Transthyretin Cardiac Amyloidosis
Conditions
Keywords
Exercise Training, Nutritional Supplementation, Creatine, Beta-Hydroxy Beta-Methylbutyrate, Older Adults, Functional Capacity, Frailty, Cardiac Amyloidosis, Transthyretin Cardiac Amyloidosis
Brief summary
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.
Interventions
OTHERUsual Care
Standard clinical management for transthyretin cardiac amyloidosis according to routine cardiology practice.
BEHAVIORALHome-Based Multicomponent Exercise Program
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.
DIETARY_SUPPLEMENTFiber Supplementation (Microcrystalline Cellulose)
Daily oral supplementation with microcrystalline cellulose, used as a nutritionally inert control supplement to match supplementation procedures.
DIETARY_SUPPLEMENTCreatine and HMB Supplementation
Daily oral supplementation with creatine monohydrate (3 g/day) and β-hydroxy-β-methylbutyrate (HMB, 3 g/day) for 12 weeks.
Sponsors
Universidad de Burgos
Hospital Universitario de Burgos
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The study is open-label. Outcome assessors are blinded to group allocation.
Intervention model description
Participants are randomly assigned to one of three parallel groups and remain in the assigned group for the duration of the study.
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥70 years. * Confirmed diagnosis of transthyretin cardiac amyloidosis (TTR-CA) based on positive bone scintigraphy with diphosphonates (Perugini grade 2 or 3) and absence of monoclonal protein. * Clinical stability during the 4 weeks prior to enrollment. * Ability to understand the study procedures and provide written informed consent.
Exclusion criteria
* Light-chain (AL) amyloidosis or other non-TTR amyloidosis variants. * Absolute medical contraindication to moderate-intensity exercise. * Severe comorbid conditions with an estimated life expectancy \<6 months. * Severe cognitive impairment (Mini-Mental State Examination score \<20). * Concurrent participation in another clinical trial or structured exercise program. * Known allergy or intolerance to creatine, beta-hydroxy-beta-methylbutyrate (HMB), or microcrystalline cellulose. * Severe renal impairment requiring dialysis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Handgrip Strength | Baseline and 12 weeks | 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. |
| Change in 6-Minute Walk Test Distance | Baseline and 12 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fat Mass | Baseline and 12 weeks | Change in total body fat mass measured in kilograms (kg) using multifrequency bioelectrical impedance analysis, expressed as the difference between baseline and 12 weeks. |
| Change in Skeletal Muscle Mass | Baseline and 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. |
| Change in Fat-Free Mass | Baseline and 12 weeks | Change in fat-free mass measured in kilograms (kg) using multifrequency bioelectrical impedance analysis, expressed as the difference between baseline and 12 weeks. |
| Change in Phase Angle | Baseline and 12 weeks | Change in phase angle measured in degrees (°) using multifrequency bioelectrical impedance analysis, expressed as the difference between baseline and 12 weeks. |
| Change in Frailty Status Assessed by the FRAIL Scale | Baseline and 12 weeks | 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. |
| All-Cause Mortality | Up to 6 months | All-cause mortality, defined as death from any cause during the follow-up period. |
| Change in Short Physical Performance Battery (SPPB) Score | Baseline and 12 weeks | 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. |
| Change in Clinical Frailty Scale (CFS) Score | Baseline and 12 weeks | 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. |
| Change in Barthel Index Score | Baseline and 12 weeks | Change in functional independence assessed by the Barthel Index, scored from 0 to 100, where higher scores indicate greater independence. |
| Change in SARC-F Score | Baseline and 12 weeks | Change in sarcopenia risk assessed by the SARC-F questionnaire, with scores ranging from 0 to 10, where higher scores indicate greater sarcopenia risk. |
| Change in Minnesota Living With Heart Failure Questionnaire Score | Baseline and 12 weeks | 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. |
| Change in Charlson Comorbidity Index | Baseline and 12 weeks | 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. |
| Incidence of Heart Failure Hospitalizations | Up to 6 months | Number of hospitalizations due to heart failure occurring during the follow-up period. |
| Incidence of Non-Heart Failure Hospitalizations | Up to 6 months | Hospital admissions due to causes other than heart failure during the follow-up period. |
| Incidence of Emergency Department Visits | Up to 6 months | Number of emergency department visits during follow-up. |
| Incidence of Intervention-Related Adverse Events | Up to 6 months | Number and type of adverse events related to exercise and/or supplementation, classified according to severity and relatedness, collected throughout the follow-up period. |
| Rate of Supplement Discontinuation | Up to 6 months | Proportion of participants who discontinue study supplements. |
| Exercise Program Adherence | Up to 12 weeks | Proportion (%) of prescribed exercise sessions completed, with adequate adherence defined as completion of at least 80% of prescribed sessions. |
| Supplement Adherence | Up to 12 weeks | Proportion (%) of planned supplement doses consumed, with optimal compliance defined as 90-110%. |
Contacts
CONTACTJuan Mielgo-Ayuso, PhD
CONTACTJosé A Pérez Rivera, PhD, MD
PRINCIPAL_INVESTIGATORJuan Mielgo-Ayuso, PhD
Universidad de Burgos
STUDY_CHAIRJosé A Pérez Rivera, PhD, MD
Hospital Universitario de Burgos
Outcome results
None listed