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
Overview
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- Universidad de Burgos
- Enrollment
- 80
- Locations
- 1
- Primary Endpoint
- Short Physical Performance Battery (SPPB)
Overview
Brief Summary
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 80 adults aged ≥65 years will be 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.
Detailed Description
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 80 institutionalized adults aged ≥65 years will be recruited from nursing homes in the province of Burgos (Spain). Participants will be 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.
All participants will complete a supervised multicomponent exercise program conducted four times per week (~60 minutes per session). Exercise sessions will include resistance, balance, coordination, and flexibility training, with intensity individually adapted according to functional capacity using the Borg Rating of Perceived Exertion Scale.
Outcomes and Assessments
Clinical, functional, cognitive, and quality-of-life assessments will be conducted at baseline, post-intervention (Week 12), and during follow-up. Primary and secondary outcome measures focus on physical performance, muscle strength, body composition, cognitive function, activities of daily living, nutritional status, and quality of life.
Molecular and Biological Assessments
In addition to clinical outcomes, the study incorporates biological and molecular assessments to explore mechanistic pathways underlying functional adaptation and interindividual variability in response to supplementation and exercise. Venous blood samples will be collected for the analysis of inflammatory markers, oxidative stress and antioxidant status, hormonal profiles, and circulating and exosomal molecular signatures related to muscle metabolism and neuromuscular function. Body composition parameters will be assessed using dual-energy X-ray absorptiometry (DXA).
Statistical Analysis
Statistical analyses will be conducted using mixed-effects models appropriate for parallel-group randomized designs, with treatment group, time, and their interaction as fixed effects, and sex and age included as covariates where appropriate. Post-hoc pairwise comparisons will be adjusted for multiple testing. Statistical significance will be set at p < 0.05.
Ethics and Data Protection
The study was approved by the Ethics Committee of the University of Burgos (IR 24/2023). Written informed consent will be obtained from all participants or their legal representatives. All data will be pseudonymized and managed in accordance with the General Data Protection Regulation (GDPR) and Spanish data protection laws.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
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.
Eligibility Criteria
- Ages
- 65 Years to — (Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
Outcomes
Primary Outcomes
Short Physical Performance Battery (SPPB)
Time Frame: 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)
Time Frame: 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
Time Frame: 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.
Secondary Outcomes
- 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)
Investigators
Juan Francisco Mielgo
Full Professor of Physiology, Principal Investigator
Universidad de Burgos