Sarcopenia
Conditions
Brief summary
Sarcopenia is an age-related condition characterized by loss of muscle strength and physical performance, leading to increased risk of falls and disability. This randomized, double-blind, placebo-controlled clinical trial aims to evaluate the effects of ursolic acid-standardized apple pomace supplementation on muscle strength and physical performance in older adults with mild sarcopenia. Participants will be randomly assigned to receive either 200 mg/day, 400 mg/day of the supplement, or placebo for 12 weeks. The primary outcome is change in handgrip strength, with additional assessments of physical performance, body composition, fatigue, and quality of life. The study will also evaluate the safety and tolerability of the intervention.
Detailed description
Sarcopenia is an age-related skeletal muscle disorder characterized by progressive decline in muscle strength and physical performance, resulting in increased risk of falls, disability, and loss of independence. Despite its clinical relevance, no pharmacological therapies are currently approved, and management relies primarily on exercise and nutritional strategies, which may be insufficient or impractical for many individuals. Ursolic acid is a naturally occurring triterpenoid found in apple peel and other plant sources, with preclinical evidence demonstrating beneficial effects on skeletal muscle mass, strength, and metabolic function. These effects have been linked to modulation of anabolic signaling pathways, including insulin and insulin-like growth factor-1 pathways, as well as suppression of muscle atrophy-related genes. Human studies remain limited, particularly in older adults with sarcopenia. This study is a randomized, double-blind, placebo-controlled, parallel-group clinical trial designed to evaluate the effects of ursolic acid-standardized apple pomace extract formulated with phospholipids on muscle strength and physical performance in older adults with mild sarcopenia. A total of 105 participants will be randomized in a 1:1:1 ratio to receive either 200 mg/day, 400 mg/day of the active supplement, or placebo for 12 weeks. The primary endpoint is change in handgrip strength from baseline to Week 6 and Week 12. Key secondary endpoints include measures of lower-limb functional strength and physical performance, including five-times chair stand test, Short Physical Performance Battery score, gait speed, and Timed Up and Go test. Additional outcomes include body composition assessed by bioelectrical impedance analysis, patient-reported outcomes such as fatigue and health-related quality of life, and safety assessments including adverse events and laboratory parameters. The study is conducted in accordance with Good Clinical Practice and the Declaration of Helsinki, and aims to provide clinical evidence on the efficacy and safety of ursolic acid supplementation in a population with clinically relevant muscle function impairment.
Interventions
DIETARY_SUPPLEMENTUrsolic Acid-Standardized Apple Pomace Extract
Oral supplementation with ursolic acid-standardized apple pomace extract formulated with phospholipids. The product is standardized to contain triterpenes including ursolic acid and is administered as tablets.
OTHERPlacebo
Matching placebo tablets identical in appearance, taste, and packaging to the active supplement, administered orally.
Sponsors
Liaquat University of Medical & Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This is a double-blind study in which participants, care providers, investigators, and outcome assessors are blinded to treatment allocation. Study products and placebo are identical in appearance, packaging, and administration schedule. Unblinding is permitted only in case of medical necessity.
Intervention model description
Participants will be randomized in a 1:1:1 ratio to receive either 200 mg/day ursolic acid-standardized apple pomace supplementation, 400 mg/day supplementation, or placebo for 12 weeks. Each participant will remain in their assigned group throughout the study period.
Eligibility
Sex/Gender
ALL
Age
65 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age 65 to 80 years (inclusive) * Male or female * Community-dwelling outpatients * Able and willing to provide written informed consent * Able to comply with study procedures and attend scheduled visits * Able to walk independently (assistive devices permitted) and safely perform physical performance assessments * Stable medical condition and stable medication regimen for at least 4 weeks prior to screening * Mild sarcopenia defined as: * SARC-F score ≥4 or clinical suspicion of sarcopenia, and Low muscle strength defined as: Handgrip strength \<27 kg for men or \<16 kg for women, or Five-times chair stand test \>15 seconds or inability to complete without use of arms \- Eligible for body composition assessment using bioelectrical impedance analysis (BIA)
Exclusion criteria
* Severe sarcopenia or severe functional impairment precluding safe participation * Unstable or uncontrolled medical conditions that may interfere with participation or safety * Severe renal or hepatic disease, including: * eGFR \<30 mL/min/1.73 m² * Significant liver disease or markedly abnormal liver function tests * Uncontrolled endocrine or metabolic disorders * Active malignancy or ongoing cancer treatment * Use of medications affecting muscle mass or function, including: * Chronic systemic corticosteroids * Anabolic steroids or testosterone therapy * Other investigational muscle-modifying agents * Recent structured resistance training within the past 3 months * Use of muscle-targeted supplements (e.g., creatine, HMB) within the previous 4-8 weeks * Contraindications to BIA (e.g., pacemaker or implanted electronic device) * Acute illness within 4 weeks prior to screening * Cognitive impairment preventing informed consent or protocol compliance * Known allergy or intolerance to ursolic acid or study product components * Any condition that, in the opinion of the investigator, may compromise safety, compliance, or data integrity
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in handgrip strength from baseline | Baseline to Week 12 | Handgrip strength will be measured in kilograms using a calibrated hand dynamometer. The best value from three attempts on the dominant hand in a standardized seated position will be recorded. The outcome represents the change from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in five-times chair stand test time | Baseline to Week 12 | Time in seconds required to complete five consecutive chair stands without use of the arms, assessed as change from baseline. |
| Change in Short Physical Performance Battery (SPPB) score | Baseline to Week 12 | Total SPPB score (range 0-12) assessing lower extremity function, including balance, gait speed, and chair stand performance, evaluated as change from baseline. |
| Change in gait speed | Baseline to Week 12 | Usual gait speed measured over a 4-meter walk test, expressed in meters per second and evaluated as change from baseline. |
| Change in Timed Up and Go test time | Baseline to Week 12 | Time in seconds required to stand from a chair, walk 3 meters, turn, return, and sit down, assessed as change from baseline. |
| Change in body composition | Baseline to Week 12 | Body composition parameters assessed by bioelectrical impedance analysis, including skeletal muscle mass, skeletal muscle index, and fat mass, evaluated as change from baseline. |
| Change in fatigue severity | Baseline to Week 12 | Fatigue severity assessed using a validated fatigue severity scale, evaluated as change from baseline. |
| Change in health-related quality of life | Baseline to Week 12 | Health-related quality of life assessed using the SF-12 physical and mental component summary scores, evaluated as change from baseline. |
Countries
Pakistan
Outcome results
None listed