RCTJadad 5/5RandomizedDouble-BlindPlacebo-Controlled
Test Title
GeroScienceOctober 10, 2025Vol. 48 (3)
Summary
Test summary.
What This Means For You
Test implications.
Important Considerations
Test caveats.
Terms Explained
AB
Technical Study Details
Study Design
Duration15 weeks
RegistrationClinicalTrials.gov: NCT05951439
Total Score
JADAD Quality Assessment5
/ 5評価詳細
Randomization
2 / 2Is the study described as randomized?
Yes+1
Rationale: The article explicitly and repeatedly describes the study as a "randomized, double-blind, placebo-controlled crossover trial" in both the abstract and methods sections, and further details the randomization procedure (computer-generated allocation sequence, 1:1 ratio, prepared by an independent researcher), clearly satisfying the criterion for this Jadad item.
Is the method of randomization described and appropriate?
Yes+1
Rationale: The article explicitly describes the randomization method as a computer-generated allocation sequence with a 1:1 ratio, prepared by an independent researcher not involved in recruitment, data collection, or analysis. Computer-generated randomization is a well-recognized, appropriate method for allocation sequence generation, satisfying the Jadad criterion for Q2.
Blinding
2 / 2Is the study described as double-blind?
Yes+1
Rationale: The article repeatedly and explicitly describes the trial design as "randomized, double-blind, placebo-controlled crossover trial" in both the Abstract and Methods sections, and further specifies that both participants and research team members were blinded to group allocation.
Is the method of blinding described and appropriate?
Yes+1
Rationale: The article explicitly describes the blinding method: supplements (CRE+HMB) and placebo were prepared in identical, opaque, coded sachets by an independent third party, with the placebo being isocaloric (6 g inulin-based) and matched in total weight/preparation/administration method (mixed with yogurt or fruit juice, taken once daily) to the active supplement (3 g CRE + 3 g HMB = 6 g total). This ensures participants and researchers could not distinguish between conditions, meeting the criteria for an appropriate double-blinding method (identical appearance/packaging, matched dosing format, isocaloric placebo).
Dropouts/Withdrawals
1 / 1Is there a description of dropouts and withdrawals?
Yes+1
Rationale: The article explicitly reports the number of participants who did not enroll (7 of 40) and the reason (declined to stop other supplementation or ineligibility), and the number who withdrew during the study (3) along with the reason (personal reasons), explicitly noting none withdrew due to adverse effects. It also reports the final completing sample size (30) and overall attrition rate (10%). Because this is a crossover trial where all participants were assigned to receive both conditions, withdrawal counts/reasons are reported for the overall trial population rather than as two separate parallel arms, but the criterion of describing numbers and reasons for withdrawals is satisfied.</rationale>
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Study Population
Sample Size30
Age Range60-82 years
ConditionAge-related risk of sarcopenia / functional decline in physically active older adults
Inclusion Criteria
- Age ≥ 60 years
- Physically active (engaging in at least 150 min of moderate activity per week)
- Free from severe cardiovascular, renal, hepatic or musculoskeletal disorders
Interventions
Creatine monohydrate + HMB
TreatmentDose3 g creatine monohydrate + 3 g HMB (free acid form) = 6 g total per sachet
FrequencyOnce daily, ~30 min before bedtime, mixed with yogurt or fruit juice
Duration6 weeks per intervention period
Routeoral
Isocaloric inulin-based placebo
ControlDose6 g per sachet
FrequencyOnce daily, ~30 min before bedtime, mixed with yogurt or fruit juice
Duration6 weeks per intervention period
Routeoral
Integral Physical Conditioning (IPC) program
TreatmentFrequency4 supervised sessions/week, 60 min each
Duration6-week blocks (two blocks separated by 3-week washout)
Outcomes
| Outcome | Type | Effect | p-value |
|---|---|---|---|
| Handgrip strength | Primary | - | - |
| Isometric leg and back strength | Primary | - | - |
| Isometric arm flexion strength (1RM) | Primary | - | - |
| 30-s dumbbell arm flexion test | Primary | - | - |
| 30-s push-up test | Primary | - | - |
| 30-s crunch test (core endurance) | Primary | - | -Significant |
| Isometric pull-up hold | Primary | - | - |
| Fat mass | Primary | - | p<0.05 (time×group interaction)Significant |
| Body fat percentage | Secondary | - | - |
| Fat-free mass | Primary | - | p<0.05 (time×group interaction)Significant |
| Total muscle mass | Primary | - | p<0.05 (time×group interaction)Significant |
| Skeletal muscle mass | Primary | - | p<0.05 (time×group interaction)Significant |
| Appendicular skeletal muscle mass (ALM) | Primary | - | p<0.05 (time×group interaction)Significant |
| Muscle mass index (MMI) | Primary | - | p<0.05 (time×group interaction)Significant |
| Skeletal muscle index (SMI) | Primary | - | p<0.05 (time×group interaction)Significant |
| ALM/BMI | Primary | - | p<0.05 (time×group interaction)Significant |
Safety
Serious AEs0
Dropout Rate9.1%
Conclusion
Six weeks of CRE + HMB supplementation combined with an Integral Physical Conditioning (IPC) program significantly improved functional strength and muscular endurance (leg/back strength, arm flexion strength, upper-body endurance, and core endurance) in physically active older adults. These improvements were largely independent of changes in skeletal muscle mass or sarcopenia-related indices (except grip strength), suggesting neuromuscular/functional adaptations rather than hypertrophy predominantly drove the gains. This combined nutritional-exercise strategy represents a promising approach for preserving functional capacity, promoting autonomy and supporting healthy ageing, though larger and more diverse trials with longer follow-up are needed to confirm findings and clarify underlying mechanisms.Limitations
- Sex-stratified subgroups (20 men, 10 women) were underpowered to detect sex-specific effects and should be interpreted with caution.
- The a priori sample size calculation was based on grip strength as a single representative endpoint and did not formally adjust for multiplicity across the family of co-primary endpoints, potentially reducing effective statistical power.
- Body composition was assessed via bioelectrical impedance analysis (BIA), which has inherent limitations in capturing subtle muscle mass changes compared with gold-standard methods such as DXA.
- Relatively short intervention duration (6-week periods) and absence of long-term follow-up limit conclusions about sustainability of effects.
- Absence of separate creatine-only or HMB-only arms precludes determining the individual contribution of each supplement to observed outcomes.
- Minor logistical protocol deviations (training schedule, recruitment site, timing of assessments) were introduced during the trial, though documented via a ClinicalTrials.gov protocol update and reported not to affect primary outcomes.
- No direct neuromuscular measurements (e.g., electromyography, muscle biopsies) were performed, preventing confirmation of the proposed neural adaptation mechanisms underlying the functional strength improvements.