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| Name | Class |
|---|---|
| Hospital Universitario de Burgos | OTHER |
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Transthyretin cardiac amyloidosis (TTR-CA) is a heart disease that mainly affects older adults and often leads to reduced physical capacity, muscle weakness, frailty, and a decline in quality of life. While current medical treatments can slow disease progression, they do not fully address functional limitations or muscle deterioration.
The EFICAC-TTR study is a prospective, randomized, multicenter clinical trial designed to evaluate whether a combined non-pharmacological intervention can improve physical function in patients aged 70 years or older with confirmed TTR-CA.
A total of 102 participants will be randomly assigned to one of three groups: (1) usual medical care, (2) a home-based multicomponent exercise program combined with fiber supplementation, or (3) the same exercise program combined with creatine monohydrate and β-hydroxy-β-methylbutyrate (HMB) supplementation. The exercise program is adapted to each participant's functional level and is performed at home.
The main outcomes of the study are changes in walking capacity, measured by the 6-minute walk test, and muscle strength, assessed by handgrip strength after 12 weeks. Secondary outcomes include changes in body composition, frailty, quality of life, and clinical events, while mechanistic biomarkers are assessed as exploratory outcomes.
This study aims to determine whether combining exercise with nutritional supplementation can safely improve functional capacity and overall health in older adults with transthyretin cardiac amyloidosis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Usual Care | Other | Participants receive usual medical care for transthyretin cardiac amyloidosis, including routine cardiology follow-up and general lifestyle recommendations, without structured exercise or nutritional supplementation. |
|
| Exercise + Fiber Supplementation (Active Control) | Placebo Comparator | Participants perform a home-based multicomponent exercise program and receive daily supplementation with microcrystalline cellulose, used as a nutritionally inert control supplement. |
|
| Exercise + Creatine and HMB Supplementation | Experimental | Participants perform a home-based multicomponent exercise program and receive daily supplementation with creatine monohydrate (3 g/day) and β-hydroxy-β-methylbutyrate (HMB, 3 g/day). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Usual Care | Other | Standard clinical management for transthyretin cardiac amyloidosis according to routine cardiology practice. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Handgrip Strength | Change in maximal isometric handgrip strength measured in kilograms (kg) using a calibrated handheld dynamometer (best of three attempts for the dominant hand), expressed as the difference between baseline and 12 weeks. | Baseline and 12 weeks |
| Change in 6-Minute Walk Test Distance | Change in walking capacity assessed by the 6-minute walk test, measured as the difference in total distance walked (meters) between baseline and 12 weeks. | Baseline and 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Fat Mass | Change in total body fat mass measured in kilograms (kg) using multifrequency bioelectrical impedance analysis, expressed as the difference between baseline and 12 weeks. | Baseline and 12 weeks |
| Change in Skeletal Muscle Mass |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Growth Differentiation Factor 15 (GDF-15) | Change in serum GDF-15 concentration (pg/mL) measured by immunoassay. | Baseline and 12 weeks |
| Change in Soluble ST2 | Change in serum soluble ST2 concentration (ng/mL) measured by immunoassay. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Juan Mielgo-Ayuso, PhD | Contact | +34 947 25 87 00 | jmielgo@ubu.es | |
| José A Pérez Rivera, PhD, MD | Contact | +34 947 28 19 64 | jangel.perezrivera@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Juan Mielgo-Ayuso, PhD | Universidad de Burgos | Principal Investigator |
| José A Pérez Rivera, PhD, MD | Hospital Universitario de Burgos | Study Chair |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31081853 | Result | 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 Jul 1;48(4):601. doi: 10.1093/ageing/afz046. No abstract available. | |
| 41073834 |
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De-identified individual participant data that underlie the results reported in publications will be made available upon reasonable request.
Beginning 6 months after publication and ending 5 years after publication.
Access to de-identified individual participant data will be granted upon reasonable request to the principal investigator. Requests must include a methodologically sound research proposal and will be evaluated for scientific merit and feasibility. Data sharing will require the execution of a data sharing agreement and will comply with applicable data protection and privacy regulations.
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Participants are randomly assigned to one of three parallel groups and remain in the assigned group for the duration of the study.
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The study is open-label. Outcome assessors are blinded to group allocation.
| Home-Based Multicomponent Exercise Program | Behavioral | A 12-week home-based multicomponent exercise program adapted from the Vivifrail model, including strength, balance, mobility, and endurance exercises tailored to individual functional capacity. |
|
| Fiber Supplementation (Microcrystalline Cellulose) | Dietary Supplement | Daily oral supplementation with microcrystalline cellulose, used as a nutritionally inert control supplement to match supplementation procedures. |
|
| Creatine and HMB Supplementation | Dietary Supplement | Daily oral supplementation with creatine monohydrate (3 g/day) and β-hydroxy-β-methylbutyrate (HMB, 3 g/day) for 12 weeks. |
|
Change in skeletal muscle mass measured in kilograms (kg) using multifrequency bioelectrical impedance analysis, expressed as the difference between baseline and 12 weeks.
| Baseline and 12 weeks |
| Change in Fat-Free Mass | Change in fat-free mass measured in kilograms (kg) using multifrequency bioelectrical impedance analysis, expressed as the difference between baseline and 12 weeks. | Baseline and 12 weeks |
| Change in Phase Angle | Change in phase angle measured in degrees (°) using multifrequency bioelectrical impedance analysis, expressed as the difference between baseline and 12 weeks. | Baseline and 12 weeks |
| Change in Frailty Status Assessed by the FRAIL Scale | Change in frailty status assessed by the FRAIL scale, a 5-item questionnaire with scores ranging from 0 to 5, where higher scores indicate greater frailty, expressed as the difference between baseline and 12 weeks. | Baseline and 12 weeks |
| All-Cause Mortality | All-cause mortality, defined as death from any cause during the follow-up period. | Up to 6 months |
| Change in Short Physical Performance Battery (SPPB) Score | Change in Short Physical Performance Battery (SPPB) total score, ranging from 0 to 12 points, where higher scores indicate better physical performance, expressed as the difference between baseline and 12 weeks. | Baseline and 12 weeks |
| Change in Clinical Frailty Scale (CFS) Score | Change in frailty severity assessed by the Clinical Frailty Scale (CFS), a 9-point ordinal scale ranging from 1 (very fit) to 9 (terminally ill), where higher scores indicate greater frailty. | Baseline and 12 weeks |
| Change in Barthel Index Score | Change in functional independence assessed by the Barthel Index, scored from 0 to 100, where higher scores indicate greater independence. | Baseline and 12 weeks |
| Change in SARC-F Score | Change in sarcopenia risk assessed by the SARC-F questionnaire, with scores ranging from 0 to 10, where higher scores indicate greater sarcopenia risk. | Baseline and 12 weeks |
| Change in Minnesota Living With Heart Failure Questionnaire Score | Change in health-related quality of life assessed by the Minnesota Living With Heart Failure Questionnaire (MLHFQ), with total scores ranging from 0 to 105, where higher scores indicate worse quality of life. | Baseline and 12 weeks |
| Change in Charlson Comorbidity Index | Change in comorbidity burden assessed using the Charlson Comorbidity Index, a weighted index that accounts for the number and severity of comorbid conditions, where higher scores indicate greater comorbidity burden. | Baseline and 12 weeks |
| Incidence of Heart Failure Hospitalizations | Number of hospitalizations due to heart failure occurring during the follow-up period. | Up to 6 months |
| Incidence of Non-Heart Failure Hospitalizations | Hospital admissions due to causes other than heart failure during the follow-up period. | Up to 6 months |
| Incidence of Emergency Department Visits | Number of emergency department visits during follow-up. | Up to 6 months |
| Incidence of Intervention-Related Adverse Events | Number and type of adverse events related to exercise and/or supplementation, classified according to severity and relatedness, collected throughout the follow-up period. | Up to 6 months |
| Rate of Supplement Discontinuation | Proportion of participants who discontinue study supplements. | Up to 6 months |
| Exercise Program Adherence | Proportion (%) of prescribed exercise sessions completed, with adequate adherence defined as completion of at least 80% of prescribed sessions. | Up to 12 weeks |
| Supplement Adherence | Proportion (%) of planned supplement doses consumed, with optimal compliance defined as 90-110%. | Up to 12 weeks |
| Baseline and 12 weeks |
| Change in Interleukin-6 (IL-6) | Change in serum interleukin-6 (IL-6) concentration (pg/mL) measured by immunoassay. | Baseline and 12 weeks |
| Change in C-Reactive Protein (CRP) | Change in serum C-reactive protein (CRP) concentration (mg/L) measured by immunoassay. | Baseline and 12 weeks |
| Change in circulating miR-21 expression | Change in circulating miR-21 expression measured by quantitative PCR, expressed as relative expression (ΔΔCt). | Baseline and 12 weeks |
| Change in circulating miR-29 expression | Change in circulating miR-29 expression measured by quantitative PCR, expressed as relative expression (ΔΔCt). | Baseline and 12 weeks |
| Change in circulating miR-34a expression | Change in circulating miR-34a expression measured by quantitative PCR, expressed as relative expression (ΔΔCt). | Baseline and 12 weeks |
| Change in circulating miR-155 expression | Change in circulating miR-155 expression measured by quantitative PCR, expressed as relative expression (ΔΔCt). | Baseline and 12 weeks |
| Change in PBMC Macrophage Polarization (M1/M2) by Flow Cytometry | Change in macrophage polarization profile assessed by flow cytometry immunophenotyping of PBMC-derived macrophages, expressed as M1/M2 ratio. | Baseline and 12 weeks |
| Change in Pro-inflammatory (M1) Gene Expression Markers | Change in gene expression of predefined pro-inflammatory (M1) markers in PBMC-derived macrophages, measured by quantitative PCR and expressed as relative expression (ΔΔCt). | Baseline and 12 weeks |
| Change in Anti-inflammatory (M2) Gene Expression Markers | Change in gene expression of predefined anti-inflammatory (M2) markers in PBMC-derived macrophages, measured by quantitative PCR and expressed as relative expression (ΔΔCt). | Baseline and 12 weeks |
| Result |
| Ramos-Hernandez R, Miguel-Ortega A, Martinez-Ferran M, Fernandez-Lazaro D, Busto N, Mielgo-Ayuso J. Combined creatine and HMB co-supplementation improves functional strength independent of muscle mass in physically active older adults: a randomized crossover trial. Geroscience. 2025 Oct 10. doi: 10.1007/s11357-025-01889-y. Online ahead of print. |
| 30592475 | Result | de Souto Barreto P, Rolland Y, Vellas B, Maltais M. Association of Long-term Exercise Training With Risk of Falls, Fractures, Hospitalizations, and Mortality in Older Adults: A Systematic Review and Meta-analysis. JAMA Intern Med. 2019 Mar 1;179(3):394-405. doi: 10.1001/jamainternmed.2018.5406. |
| 33825853 | Result | Garcia-Pavia P, Rapezzi C, Adler Y, Arad M, Basso C, Brucato A, Burazor I, Caforio ALP, Damy T, Eriksson U, Fontana M, Gillmore JD, Gonzalez-Lopez E, Grogan M, Heymans S, Imazio M, Kindermann I, Kristen AV, Maurer MS, Merlini G, Pantazis A, Pankuweit S, Rigopoulos AG, Linhart A. Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2021 Apr 21;42(16):1554-1568. doi: 10.1093/eurheartj/ehab072. |
| 31171094 | Result | Ruberg FL, Grogan M, Hanna M, Kelly JW, Maurer MS. Transthyretin Amyloid Cardiomyopathy: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019 Jun 11;73(22):2872-2891. doi: 10.1016/j.jacc.2019.04.003. |
| ID | Term |
|---|---|
| D000073496 | Frailty |
| D028227 | Amyloid Neuropathies, Familial |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D009422 | Nervous System Diseases |
| D017772 | Amyloid Neuropathies |
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D028226 | Amyloidosis, Familial |
| D008661 | Metabolism, Inborn Errors |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D000686 | Amyloidosis |
| D057165 | Proteostasis Deficiencies |
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| ID | Term |
|---|---|
| C109691 | microcrystalline cellulose |
| D003401 | Creatine |
| ID | Term |
|---|---|
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
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