Neuromuscular and Multi-Omics Synergy of Combined Creatine × HMB Supplementation Plus Exercise to Improve Muscle Function in Sarcopenic Frailty

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 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.

Conditions

• Frailty
• Sarcopenia
• Aging
• Malnutrition Elderly

Interventions

DIETARY_SUPPLEMENT

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 Monohydrate

Sachets containing creatine monohydrate used as an active dietary supplement. Administered once daily during the intervention period.

BEHAVIORAL

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.

DIETARY_SUPPLEMENT

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.

Sponsors & Collaborators

• Universidad de Burgos

  lead OTHER

Principal Investigators

• Juan Mielgo-Ayuso, PhD · Universidad de Burgos

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-03-10

Primary Completion

2026-12-30

Completion

2027-05-30

Countries

• Spain

Study Locations