FrailtyMULTI-FRAILNCT07275996
Neuromuscular and Multi-Omics Synergy of Combined Creatine × HMB Supplementation Plus Exercise to Improve Muscle Function in Sarcopenic Frailty
A study testing Creatine Monohydrate, Multicomponent Exercise Program and β-Hydroxy-β-Methylbutyrate (HMB) in people with Frailty and Sarcopenia, run by Universidad de Burgos at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Frailty, Sarcopenia, Aging
- What is being tested?
- Creatine Monohydrate, Multicomponent Exercise Program and β-Hydroxy-β-Methylbutyrate (HMB)
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteSpain
- Study dates
- 10 Mar 2026to 30 May 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Spain1 site
Residencia de Mayores Fuentes Blancas (Diputación Provincial de Burgos)
Burgos, Castille and León, 09002
About this study
Official title: 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
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.
Read more
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.
Read the 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 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.
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 was 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.
- Conditions
- Frailty, Sarcopenia, Aging, Malnutrition Elderly
- Being tested
- Placebo (Cellulose), Creatine Monohydrate, Multicomponent Exercise Program, β-Hydroxy-β-Methylbutyrate (HMB)
- Keywords
- creatine, HMB, supplementation, multicomponent exercise, concurrent training, institutionalized older adults, nursing home, physical performance, quality of life, oxidative stress, inflammation, geriatric assessment, multi-omics, microRNA, proteomics
- Medical subject headings
- Frailty, Sarcopenia, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo (Cellulose)Dietary supplement
Sachets containing cellulose used as placebo filler to match supplement volume, appearance, and taste. Administered once daily, mixed with yogurt or juice, during the intervention period.
Creatine MonohydrateDietary supplement
Sachets containing creatine monohydrate used as an active dietary supplement. Administered once daily during the intervention period.
Multicomponent Exercise ProgramBehavioural
Supervised exercise sessions, 4 times per week (~60 minutes each), including resistance, endurance, balance, coordination, and flexibility training. Intensity adapted to participants' functional status (Borg scale 6-9). Conducted throughout the 12-week intervention period.
β-Hydroxy-β-Methylbutyrate (HMB)Dietary supplement
Sachets containing calcium β-hydroxy-β-methylbutyrate used as an active dietary supplement. Administered once daily during the intervention period.
| Study group | Role | What they receive |
|---|---|---|
| Creatine + HMB + Exercise | Experimental | 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. Receives: Dietary Supplement: Creatine Monohydrate; Behavioral: Multicomponent Exercise Program; Dietary Supplement: β-Hydroxy-β-Methylbutyrate (HMB) |
| Placebo + Exercise | Placebo comparator | Participants receive a total of 6 g/day of cellulose (placebo), administered once daily, combined with a supervised multicomponent exercise program for 12 weeks. Receives: Dietary Supplement: Placebo (Cellulose); Behavioral: Multicomponent Exercise Program |
| Creatine + Exercise | Active comparator | 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. Receives: Dietary Supplement: Placebo (Cellulose); Dietary Supplement: Creatine Monohydrate; Behavioral: Multicomponent Exercise Program |
| HMB + Exercise | Active comparator | 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. Receives: Dietary Supplement: Placebo (Cellulose); Behavioral: Multicomponent Exercise Program; Dietary Supplement: β-Hydroxy-β-Methylbutyrate (HMB) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Short Physical Performance Battery (SPPB)
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.
Measured: Baseline, Week 12 (end of intervention), and 3-month follow-up
Timed Up and Go (TUG)
Time in seconds to rise from a chair, walk 3 meters, turn around, return, and sit down. Lower times indicate better mobility and balance.
Measured: Baseline, Week 12 (end of intervention), and 3-month follow-up
Appendicular Lean Mass (ALM, kg) by DEXA
Appendicular lean mass (sum of arms and legs lean tissue) measured in kilograms using DEXA. Higher values indicate greater muscle mass in limbs.
Measured: Baseline, Week 12 (end of intervention), and 3-month follow-up
Secondary outcomes (29)
Grip Strength
Maximal isometric handgrip strength measured in kilograms using a validated hydraulic dynamometer (e.g., Jamar Plus+). Each test performed with the dominant hand in seated position, elbow at 90°. Best of three attempts recorded.
Measured: Baseline, Week 12 (end of intervention), and 3-month follow-up
Leg and Back Isometric Strength
Maximal isometric strength of leg and back extensors assessed in kilograms using a back/leg dynamometer (e.g., Baseline Evaluation Dynamometer). Participants stand on the platform and pull a fixed bar upwards. Best of two attempts recorded.
Measured: Baseline, Week 12 (end of intervention), and 3-month follow-up
Seated Arm Curl Test
Dynamic strength/endurance of upper limbs measured as the number of full arm curl repetitions in 30 seconds using a 2 kg dumbbell for women and a 4 kg dumbbell for men. Participants are seated upright without armrests.
Measured: Baseline, Week 12 (end of intervention), and 3-month follow-up
Barthel Index
Measure of independence in activities of daily living (feeding, bathing, mobility, toileting, etc.). Score ranges from 0 (total dependence) to 100 (independent).
Measured: Baseline, Week 12 (end of intervention), and 3-month follow-up
Mini Nutritional Assessment (MNA)
Validated tool to screen and assess nutritional status in older adults. Score ranges from 0-30 (higher = better nutritional status).
Measured: Baseline, Week 12 (end of intervention), and 3-month follow-up
Cognitive Function - Mini-Mental State Examination (MMSE)
Cognitive function assessed using the Mini-Mental State Examination (MMSE). Scores range from 0 to 30, with higher scores indicating better cognition.
Measured: Baseline, Week 12 (end of intervention), and 3-month follow-up
Quality of Life - World Health Organization Quality of Life-Brief (WHOQOL-BREF)
26-item validated questionnaire covering physical, psychological, social and environmental domains.
Scores range from 26 to 130; higher scores indicate better perceived quality of life.
Measured: Baseline, Week 12 (end of intervention), and 3-month follow-up
Total Lean Mass (kg) by DEXA
Whole-body lean soft tissue mass measured in kilograms using DEXA (Hologic Discovery or GE Lunar system) with manufacturer's software and standardized positioning. Higher values indicate greater muscle mass.
Measured: Baseline, Week 12 (end of intervention), and 3-month follow-up
Total Fat Mass (percent body weight) by DEXA
Whole-body fat mass measured with DEXA and expressed as a percentage of total body weight. Higher values indicate greater adiposity.
Measured: Baseline, Week 12 (end of intervention), and 3-month follow-up
Visceral Adipose Tissue (VAT, cm³) by DEXA
Visceral adipose tissue (VAT) volume estimated by DEXA in the android region of interest, expressed in cubic centimeters (cm³). Higher values indicate greater central adiposity.
Measured: Baseline, Week 12 (end of intervention), and 3-month follow-up
Whole-Body Bone Mineral Density (BMD, g/cm²) by DEXA
Whole-body BMD measured by DEXA, expressed as grams per square centimeter (g/cm²). Higher values indicate greater bone mineral density.
Measured: Baseline, Week 12 (end of intervention), and 3-month follow-up
Cognitive Function - MEC (Spanish Adaptation of MMSE)
Cognitive function assessed using the MEC (Spanish version of the MMSE). Scores range from 0 to 35, with higher scores indicating better cognition.
Measured: Baseline, Week 12 (end of intervention), and 3-month follow-up
Number of Falls
Incidence of falls recorded by nursing staff during the study period. Unit: number of events per participant. Lower numbers indicate better outcomes.
Measured: Baseline to 3-month follow-up
Number of Hospitalizations
Incidence of hospital admissions for any cause. Unit: number of events per participant. Lower numbers indicate better outcomes.
Measured: Baseline to 3-month follow-up
Incidence of Respiratory and Urinary Infections
Number of documented respiratory and/or urinary tract infections. Unit: number of events per participant. Lower numbers indicate better outcomes.
Measured: Baseline to 3-month follow-up
Incidence of Pressure Ulcers
Number of new pressure ulcers recorded by nursing staff. Lower numbers indicate better outcomes.
Measured: Baseline to 3-month follow-up
Incidence of Urinary or Fecal Incontinence
Occurrence of urinary and/or fecal incontinence episodes recorded in clinical charts. Lower numbers indicate better outcomes.
Measured: Baseline to 3-month follow-up
Serum C-reactive protein (CRP, mg/L)
CRP will be measured in serum samples using a high-sensitivity ELISA. Results expressed in mg/L. Higher values indicate greater systemic inflammation.
Measured: Baseline, Week 12 (end of intervention)
Interleukin-6 (IL-6, pg/mL)
Serum IL-6 concentration will be measured by ELISA and expressed in pg/mL. Higher values indicate greater systemic inflammation.
Measured: Baseline, Week 12 (end of intervention)
Tumor Necrosis Factor-alpha (TNF-α, pg/mL)
Serum TNF-α concentration will be determined by ELISA and expressed in pg/mL. Higher values indicate greater systemic inflammation.
Measured: Baseline, Week 12 (end of intervention)
Reduced Glutathione (GSH, µmol/L)
Plasma reduced glutathione measured by colorimetric assay and expressed in µmol/L. Higher values indicate better antioxidant status.
Measured: Baseline, Week 12 (end of intervention)
Oxidized Glutathione (GSSG, µmol/L)
Plasma oxidized glutathione measured by colorimetric assay and expressed in µmol/L. Higher values indicate greater oxidative stress.
Measured: Baseline, Week 12 (end of intervention)
Thiobarbituric Acid Reactive Substances (TBARS, nmol MDA equivalents/mL plasma)
Lipid peroxidation index measured as TBARS and expressed in nmol MDA equivalents/mL of plasma. Higher values indicate greater oxidative stress.
Measured: Baseline, Week 12 (end of intervention)
Malondialdehyde (MDA, µmol/L)
Plasma MDA determined spectrophotometrically and expressed in µmol/L. Higher values indicate greater oxidative stress.
Measured: Baseline, Week 12 (end of intervention)
Total Antioxidant Capacity (TAC, mmol Trolox equivalents/L)
Plasma TAC measured using colorimetric assay and expressed as mmol Trolox equivalents/L. Higher values indicate better antioxidant defense.
Measured: Baseline, Week 12 (end of intervention)
Relative expression levels of selected circulating microRNAs
Changes in the relative expression levels of selected circulating microRNAs associated with muscle metabolism, neuromuscular function, inflammation, oxidative stress, and anabolic signaling pathways. MicroRNAs will be quantified from peripheral blood samples using molecular profiling techniques.
Measured: Baseline, Week 12 (end of intervention), and 3-month follow-up
Relative expression levels of selected exosome-derived microRNAs
Changes in the relative expression levels of selected exosome-derived microRNAs related to muscle function, inflammation, and metabolic regulation, analyzed from circulating extracellular vesicles isolated from plasma samples.
Measured: Baseline and Week 12
Frequency of selected genetic variants related to creatine and HMB responsiveness
Analysis of the frequency of selected genetic variants related to muscle metabolism, anabolic signaling, and exercise responsiveness to explore interindividual variability in functional and molecular responses to creatine and HMB supplementation.
Measured: Baseline
Relative abundance of selected circulating proteins involved in muscle and inflammatory responses
Changes in the relative abundance of selected circulating proteins involved in muscle metabolism, inflammation, oxidative stress, and functional adaptation in response to creatine and HMB supplementation combined with exercise. Protein abundance will be assessed using targeted proteomic approaches.
Measured: Baseline and Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2025
- Study start10 Mar 2026
- Primary completion30 Dec 2026 (estimated)
- Study completion30 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for FrailtyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, double-blind, placebo-controlled, parallel-group clinical trial with four study arms. Participants will receive 12 weeks of dietary supplementation combined with a supervised multicomponent exercise program, followed by a 3-month follow-up period without supplementation.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universidad de Burgos
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Juan Francisco Mielgo, Universidad de Burgos
- Investigators
- Juan Mielgo-Ayuso, PhD, Study chair, Universidad de Burgos
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07275996
- Sponsor's protocol ID
- UBU-FB-CREHMB-CRXO-2025
- Other IDs
- IR 24/2023
- Acronym
- MULTI-FRAIL
- Status last verified
- Apr 2026
- First submitted
- 29 Sep 2025
- Last updated
- 4 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) underlying the published results of this trial (including baseline characteristics and outcome measures) will be made available to qualified researchers upon reasonable request. Data will be shared only after publication of the main results and following approval of a research proposal and data access agreement.
Publications
Rezola-Pardo C, Rodriguez-Larrad A, Gomez-Diaz J, Lozano-Real G, Mugica-Errazquin I, Patino MJ, Bidaurrazaga-Letona I, Irazusta J, Gil SM. Comparison Between Multicomponent Exercise and Walking Interventions in Long-Term Nursing Homes: A Randomized Controlled Trial. Gerontologist. 2020 Sep 15;60(7):1364-1373. doi: 10.1093/geront/gnz177.
PubMed 31845733Fernandez-Landa J, Calleja-Gonzalez J, Leon-Guereno P, Caballero-Garcia A, Cordova A, Mielgo-Ayuso J. Effect of the Combination of Creatine Monohydrate Plus HMB Supplementation on Sports Performance, Body Composition, Markers of Muscle Damage and Hormone Status: A Systematic Review. Nutrients. 2019 Oct 20;11(10):2528. doi: 10.3390/nu11102528.
PubMed 31635165Fernandez-Landa J, Fernandez-Lazaro D, Calleja-Gonzalez J, Caballero-Garcia A, Cordova A, Leon-Guereno P, Mielgo-Ayuso J. Long-Term Effect of Combination of Creatine Monohydrate Plus beta-Hydroxy beta-Methylbutyrate (HMB) on Exercise-Induced Muscle Damage and Anabolic/Catabolic Hormones in Elite Male Endurance Athletes. Biomolecules. 2020 Jan 15;10(1):140. doi: 10.3390/biom10010140.
PubMed 31952174Fernandez-Landa J, Fernandez-Lazaro D, Calleja-Gonzalez J, Caballero-Garcia A, Cordova Martinez A, Leon-Guereno P, Mielgo-Ayuso J. Effect of Ten Weeks of Creatine Monohydrate Plus HMB Supplementation on Athletic Performance Tests in Elite Male Endurance Athletes. Nutrients. 2020 Jan 10;12(1):193. doi: 10.3390/nu12010193.
PubMed 31936727Holecek M. Beta-hydroxy-beta-methylbutyrate supplementation and skeletal muscle in healthy and muscle-wasting conditions. J Cachexia Sarcopenia Muscle. 2017 Aug;8(4):529-541. doi: 10.1002/jcsm.12208. Epub 2017 May 10.
PubMed 28493406Cadore EL, Rodriguez-Manas L, Sinclair A, Izquierdo M. Effects of different exercise interventions on risk of falls, gait ability, and balance in physically frail older adults: a systematic review. Rejuvenation Res. 2013 Apr;16(2):105-14. doi: 10.1089/rej.2012.1397.
PubMed 23327448Devries MC, Phillips SM. Creatine supplementation during resistance training in older adults-a meta-analysis. Med Sci Sports Exerc. 2014 Jun;46(6):1194-203. doi: 10.1249/MSS.0000000000000220.
PubMed 24576864Beaudart C, Zaaria M, Pasleau F, Reginster JY, Bruyere O. Health Outcomes of Sarcopenia: A Systematic Review and Meta-Analysis. PLoS One. 2017 Jan 17;12(1):e0169548. doi: 10.1371/journal.pone.0169548. eCollection 2017.
PubMed 28095426Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, Cooper C, Landi F, Rolland Y, Sayer AA, Schneider SM, Sieber CC, Topinkova E, Vandewoude M, Visser M, Zamboni M; Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019 Jan 1;48(1):16-31. doi: 10.1093/ageing/afy169.
PubMed 30312372
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07275996
- Acronym / sponsor ID
- MULTI-FRAIL / UBU-FB-CREHMB-CRXO-2025
- Conditions
- Frailty, Sarcopenia, Aging, Malnutrition Elderly
- Keywords
- creatine, HMB, supplementation, multicomponent exercise, concurrent training, institutionalized older adults, nursing home, physical performance
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Universidad de BurgosUniversity, hospital or other
- Study start
- 10 Mar 2026 (actual)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 30 May 2027 (estimated)
- First posted
- 10 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 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.
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 was 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Randomized, double-blind, placebo-controlled, parallel-group clinical trial with four study arms. Participants will receive 12 weeks of dietary supplementation combined with a supervised multicomponent exercise program, followed by a 3-month follow-up period without supplementation.
| Arm | Type | Receives |
|---|---|---|
| Creatine + HMB + Exercise | Experimental | Dietary Supplement: Creatine Monohydrate, Behavioral: Multicomponent Exercise Program, Dietary Supplement: β-Hydroxy-β-Methylbutyrate (HMB)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. |
| Placebo + Exercise | Placebo comparator | Dietary Supplement: Placebo (Cellulose), Behavioral: Multicomponent Exercise ProgramParticipants receive a total of 6 g/day of cellulose (placebo), administered once daily, combined with a supervised multicomponent exercise program for 12 weeks. |
| Creatine + Exercise | Active comparator | Dietary Supplement: Placebo (Cellulose), Dietary Supplement: Creatine Monohydrate, Behavioral: Multicomponent Exercise ProgramParticipants 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. |
| HMB + Exercise | Active comparator | Dietary Supplement: Placebo (Cellulose), Behavioral: Multicomponent Exercise Program, Dietary Supplement: β-Hydroxy-β-Methylbutyrate (HMB)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. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo (Cellulose)Sachets containing cellulose used as placebo filler to match supplement volume, appearance, and taste. Administered once daily, mixed with yogurt or juice, during the intervention period. | Dietary supplement | Creatine + Exercise, HMB + Exercise, Placebo + Exercise |
| Creatine MonohydrateSachets containing creatine monohydrate used as an active dietary supplement. Administered once daily during the intervention period. | Dietary supplement | Creatine + Exercise, Creatine + HMB + Exercise |
| Multicomponent Exercise ProgramSupervised exercise sessions, 4 times per week (~60 minutes each), including resistance, endurance, balance, coordination, and flexibility training. Intensity adapted to participants' functional status (Borg scale 6-9). Conducted throughout the 12-week intervention period. | Behavioural | Creatine + Exercise, Creatine + HMB + Exercise, HMB + Exercise, Placebo + Exercise |
| β-Hydroxy-β-Methylbutyrate (HMB)Sachets containing calcium β-hydroxy-β-methylbutyrate used as an active dietary supplement. Administered once daily during the intervention period. | Dietary supplement | Creatine + HMB + Exercise, HMB + Exercise |
Primary outcome
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.
29 secondary outcomes
Grip Strength
Time frame: Baseline, Week 12 (end of intervention), and 3-month follow-up
Leg and Back Isometric Strength
Time frame: Baseline, Week 12 (end of intervention), and 3-month follow-up
Seated Arm Curl Test
Time frame: Baseline, Week 12 (end of intervention), and 3-month follow-up
Barthel Index
Time frame: Baseline, Week 12 (end of intervention), and 3-month follow-up
Mini Nutritional Assessment (MNA)
Time frame: Baseline, Week 12 (end of intervention), and 3-month follow-up
Cognitive Function - Mini-Mental State Examination (MMSE)
Time frame: Baseline, Week 12 (end of intervention), and 3-month follow-up
Quality of Life - World Health Organization Quality of Life-Brief (WHOQOL-BREF)
Time frame: Baseline, Week 12 (end of intervention), and 3-month follow-up
Total Lean Mass (kg) by DEXA
Time frame: Baseline, Week 12 (end of intervention), and 3-month follow-up
Total Fat Mass (percent body weight) by DEXA
Time frame: Baseline, Week 12 (end of intervention), and 3-month follow-up
Visceral Adipose Tissue (VAT, cm³) by DEXA
Time frame: Baseline, Week 12 (end of intervention), and 3-month follow-up
Whole-Body Bone Mineral Density (BMD, g/cm²) by DEXA
Time frame: Baseline, Week 12 (end of intervention), and 3-month follow-up
Cognitive Function - MEC (Spanish Adaptation of MMSE)
Time frame: Baseline, Week 12 (end of intervention), and 3-month follow-up
Number of Falls
Time frame: Baseline to 3-month follow-up
Number of Hospitalizations
Time frame: Baseline to 3-month follow-up
Incidence of Respiratory and Urinary Infections
Time frame: Baseline to 3-month follow-up
Incidence of Pressure Ulcers
Time frame: Baseline to 3-month follow-up
Incidence of Urinary or Fecal Incontinence
Time frame: Baseline to 3-month follow-up
Serum C-reactive protein (CRP, mg/L)
Time frame: Baseline, Week 12 (end of intervention)
Interleukin-6 (IL-6, pg/mL)
Time frame: Baseline, Week 12 (end of intervention)
Tumor Necrosis Factor-alpha (TNF-α, pg/mL)
Time frame: Baseline, Week 12 (end of intervention)
Reduced Glutathione (GSH, µmol/L)
Time frame: Baseline, Week 12 (end of intervention)
Oxidized Glutathione (GSSG, µmol/L)
Time frame: Baseline, Week 12 (end of intervention)
Thiobarbituric Acid Reactive Substances (TBARS, nmol MDA equivalents/mL plasma)
Time frame: Baseline, Week 12 (end of intervention)
Malondialdehyde (MDA, µmol/L)
Time frame: Baseline, Week 12 (end of intervention)
Total Antioxidant Capacity (TAC, mmol Trolox equivalents/L)
Time frame: Baseline, Week 12 (end of intervention)
Relative expression levels of selected circulating microRNAs
Time frame: Baseline, Week 12 (end of intervention), and 3-month follow-up
Relative expression levels of selected exosome-derived microRNAs
Time frame: Baseline and Week 12
Frequency of selected genetic variants related to creatine and HMB responsiveness
Time frame: Baseline
Relative abundance of selected circulating proteins involved in muscle and inflammatory responses
Time frame: Baseline and Week 12
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2026.
- Results publication: PubMed 31845733Rezola-Pardo C, Rodriguez-Larrad A, Gomez-Diaz J, Lozano-Real G, Mugica-Errazquin I, Patino MJ, Bidaurrazaga-Letona I, Irazusta J, Gil SM. Comparison Between Multicomponent Exercise and Walking Interventions in Long-Term Nursing Homes: A Randomized Controlled Trial. Gerontologist. 2020 Sep 15;60(7):1364-1373. doi: 10.1093/geront/gnz177.
- Results publication: PubMed 31635165Fernandez-Landa J, Calleja-Gonzalez J, Leon-Guereno P, Caballero-Garcia A, Cordova A, Mielgo-Ayuso J. Effect of the Combination of Creatine Monohydrate Plus HMB Supplementation on Sports Performance, Body Composition, Markers of Muscle Damage and Hormone Status: A Systematic Review. Nutrients. 2019 Oct 20;11(10):2528. doi: 10.3390/nu11102528.
- Results publication: PubMed 31952174Fernandez-Landa J, Fernandez-Lazaro D, Calleja-Gonzalez J, Caballero-Garcia A, Cordova A, Leon-Guereno P, Mielgo-Ayuso J. Long-Term Effect of Combination of Creatine Monohydrate Plus beta-Hydroxy beta-Methylbutyrate (HMB) on Exercise-Induced Muscle Damage and Anabolic/Catabolic Hormones in Elite Male Endurance Athletes. Biomolecules. 2020 Jan 15;10(1):140. doi: 10.3390/biom10010140.
- Results publication: PubMed 31936727Fernandez-Landa J, Fernandez-Lazaro D, Calleja-Gonzalez J, Caballero-Garcia A, Cordova Martinez A, Leon-Guereno P, Mielgo-Ayuso J. Effect of Ten Weeks of Creatine Monohydrate Plus HMB Supplementation on Athletic Performance Tests in Elite Male Endurance Athletes. Nutrients. 2020 Jan 10;12(1):193. doi: 10.3390/nu12010193.
- Results publication: PubMed 28493406Holecek M. Beta-hydroxy-beta-methylbutyrate supplementation and skeletal muscle in healthy and muscle-wasting conditions. J Cachexia Sarcopenia Muscle. 2017 Aug;8(4):529-541. doi: 10.1002/jcsm.12208. Epub 2017 May 10.
- Results publication: PubMed 23327448Cadore EL, Rodriguez-Manas L, Sinclair A, Izquierdo M. Effects of different exercise interventions on risk of falls, gait ability, and balance in physically frail older adults: a systematic review. Rejuvenation Res. 2013 Apr;16(2):105-14. doi: 10.1089/rej.2012.1397.
- Results publication: PubMed 24576864Devries MC, Phillips SM. Creatine supplementation during resistance training in older adults-a meta-analysis. Med Sci Sports Exerc. 2014 Jun;46(6):1194-203. doi: 10.1249/MSS.0000000000000220.
- Results publication: PubMed 28095426Beaudart C, Zaaria M, Pasleau F, Reginster JY, Bruyere O. Health Outcomes of Sarcopenia: A Systematic Review and Meta-Analysis. PLoS One. 2017 Jan 17;12(1):e0169548. doi: 10.1371/journal.pone.0169548. eCollection 2017.
- Results publication: PubMed 30312372Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, Cooper C, Landi F, Rolland Y, Sayer AA, Schneider SM, Sieber CC, Topinkova E, Vandewoude M, Visser M, Zamboni M; Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019 Jan 1;48(1):16-31. doi: 10.1093/ageing/afy169.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) underlying the published results of this trial (including baseline characteristics and outcome measures) will be made available to qualified researchers upon reasonable request. Data will be shared only after publication of the main results and following approval of a research proposal and data access agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Juan Mielgo-Ayuso, PhD study chair
Universidad de Burgos
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Creatine Monohydrate, Multicomponent Exercise Program and β-Hydroxy-β-Methylbutyrate (HMB) in people with Frailty and Sarcopenia, run by Universidad de Burgos at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 4 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Short Physical Performance Battery (SPPB) (time frame: Baseline, Week 12 (end of intervention), and 3-month follow-up). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07275996, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2026.