Neuromuscular and Multi-Omics Synergy of Combined Creatine × HMB Supplementation Plus Exercise to Improve Muscle Function in Sarcopenic Frailty
NCT ID: NCT07275996
Last Updated: 2025-12-29
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
NOT_YET_RECRUITING
NA
80 participants
INTERVENTIONAL
2026-03-10
2027-05-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
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.
Multicomponent Exercise Program
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)
Sachets containing calcium β-hydroxy-β-methylbutyrate used as an active dietary supplement. Administered once daily during the intervention period.
Creatine Monohydrate
Sachets containing creatine monohydrate used as an active dietary supplement. Administered once daily during the intervention period.
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.
Multicomponent Exercise Program
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.
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.
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.
Multicomponent Exercise Program
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.
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.
Creatine Monohydrate
Sachets containing creatine monohydrate used as an active dietary supplement. Administered once daily during the intervention period.
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.
Multicomponent Exercise Program
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)
Sachets containing calcium β-hydroxy-β-methylbutyrate used as an active dietary supplement. Administered once daily during the intervention period.
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.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Multicomponent Exercise Program
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)
Sachets containing calcium β-hydroxy-β-methylbutyrate used as an active dietary supplement. Administered once daily during the intervention period.
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.
Creatine Monohydrate
Sachets containing creatine monohydrate used as an active dietary supplement. Administered once daily during the intervention period.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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
* 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.
65 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Universidad de Burgos
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Juan Francisco Mielgo
Full Professor of Physiology, Principal Investigator
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Juan Mielgo-Ayuso, PhD
Role: STUDY_CHAIR
Universidad de Burgos
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Residencia de Mayores Fuentes Blancas (Diputación Provincial de Burgos)
Burgos, Castille and León, Spain
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Juan Mielgo-Ayuso, PhD
Role: primary
Natalia Busto, PhD
Role: backup
References
Explore related publications, articles, or registry entries linked to this study.
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.
Fernandez-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.
Fernandez-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.
Fernandez-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.
Holecek 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.
Cadore 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.
Devries 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.
Beaudart 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.
Cruz-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.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
IR 24/2023
Identifier Type: OTHER
Identifier Source: secondary_id
UBU-FB-CREHMB-CRXO-2025
Identifier Type: -
Identifier Source: org_study_id