Preserving the Metabolic Engine: Effects of HMB Supplementation on Skeletal Muscle Structure and Function During Semaglutide-Associated Weight Loss in Older Adults
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Change in Appendicular Lean Mass
研究概览
简要总结
This randomized, double-blind, placebo-controlled trial will evaluate whether daily calcium beta-hydroxy-beta-methylbutyrate (calcium-HMB) plus vitamin D3 preserves muscle mass, physical function, and resting metabolism in adults aged 65 to 85 years with type 2 diabetes who are newly starting semaglutide as part of usual clinical care. Participants will receive calcium-HMB plus vitamin D3 or matching placebo for approximately 6 months. The primary outcome is change in appendicular lean mass measured by dual-energy X-ray absorptiometry from baseline to month 6. Secondary assessments include body composition, muscle strength, physical performance, gait, physical activity, resting metabolic rate, metabolic measures, and whole-body quantitative computed tomography. An optional mechanistic substudy of up to 36 participants will include D3-creatine dilution, nonradioactive stable isotope infusions, repeated blood sampling, a standardized meal, breath sampling, and vastus lateralis muscle biopsies at baseline and month 6.
详细描述
Semaglutide treatment can produce substantial weight loss and improve glycemic control, but some weight loss may be accompanied by loss of lean tissue and skeletal muscle. Older adults with type 2 diabetes may be particularly vulnerable to loss of muscle mass, strength, mobility, and physical independence. Metabolic adaptation, defined as a reduction in resting metabolic rate beyond that expected from changes in body composition, may also occur during rapid weight loss.
Calcium-HMB is a leucine metabolite with anabolic and anti-catabolic properties. This study will test whether supplementation with calcium-HMB plus vitamin D3 during the first 6 months of standard-of-care semaglutide therapy preserves appendicular lean mass and improves physical and metabolic outcomes compared with placebo. Semaglutide is prescribed and managed by each participant's treating clinician and is not assigned, supplied, or managed by the research study.
Participants will be randomized 1:1, stratified by sex, to active study product or matching placebo. The active intervention provides 3 g calcium-HMB and 800 IU vitamin D3 daily. Main-study assessments occur at baseline, month 3, and month 6. Baseline and month 6 assessments include whole-body DXA, noncontrast whole-body quantitative CT, resting indirect calorimetry, blood and urine collection, strength and physical-function testing, gait assessment, questionnaires, and physical-activity assessment. Month 3 includes interval safety, adherence, medication, anthropometric, questionnaire, urine, and physical-function assessments as specified by the protocol.
Up to 36 participants, targeted as 18 per randomized group, may join optional Aim 3. Aim 3 includes D3-creatine dosing with timed urine collection, an overnight Clinical Research Center stay, two peripheral intravenous catheters, nonradioactive L-[ring-13C6]phenylalanine and Nτ-[2H3]-3-methylhistidine infusions, serial blood and breath sampling, a standardized meal, and three vastus lateralis muscle-biopsy time points during each baseline and month 6 metabolic visit. Aim 3 evaluates contractile muscle mass and muscle protein synthesis and breakdown. Blood collected in the main study also supports peripheral blood mononuclear cell isolation and ancillary immune analyses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
TSI/MTI or its designated independent code custodian maintains the treatment code. Active and placebo products are matched in appearance, packaging, labeling, and dosing schedule. Participants, the principal investigator, study coordinators, outcome assessors, and primary analysts remain blinded except for authorized personnel requiring access for product accountability or emergency safety unblinding.
入排标准
- 年龄范围
- 65 Years 至 85 Years（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 65 to 85 years, inclusive.
- •Type 2 diabetes mellitus, defined by HbA1c at or above 6.5% or current use of antihyperglycemic medication.
- •Body mass index at or above 27 kg/m
- •Newly initiating semaglutide as standard clinical care under the direction of a treating clinician.
- •Able to walk 400 meters without assistance; use of a cane is permitted.
- •Able to understand and provide legally effective informed consent.
- •English speaking for the initial study because the consent documents, questionnaires, study-product instructions, safety instructions, and procedure-specific materials are available only in English.
排除标准
- •Estimated glomerular filtration rate below 45 mL/min/1.73 m
- •Use of HMB, creatine, or high-dose whey protein supplements within the previous 3 months.
- •Weight change greater than 5% during the previous 3 months.
- •Recent fracture within the previous 6 months.
- •Neuromuscular disease, including Parkinson disease, or another condition that would interfere with study outcomes or safe participation.
- •Chronic corticosteroid use.
- •Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type
- •History of pancreatitis.
- •Smoking more than 7 cigarettes per day.
- •Previous malabsorptive or restrictive intestinal surgery or a malabsorptive syndrome.
- •Pregnancy or breastfeeding.
- •Recent history of neoplasia within the previous 5 years, as defined by the protocol.
- •Other active inflammatory conditions or neuromuscular disorders that could interfere with study outcomes or safety.
- •Serum 25-hydroxyvitamin D below 15 ng/mL.
- •Any medical, functional, laboratory, medication-related, or safety condition that the investigator determines makes study participation unsafe or prevents completion of essential procedures.
研究组 & 干预措施
Calcium-HMB Plus Vitamin D3
Participants receive active calcium-HMB plus vitamin D3 for approximately 6 months while semaglutide is prescribed and managed as standard clinical care.
干预措施: Calcium-HMB Plus Vitamin D3 (Dietary Supplement)
Matching Placebo
Participants receive matching placebo for approximately 6 months while semaglutide is prescribed and managed as standard clinical care.
干预措施: Matching placebo (Other)
结局指标
主要结局
Change in Appendicular Lean Mass
时间窗: Baseline to month 6
Appendicular lean mass will be measured by whole-body dual-energy X-ray absorptiometry. The outcome is the month-6 value minus the baseline value, reported in kilograms.
次要结局
- Title Change in Body Weight(Baseline to month 6)
- Change in Total Fat Mass(Baseline to month 6)
- Title Change in Visceral Adipose Tissue(Baseline to month 6)
- Change in Bone Mineral Density(Baseline to month 6)
- Change in Trabecular Bone Score(Baseline to month 6)
- Change in Glycated Hemoglobin(Time Frame Baseline to month 6)
- Change in Fasting Plasma Glucose(Baseline to month 6)
- Change in Resting Metabolic Rate(Baseline to month 6)
- Change in Handgrip Strength(Baseline, month 3, and month 6)
- Title Change in Lower-Extremity Strength or Torque(Baseline to month 6)
- Title Change in Short Physical Performance Battery Score(Baseline, month 3, and month 6)
- Change in Six-Minute Walk Distance(Baseline, month 3, and month 6)
- Change in Gait Measures(Baseline, month 3, and month 6)
- Change in Physical Activity(Protocol-defined monitoring periods at baseline or month 3 and month 6)
- Change in Whole-Body CT-Derived Muscle Volume and Composition(Baseline to month 6)
- Change in Total Body Creatine Pool Size(Baseline to month 6)
- Change in Myofibrillar Protein Synthesis(Baseline and month 6 Aim 3 metabolic visits)
- Change in Muscle Protein Breakdown(Baseline and month 6 Aim 3 metabolic visits)
- Change in Net Muscle Protein Balance(Baseline and month 6 Aim 3 metabolic visits)
- Change in Muscle Fiber Size and Type(Baseline to month 6)
- Study-Product Adherence(Through month 6)
- Incidence of Adverse Events(From first study-product dose through completion of month-6 follow-up or resolution/stabilization of ongoing events)
研究者
Charles R. Flynn
Associate Professor
Vanderbilt University Medical Center