An interventional study of Creatine monohydrate and Beta-hydroxy-beta-methylbutyrate (HMB) in Huntington Disease, Sarcopenia and Frailty, sponsored by Universidad de Burgos. Not yet recruiting at 1 site in Spain. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-28.
Sponsored by Universidad de Burgos · Not applicable, Interventional, and Treatment
Huntington's disease (HD) is a rare neurodegenerative disorder in which accelerated loss of muscle mass, strength and autonomy (physical frailty and sarcopenia) contributes to functional decline. This randomized, double-blind, placebo-controlled, four-arm parallel trial will include adults with HD and physical frailty/sarcopenia. All participants will follow a 12-week individualized, home-based multicomponent exercise program (VIVIFRAIL-based, with weekly remote monitoring) and will be randomized 1:1:1:1 to placebo, creatine (CRE), beta-hydroxy-beta-methylbutyrate (HMB) or combined CRE+HMB. The study will test whether combined CRE+HMB produces synergistic improvements in functional capacity, neuromuscular performance, body composition, cognition and quality of life, and will use multi-omic profiling (circulating and extracellular-vesicle microRNAs, plasma proteomics and genetics) to identify mechanisms and predictive signatures of response. Durability of effects will be assessed 6 months after the end of the intervention.
Design: randomized, double-blind, placebo-controlled, four-arm parallel-group trial conducted at the Neurology Department of Hospital Universitario de Burgos (HUBU; recruitment, clinical assessment, biological sampling) and the University of Burgos (UBU; exercise physiology, functional testing and multi-omic analyses).
Randomization: computer-generated permuted blocks of variable size (REDCap), 1:1:1:1 allocation, stratified by sex, antipsychotic use, participation in structured exercise programs and diabetes. Allocation is performed and concealed by an independent pharmacist (HUBU Pharmacy Service). Participants, intervention staff, outcome assessors and data analysts are blinded; supplements are packed in identical coded sachets.
Interventions: once daily for 12 weeks, dissolved in 100 mL fruit juice with the evening meal: (1) 3 g creatine monohydrate + 3 g microcrystalline cellulose; (2) 3 g beta-hydroxy-beta-methylbutyrate (HMB) + 3 g cellulose; (3) 3 g creatine + 3 g HMB; (4) placebo, 6 g microcrystalline cellulose. All participants follow a Mediterranean-style diet (protein 1.2-1.5 g/kg/day) and an individualized home-based multicomponent exercise program based on VIVIFRAIL, prescribed and supervised by an occupational therapist, with weekly phone calls to monitor adherence, perceived exertion (target Borg rating of perceived exertion [RPE] 12-15) and adverse events. Adherence is monitored by intake logs and sachet counts.
Assessments: baseline (T0), week 12 (T1, end of intervention) and 6-month follow-up (T2). Functional capacity (Unified Huntington's Disease Rating Scale [UHDRS] Total Functional Capacity [TFC], Functional Assessment Scale, Independence Scale, gait speed, Short Physical Performance Battery [SPPB]), body composition (multifrequency bioimpedance), neuromuscular function (rate of force development and peak force during isometric knee extension), cognition (Mini-Mental State Examination [MMSE], Symbol Digit Modalities Test [SDMT], Stroop test, Trail Making Test [TMT], verbal fluency), quality of life (12-Item Short Form Health Survey [SF-12]) and adverse events. Fasting blood samples for small RNA sequencing (RNA-seq) of circulating and extracellular-vesicle microRNAs (with quantitative polymerase chain reaction [qPCR] validation), plasma proteomics (Olink Reveal, 1,034 proteins) and pharmacogenetics (15 single nucleotide polymorphisms [SNPs] in SLC6A8, CKM, GATM, MTOR, AKT1, PTEN; genome-wide genotyping in a subset).
Sample size: 64 participants (16 per arm) are needed to detect a small-to-moderate effect (f = 0.20) on change in TFC (alpha 0.05, power 0.80, r = 0.50); allowing for 25-30% dropout, 84-88 participants will be enrolled.
Statistical analysis: intention-to-treat and per-protocol analyses; linear mixed-effects models with Group x Time interaction and pre-specified contrasts of creatine (CRE)+HMB versus each single supplement and placebo; multi-omic integration (mixOmics/DIABLO, MOFA+, elastic net, random forest) with repeated nested cross-validation to identify predictive signatures of response.
293 studies on the registry are indexed under Huntington Disease; 54 are open to participants now.
This study's planned enrollment of 88 is above the median of 40 across 207 interventional studies indexed under Huntington Disease.
Browse Huntington Disease studies →Universidad de Burgos is the lead sponsor of 25 studies on the registry; 4 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Placebo (6 g/day microcrystalline cellulose) for 12 weeks plus the individualized home-based multicomponent exercise program.
Dietary Supplement: Placebo (microcrystalline cellulose) · Behavioral: Home-based multicomponent exercise program
3 g/day creatine monohydrate + 3 g/day microcrystalline cellulose for 12 weeks plus the individualized home-based multicomponent exercise program.
Dietary Supplement: Creatine monohydrate · Behavioral: Home-based multicomponent exercise program
3 g/day beta-hydroxy-beta-methylbutyrate (HMB) + 3 g/day microcrystalline cellulose for 12 weeks plus the individualized home-based multicomponent exercise program.
Dietary Supplement: Beta-hydroxy-beta-methylbutyrate (HMB) · Behavioral: Home-based multicomponent exercise program
3 g/day creatine monohydrate + 3 g/day beta-hydroxy-beta-methylbutyrate (HMB) for 12 weeks plus the individualized home-based multicomponent exercise program.
Dietary Supplement: Creatine monohydrate · Dietary Supplement: Beta-hydroxy-beta-methylbutyrate (HMB) · Behavioral: Home-based multicomponent exercise program
3 g/day creatine monohydrate (with 3 g microcrystalline cellulose when given alone, or with 3 g beta-hydroxy-beta-methylbutyrate (HMB) in the combined arm), dissolved in 100 mL fruit juice and taken once daily with the evening meal for 12 weeks, in identical coded sachets.
3 g/day HMB (with 3 g microcrystalline cellulose when given alone, or with 3 g creatine monohydrate in the combined arm), dissolved in 100 mL fruit juice and taken once daily with the evening meal for 12 weeks, in identical coded sachets.
6 g/day microcrystalline cellulose, suspended in 100 mL fruit juice and taken once daily with the evening meal for 12 weeks, in sachets identical in appearance to the active supplements.
12-week individualized home-based multicomponent exercise program (strength, balance, gait and endurance) based on VIVIFRAIL, adapted to Huntington's disease (HD)-specific motor and cognitive limitations, prescribed and supervised by an occupational therapist, with weekly training logs and phone calls to monitor adherence, perceived exertion (target Borg rating of perceived exertion \[RPE\] 12-15) and adverse events. All participants also receive Mediterranean-style dietary advice (protein 1.2-1.5 g/kg/day).
Change in Total Functional Capacity (TFC)
Unified Huntington's Disease Rating Scale (UHDRS) Total Functional Capacity score, range 0-13; higher scores indicate better functional capacity. Change from baseline will be compared across the four arms.
Time frame: Baseline, week 12 (end of intervention) and 6 months after the end of intervention
Change in Functional Assessment Scale (FAS)
UHDRS Functional Assessment Scale, 25 yes/no items, range 0-25; higher scores indicate better function.
Time frame: Baseline, week 12 (end of intervention) and 6 months after the end of intervention
Change in Independence Scale (IS)
UHDRS Independence Scale, range 10-100 in 5-point steps; higher scores indicate greater independence.
Time frame: Baseline, week 12 (end of intervention) and 6 months after the end of intervention
Change in Gait Speed
Usual gait speed (m/s) measured over a standardized walking course.
Time frame: Baseline, week 12 (end of intervention) and 6 months after the end of intervention
Change in Rate of Force Development (RFD) 0-200 ms
Rate of force development (RFD) from 0 to 200 ms (N/s) during maximal isometric knee extension measured with a force transducer (best of three 5-s trials).
Time frame: Baseline, week 12 (end of intervention) and 6 months after the end of intervention
Change in Peak Force
Peak force (N) during maximal isometric knee extension measured with a force transducer (best of three 5-s trials).
Time frame: Baseline, week 12 (end of intervention) and 6 months after the end of intervention
Change in Contraction Time
Contraction time (ms) during maximal isometric knee extension measured with a force transducer (best of three 5-s trials).
Time frame: Baseline, week 12 (end of intervention) and 6 months after the end of intervention
Change in Fat-Free Mass (FFM)
Fat-free mass (FFM, kg) assessed by multifrequency bioelectrical impedance analysis (BIA).
Time frame: Baseline, week 12 (end of intervention) and 6 months after the end of intervention
Change in Fat Mass (FM)
Fat mass (FM, kg) assessed by multifrequency bioelectrical impedance analysis (BIA).
Time frame: Baseline, week 12 (end of intervention) and 6 months after the end of intervention
Change in Fat-Free Mass Index (FFMI)
Fat-free mass index (FFMI, kg/m\^2) assessed by multifrequency bioelectrical impedance analysis (BIA).
Time frame: Baseline, week 12 (end of intervention) and 6 months after the end of intervention
Change in Fat Mass Index (FMI)
Fat mass index (FMI, kg/m\^2) assessed by multifrequency bioelectrical impedance analysis (BIA).
Time frame: Baseline, week 12 (end of intervention) and 6 months after the end of intervention
Change in Mini-Mental State Examination (MMSE) Score
MMSE total score, range 0-30; higher scores indicate better global cognitive function. Part of the Enroll-HD cognitive battery.
Time frame: Baseline, week 12 (end of intervention) and 6 months after the end of intervention
Change in Symbol Digit Modalities Test (SDMT), Oral Version
Number of correct responses in 90 seconds on the oral version of the SDMT; higher scores indicate better performance. Part of the Enroll-HD cognitive battery.
Time frame: Baseline, week 12 (end of intervention) and 6 months after the end of intervention
Change in Stroop Test Performance
Number of correct responses in 45 seconds on the Stroop test; higher scores indicate better performance. Part of the Enroll-HD cognitive battery.
Time frame: Baseline, week 12 (end of intervention) and 6 months after the end of intervention
Change in Trail Making Test Part A (TMT-A) Completion Time
Time to complete Trail Making Test Part A (seconds); lower values indicate better performance. Part of the Enroll-HD cognitive battery.
Time frame: Baseline, week 12 (end of intervention) and 6 months after the end of intervention
Change in Trail Making Test Part B (TMT-B) Completion Time
Time to complete Trail Making Test Part B (seconds); lower values indicate better performance. Part of the Enroll-HD cognitive battery.
Time frame: Baseline, week 12 (end of intervention) and 6 months after the end of intervention
Change in Semantic Verbal Fluency
Number of words produced in 60 seconds in a semantic (category) verbal fluency task; higher scores indicate better performance. Part of the Enroll-HD cognitive battery.
Time frame: Baseline, week 12 (end of intervention) and 6 months after the end of intervention
Change in Phonemic Verbal Fluency
Number of words produced in 60 seconds in a phonemic (letter) verbal fluency task; higher scores indicate better performance. Part of the Enroll-HD cognitive battery.
Time frame: Baseline, week 12 (end of intervention) and 6 months after the end of intervention
Change in 12-Item Short Form Health Survey (SF-12) Physical Component Summary (PCS)
SF-12 Physical Component Summary score, range 0-100; higher scores indicate better physical health-related quality of life.
Time frame: Baseline, week 12 (end of intervention) and 6 months after the end of intervention
Change in 12-Item Short Form Health Survey (SF-12) Mental Component Summary (MCS)
SF-12 Mental Component Summary score, range 0-100; higher scores indicate better mental health-related quality of life.
Time frame: Baseline, week 12 (end of intervention) and 6 months after the end of intervention
Number of Participants With Adverse Events and Falls
Adverse events and serious adverse events (including falls, emergency visits and hospitalizations) related or unrelated to supplementation, exercise or blood sampling; causality assessed with the Spanish Pharmacovigilance System algorithm.
Time frame: From informed consent until 30 days after the end of supplementation (week 16), plus clinically relevant events up to 6 months after the end of intervention
Change in Circulating and Extracellular-Vesicle microRNA Profiles
Plasma circulating and extracellular-vesicle-associated microRNAs (e.g., miR-1, miR-133, miR-206, miR-146a, miR-21, miR-34a) quantified by small RNA sequencing (RNA-seq; normalized counts) with quantitative polymerase chain reaction (qPCR) validation.
Time frame: Baseline, week 12 (end of intervention) and 6 months after the end of intervention
Change in Plasma Proteomic Profile
Relative abundance, expressed as Normalized Protein eXpression (NPX) values, of 1,034 plasma proteins related to inflammation, immune response and muscle repair (e.g., interleukin-6 \[IL-6\], tumor necrosis factor-alpha \[TNF-alpha\], C-reactive protein \[CRP\]) measured with the Olink Reveal proximity extension assay.
Time frame: Baseline, week 12 (end of intervention) and 6 months after the end of intervention
Genetic Polymorphisms as Moderators of Response
Genotypes of 15 single nucleotide polymorphisms (SNPs) in creatine transport/metabolism and mechanistic target of rapamycin (mTOR)-related genes (SLC6A8, CKM, GATM, MTOR, AKT1, PTEN) by TaqMan qPCR, and genome-wide genotyping (Axiom Spain Biobank Array) in a subset, analyzed as moderators of functional and neuromuscular response.
Time frame: Single blood sample during the study (baseline, week 12 or 6-month follow-up)
Change in Short Physical Performance Battery (SPPB)
SPPB total score (0-12; higher scores indicate better physical performance), including balance, 4-m gait speed and 5-times chair stand tests. Exploratory functional outcome.
Time frame: Baseline, week 12 (end of intervention) and 6 months after the end of intervention
Plan to share: Yes — De-identified individual participant data underlying the published results will be shared upon reasonable request to the principal investigators.
Time frame: After publication of the main results, for 5 years.
Access criteria: Researchers submitting a methodologically sound proposal approved by the principal investigators, subject to a data sharing agreement and applicable data protection regulations (General Data Protection Regulation [GDPR]).
No publications or documents are linked to this record.
Start is estimated for Nov 2026; primary completion for Dec 2028, 25 months later.
Of 33 interventional studies with no phase under Huntington Disease, half reached primary completion within 32 months of starting (the median), counting those still running; a quarter within 19 and three quarters within 36. This study's planned 25 months is below that.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Creatine monohydrate · Beta-hydroxyisovaleric acid
Universidad de Burgos