Effects of Creatine Monohydrate and β-Hydroxy-β-Methylbutyrate Supplementation Combined With Multicomponent Exercise on Physical Performance, Cognition and Quality of Life in Institutionalized Older Adults: A Randomized Double-Blind Parallel-Group Trial
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Short Physical Performance Battery (SPPB)
研究概览
简要总结
Sarcopenia and physical frailty are highly prevalent among institutionalized older adults and are major contributors to functional decline, reduced mobility, and loss of independence. Combined exercise and targeted nutritional strategies have emerged as promising approaches to mitigate these age-related impairments.
This randomized, double-blind, placebo-controlled, parallel-group clinical trial aims to evaluate the independent and combined effects of creatine monohydrate (CRE) and β-hydroxy-β-methylbutyrate (HMB), administered alongside a supervised multicomponent exercise program, on physical function, body composition, cognitive performance, and quality of life in institutionalized older adults with physical frailty and sarcopenia.
A total of 50 adults aged ≥65 years were enrolled and randomized to one of four intervention groups for 12 weeks: placebo plus exercise, creatine plus exercise, HMB plus exercise, or creatine plus HMB plus exercise. A supplement-free follow-up period will be conducted to evaluate the sustainability of intervention effects.
In addition to clinical and functional outcomes, the study incorporates molecular and biological assessments to explore mechanistic pathways underlying functional adaptation and interindividual variability in response to the interventions.
详细描述
This randomized, double-blind, placebo-controlled, parallel-group clinical trial is designed to evaluate the independent and combined effects of creatine monohydrate (CRE) and β-hydroxy-β-methylbutyrate (HMB) supplementation when administered alongside a structured multicomponent exercise program in institutionalized older adults with physical frailty and sarcopenia. Sarcopenia and frailty are highly prevalent in this population and are associated with functional disability, increased health care utilization, and reduced quality of life. Nutritional strategies targeting muscle metabolism, when combined with systematic exercise, may attenuate functional decline and improve health outcomes in this vulnerable group.
Study Population and Design
A total of 50 institutionalized adults aged ≥65 years were enrolled from nursing homes in the province of Burgos (Spain). Participants were stratified by sex and randomized to one of four parallel intervention groups for a 12-week intervention period: placebo plus exercise, creatine plus exercise, HMB plus exercise, or creatine plus HMB plus exercise. All intervention groups will be followed by a supplement-free follow-up period to assess the persistence of intervention effects.
Intervention
Dietary supplementation will be administered once daily using identical sachets to ensure blinding and equivalent supplement volume across groups. Participants will receive a total of 6 g/day of powder, consisting of cellulose (placebo), creatine monohydrate, HMB, or their combinations, depending on group allocation. Supplement administration will be supervised by nursing staff and mixed with food or beverages according to standard procedures.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Triple-blind design: Participants, care providers (exercise supervisors and supplement distributors), investigators, and outcome assessors will remain blinded to allocation. Supplements will be provided in identical sachets.
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Institutionalized older adults (≥65 years) residing in the Fuentes Blancas Nursing Home (Diputación de Burgos).
- •Clinical diagnosis of frailty or sarcopenia according to validated criteria (e.g., Fried phenotype, SPPB ≤ 9, or low ALMI by DEXA).
- •Ability to participate in an exercise program as assessed by the medical staff.
- •Written informed consent provided by the participant or, if cognitively impaired, by a legally authorized representative.
排除标准
- •Severe renal insufficiency (eGFR < 30 mL/min/1.73m²) or liver failure.
- •Advanced heart failure (NYHA class III-IV) or unstable cardiovascular disease.
- •Active cancer or other severe medical conditions that contraindicate participation.
- •Severe cognitive impairment (MMSE < 10) precluding adherence to the program without caregiver support.
- •Known allergy or intolerance to creatine, HMB, or inulin.
- •Participation in another clinical trial within the past 3 months.
- •Any condition that, in the opinion of the medical team, may compromise safety or adherence to the intervention.
研究组 & 干预措施
Creatine + HMB + Exercise
Participants receive a total of 6 g/day of powder consisting of 3 g/day of creatine monohydrate and 3 g/day of β-hydroxy-β-methylbutyrate (HMB), administered once daily, combined with a supervised multicomponent exercise program for 12 weeks.
干预措施: Creatine Monohydrate (Dietary Supplement)
Creatine + HMB + Exercise
Participants receive a total of 6 g/day of powder consisting of 3 g/day of creatine monohydrate and 3 g/day of β-hydroxy-β-methylbutyrate (HMB), administered once daily, combined with a supervised multicomponent exercise program for 12 weeks.
干预措施: Multicomponent Exercise Program (Behavioral)
Creatine + HMB + Exercise
Participants receive a total of 6 g/day of powder consisting of 3 g/day of creatine monohydrate and 3 g/day of β-hydroxy-β-methylbutyrate (HMB), administered once daily, combined with a supervised multicomponent exercise program for 12 weeks.
干预措施: β-Hydroxy-β-Methylbutyrate (HMB) (Dietary Supplement)
Placebo + Exercise
Participants receive a total of 6 g/day of cellulose (placebo), administered once daily, combined with a supervised multicomponent exercise program for 12 weeks.
干预措施: Placebo (Cellulose) (Dietary Supplement)
Placebo + Exercise
Participants receive a total of 6 g/day of cellulose (placebo), administered once daily, combined with a supervised multicomponent exercise program for 12 weeks.
干预措施: Multicomponent Exercise Program (Behavioral)
Creatine + Exercise
Participants receive a total of 6 g/day of powder consisting of 3 g/day of creatine monohydrate and 3 g/day of cellulose (placebo filler), administered once daily, combined with a supervised multicomponent exercise program for 12 weeks.
干预措施: Placebo (Cellulose) (Dietary Supplement)
Creatine + Exercise
Participants receive a total of 6 g/day of powder consisting of 3 g/day of creatine monohydrate and 3 g/day of cellulose (placebo filler), administered once daily, combined with a supervised multicomponent exercise program for 12 weeks.
干预措施: Creatine Monohydrate (Dietary Supplement)
Creatine + Exercise
Participants receive a total of 6 g/day of powder consisting of 3 g/day of creatine monohydrate and 3 g/day of cellulose (placebo filler), administered once daily, combined with a supervised multicomponent exercise program for 12 weeks.
干预措施: Multicomponent Exercise Program (Behavioral)
HMB + Exercise
Participants receive a total of 6 g/day of powder consisting of 3 g/day of β-hydroxy-β-methylbutyrate (HMB) and 3 g/day of cellulose (placebo filler), administered once daily, combined with a supervised multicomponent exercise program for 12 weeks.
干预措施: Placebo (Cellulose) (Dietary Supplement)
HMB + Exercise
Participants receive a total of 6 g/day of powder consisting of 3 g/day of β-hydroxy-β-methylbutyrate (HMB) and 3 g/day of cellulose (placebo filler), administered once daily, combined with a supervised multicomponent exercise program for 12 weeks.
干预措施: Multicomponent Exercise Program (Behavioral)
HMB + Exercise
Participants receive a total of 6 g/day of powder consisting of 3 g/day of β-hydroxy-β-methylbutyrate (HMB) and 3 g/day of cellulose (placebo filler), administered once daily, combined with a supervised multicomponent exercise program for 12 weeks.
干预措施: β-Hydroxy-β-Methylbutyrate (HMB) (Dietary Supplement)
结局指标
主要结局
Short Physical Performance Battery (SPPB)
时间窗: Baseline, Week 12 (end of intervention), and 3-month follow-up
The SPPB assesses lower-extremity physical function through balance, gait speed, and chair stand components, generating a total score ranging from 0 to 12 (higher scores indicate better physical performance). Only the total score will be analyzed as the primary outcome.
Timed Up and Go (TUG)
时间窗: Baseline, Week 12 (end of intervention), and 3-month follow-up
Time in seconds to rise from a chair, walk 3 meters, turn around, return, and sit down. Lower times indicate better mobility and balance.
Appendicular Lean Mass (ALM, kg) by DEXA
时间窗: Baseline, Week 12 (end of intervention), and 3-month follow-up
Appendicular lean mass (sum of arms and legs lean tissue) measured in kilograms using DEXA. Higher values indicate greater muscle mass in limbs.
次要结局
- Incidence of Urinary or Fecal Incontinence(Baseline to 3-month follow-up)
- Total Antioxidant Capacity (TAC, mmol Trolox equivalents/L)(Baseline, Week 12 (end of intervention))
- Barthel Index(Baseline, Week 12 (end of intervention), and 3-month follow-up)
- Mini Nutritional Assessment (MNA)(Baseline, Week 12 (end of intervention), and 3-month follow-up)
- Cognitive Function - Mini-Mental State Examination (MMSE)(Baseline, Week 12 (end of intervention), and 3-month follow-up)
- Quality of Life - World Health Organization Quality of Life-Brief (WHOQOL-BREF)(Baseline, Week 12 (end of intervention), and 3-month follow-up)
- Total Lean Mass (kg) by DEXA(Baseline, Week 12 (end of intervention), and 3-month follow-up)
- Total Fat Mass (percent body weight) by DEXA(Baseline, Week 12 (end of intervention), and 3-month follow-up)
- Visceral Adipose Tissue (VAT, cm³) by DEXA(Baseline, Week 12 (end of intervention), and 3-month follow-up)
- Whole-Body Bone Mineral Density (BMD, g/cm²) by DEXA(Baseline, Week 12 (end of intervention), and 3-month follow-up)
- Cognitive Function - MEC (Spanish Adaptation of MMSE)(Baseline, Week 12 (end of intervention), and 3-month follow-up)
- Number of Falls(Baseline to 3-month follow-up)
- Number of Hospitalizations(Baseline to 3-month follow-up)
- Incidence of Respiratory and Urinary Infections(Baseline to 3-month follow-up)
- Incidence of Pressure Ulcers(Baseline to 3-month follow-up)
- Serum C-reactive protein (CRP, mg/L)(Baseline, Week 12 (end of intervention))
- Interleukin-6 (IL-6, pg/mL)(Baseline, Week 12 (end of intervention))
- Tumor Necrosis Factor-alpha (TNF-α, pg/mL)(Baseline, Week 12 (end of intervention))
- Reduced Glutathione (GSH, µmol/L)(Baseline, Week 12 (end of intervention))
- Oxidized Glutathione (GSSG, µmol/L)(Baseline, Week 12 (end of intervention))
- Grip Strength(Baseline, Week 12 (end of intervention), and 3-month follow-up)
- Leg and Back Isometric Strength(Baseline, Week 12 (end of intervention), and 3-month follow-up)
- Seated Arm Curl Test(Baseline, Week 12 (end of intervention), and 3-month follow-up)
- Thiobarbituric Acid Reactive Substances (TBARS, nmol MDA equivalents/mL plasma)(Baseline, Week 12 (end of intervention))
- Malondialdehyde (MDA, µmol/L)(Baseline, Week 12 (end of intervention))
- Grip Strength(Baseline, Week 12 (end of intervention), and 3-month follow-up)
- Leg and Back Isometric Strength(Baseline, Week 12 (end of intervention), and 3-month follow-up)
- Seated Arm Curl Test(Baseline, Week 12 (end of intervention), and 3-month follow-up)
- Barthel Index(Baseline, Week 12 (end of intervention), and 3-month follow-up)
- Total Fat Mass (percent body weight) by DEXA(Baseline, Week 12 (end of intervention), and 3-month follow-up)
- Mini Nutritional Assessment (MNA)(Baseline, Week 12 (end of intervention), and 3-month follow-up)
- Cognitive Function - Mini-Mental State Examination (MMSE)(Baseline, Week 12 (end of intervention), and 3-month follow-up)
- Quality of Life - World Health Organization Quality of Life-Brief (WHOQOL-BREF)(Baseline, Week 12 (end of intervention), and 3-month follow-up)
- Total Lean Mass (kg) by DEXA(Baseline, Week 12 (end of intervention), and 3-month follow-up)
- Visceral Adipose Tissue (VAT, cm³) by DEXA(Baseline, Week 12 (end of intervention), and 3-month follow-up)
- Whole-Body Bone Mineral Density (BMD, g/cm²) by DEXA(Baseline, Week 12 (end of intervention), and 3-month follow-up)
- Cognitive Function - MEC (Spanish Adaptation of MMSE)(Baseline, Week 12 (end of intervention), and 3-month follow-up)
- Number of Falls(Baseline to 3-month follow-up)
- Number of Hospitalizations(Baseline to 3-month follow-up)
- Incidence of Respiratory and Urinary Infections(Baseline to 3-month follow-up)
- Incidence of Pressure Ulcers(Baseline to 3-month follow-up)
- Incidence of Urinary or Fecal Incontinence(Baseline to 3-month follow-up)
- Serum C-reactive protein (CRP, mg/L)(Baseline, Week 12 (end of intervention))
- Interleukin-6 (IL-6, pg/mL)(Baseline, Week 12 (end of intervention))
- Tumor Necrosis Factor-alpha (TNF-α, pg/mL)(Baseline, Week 12 (end of intervention))
- Reduced Glutathione (GSH, µmol/L)(Baseline, Week 12 (end of intervention))
- Oxidized Glutathione (GSSG, µmol/L)(Baseline, Week 12 (end of intervention))
- Thiobarbituric Acid Reactive Substances (TBARS, nmol MDA equivalents/mL plasma)(Baseline, Week 12 (end of intervention))
- Malondialdehyde (MDA, µmol/L)(Baseline, Week 12 (end of intervention))
- Total Antioxidant Capacity (TAC, mmol Trolox equivalents/L)(Baseline, Week 12 (end of intervention))
- Relative expression levels of selected circulating microRNAs(Baseline, Week 12 (end of intervention), and 3-month follow-up)
- Relative expression levels of selected exosome-derived microRNAs(Baseline and Week 12)
- Frequency of selected genetic variants related to creatine and HMB responsiveness(Baseline)
- Relative abundance of selected circulating proteins involved in muscle and inflammatory responses(Baseline and Week 12)
研究者
Juan Francisco Mielgo
Full Professor of Physiology, Principal Investigator
Universidad de Burgos