着年龄的增长，如何保持骨量，老年人会患骨质疏松症并增加骨折风险 需要处方药，且有副作用且费用有限。因此，安全需求尚未得到满足 对骨质流失的代谢过程进行有效的饮食干预。我们的长期目标是 开发安全有效的益生元/益生菌组合补充剂，用于饮食管理 骨质减少和骨质疏松症的代谢过程。该项目的目的是测试功效 在一项旨在提供骨骼的临床试验中益生菌/益生元组合（“合生元”） 对合生元作用的机制见解。我们的中心假设是一种新型的植物源医学 食品合生元（“SBD111”）将改善双能 X 射线吸收测定法 (DXA) 衍生的腰椎骨 矿物质密度 (BMD)、定量计算机断层扫描 (QCT) 衍生的骨强度 — 又名生物力学 计算机断层扫描分析 (BCT) 和体积骨密度 (vBMD)、骨转换标志物、 与安慰剂相比，老年女性（> 60 岁）的炎症和肠道微生物组功能。强者引导 初步数据 该假设将通过一项为期 18 个月的随机、双盲、安慰剂试验进行检验 对 220 名老年女性进行的对照临床试验。我们的具体目标是： 目标 1a 和 1b 确定 18 的效果 每日摄入 SBD111 的月数对腰椎 DXA-BMD 主要结果和次要结果的影响 （BCT 衍生的椎骨压缩骨强度、vBMD 和骨转换标志物）在女性中。目标 2a 和 2b 确定 18 个月每日摄入 SBD111 对炎症和肠道标志物的影响 女性微生物组的功能。我们将采用全宏基因组和宏转录组鸟枪测序 剖析肠道微生物组功能的变化[定义为糖基水解酶、甲萘醌 7 的变化，短 链脂肪酸（SCFA）和微生物多样性]，可以介导 SBD111 对骨转换和微生物多样性的影响 炎。我们还将考虑摄入总膳食纤维、益生元纤维和益生菌食品，这些食物可以 改变 SBD111 对骨骼、炎症和肠道微生物组的影响。 如果成功，这项拟议的试验将导致开发潜在安全、廉价的健康促进策略 用于骨质减少和骨质疏松症代谢过程的饮食管理。 1