EFICAC-TTR Trial: Exercise and Nutritional Supplementation in Transthyretin Cardiac Amyloidosis

Official title

A Prospective, Randomized, Multicenter Clinical Trial on the Effect of a Home-Based Multicomponent Exercise Program Combined With Nutritional Supplementation in Patients With Transthyretin Cardiac Amyloidosis

Overview

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

• Other Usual Care
  Standard clinical management for transthyretin cardiac amyloidosis according to routine cardiology practice.
• Behavioral Home-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 supplement Fiber Supplementation (Microcrystalline Cellulose)
  Daily oral supplementation with microcrystalline cellulose, used as a nutritionally inert control supplement to match supplementation procedures.
• Dietary supplement Creatine and HMB Supplementation
  Daily oral supplementation with creatine monohydrate (3 g/day) and β-hydroxy-β-methylbutyrate (HMB, 3 g/day) for 12 weeks.

Primary outcome measures

• Change in Handgrip Strength [Time frame: Baseline and 12 weeks]
• Change in 6-Minute Walk Test Distance [Time frame: Baseline and 12 weeks]

Secondary outcome measures (12)

• Change in Fat Mass [Time frame: Baseline and 12 weeks]
• Change in Skeletal Muscle Mass [Time frame: Baseline and 12 weeks]
• Change in Fat-Free Mass [Time frame: Baseline and 12 weeks]
• Change in Phase Angle [Time frame: Baseline and 12 weeks]
• Change in Frailty Status Assessed by the FRAIL Scale [Time frame: Baseline and 12 weeks]
• All-Cause Mortality [Time frame: Up to 6 months]
• Change in Short Physical Performance Battery (SPPB) Score [Time frame: Baseline and 12 weeks]
• Change in Clinical Frailty Scale (CFS) Score [Time frame: Baseline and 12 weeks]
• Change in Barthel Index Score [Time frame: Baseline and 12 weeks]
• Change in SARC-F Score [Time frame: Baseline and 12 weeks]
• Change in Minnesota Living With Heart Failure Questionnaire Score [Time frame: Baseline and 12 weeks]
• Change in Charlson Comorbidity Index [Time frame: Baseline and 12 weeks]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• 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( PMID 31081853
• 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. PMID 41073834
• 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. PMID 30592475
• 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 Pericard PMID 33825853
• 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. PMID 31171094

Identifiers

NCT: NCT07343999 · EFICAC-TTR-UBU-HUBU

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗