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

NCT07343999 | Completed

• 1 other identifier: EFICAC-TTR-UBU-HUBU
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 3

Brief Summary

Transthyretin cardiac amyloidosis (TTR-CA) is a systemic cardiac disease that predominantly affects older adults and is frequently associated with reduced physical capacity, muscle weakness, frailty, and impaired quality of life. Although disease-modifying treatments can slow cardiac disease progression, functional and nutritional impairment remain important unmet clinical needs. EFICAC-TTR is a prospective, randomized, multicenter study designed to evaluate the effects of a 12-week home-based multicomponent exercise program combined with nutritional supplementation in adults aged 70 years or older with confirmed TTR-CA. A total of 47 participants were randomized to one of three parallel groups: (1) usual medical care; (2) a home-based multicomponent exercise program plus microcrystalline cellulose control supplementation; or (3) the same exercise program plus creatine monohydrate (3 g/day) and beta-hydroxy-beta-methylbutyrate (HMB, 3 g/day). The primary functional outcomes are change in 6-minute walk test distance and handgrip strength from baseline to 12 weeks. Secondary outcomes include body composition, frailty, quality of life, and nutritional and clinical variables. Mechanistic biomarkers are assessed as exploratory outcomes. The study aims to determine whether combining exercise with nutritional supplementation can improve functional capacity and related health outcomes in older adults with TTR-CA.

Conditions

Transthyretin Cardiac Amyloidosis

Keywords

Exercise Training; Nutritional Supplementation; Creatine; Beta-Hydroxy Beta-Methylbutyrate; Older Adults; Functional Capacity; Frailty; Cardiac Amyloidosis; Transthyretin Cardiac Amyloidosis

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (17)

• Change in Fat Mass

  Baseline and 12 weeks

• Change in Skeletal Muscle Mass

  Baseline and 12 weeks

• Change in Fat-Free Mass

  Baseline and 12 weeks

• Change in Phase Angle

  Baseline and 12 weeks

• Change in Frailty Status Assessed by the FRAIL Scale

  Baseline and 12 weeks

Other Outcomes (21)

• Change in Growth Differentiation Factor 15 (GDF-15)

  Baseline and 12 weeks

• Change in Soluble ST2

  Baseline and 12 weeks

• Change in Interleukin-6 (IL-6)

  Baseline and 12 weeks

Study Arms (3)

Usual Care

OTHER

Participants received usual medical care for transthyretin cardiac amyloidosis, including routine cardiology follow-up and general lifestyle and nutritional recommendations, without the structured study exercise program or study supplementation.

Other: Usual Care

Exercise + Microcrystalline Cellulose Control Supplementation

PLACEBO COMPARATOR

Participants performed a 12-week home-based multicomponent exercise program and received daily microcrystalline cellulose as the control supplement. The supplement was provided in sachets matched to the supplementation procedure used in the experimental arm.

Behavioral: Home-Based Multicomponent Exercise Program; Dietary Supplement: Microcrystalline Cellulose Control Supplementation

Exercise + Creatine and HMB Supplementation

EXPERIMENTAL

Participants performed the same 12-week home-based multicomponent exercise program and received daily supplementation with creatine monohydrate (3 g/day) and beta-hydroxy-beta-methylbutyrate (HMB, 3 g/day).

Behavioral: Home-Based Multicomponent Exercise Program; Dietary Supplement: Creatine and HMB Supplementation

Interventions

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.

Exercise + Creatine and HMB Supplementation; Exercise + Microcrystalline Cellulose Control Supplementation

Usual Care OTHER

Standard clinical management for transthyretin cardiac amyloidosis according to routine cardiology practice.

Usual Care

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.

Exercise + Creatine and HMB Supplementation

Microcrystalline Cellulose Control Supplementation DIETARY_SUPPLEMENT

Daily oral supplementation with microcrystalline cellulose, used as a nutritionally inert control supplement to match supplementation procedures.

Exercise + Microcrystalline Cellulose Control Supplementation

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Universidad de Burgos: lead
• Hospital Universitario de Burgos: collaborator

Study Sites (3)

Hospital Santos Reyes

Aranda de Duero, Castille and León, Spain

Location

Hospital Universitario de Burgos

Burgos, Castille and León, 09006, Spain

Location

Hospital Santa Bárbara

Soria, Castille and León, Spain

Location

Related Publications (5)

• 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.

  PMID: 31081853 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. 2026 Jun;48(3):4457-4475. doi: 10.1007/s11357-025-01889-y. Epub 2025 Oct 10.

  PMID: 41073834 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.

  PMID: 30592475 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.

  PMID: 33825853 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.

  PMID: 31171094 RESULT

MeSH Terms

Conditions

Frailty; Amyloid Neuropathies, Familial

Interventions

Creatine

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Amyloid Neuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amyloidosis, Familial; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Amyloidosis; Proteostasis Deficiencies

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Juan Mielgo-Ayuso, PhD

  Universidad de Burgos

  STUDY DIRECTOR

• José A Pérez Rivera, PhD, MD

  Hospital Universitario de Burgos

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The comparison between usual care and the exercise groups was necessarily open-label because of the nature of the behavioral intervention. Within the two exercise groups, participants received indistinguishable supplement sachets containing either creatine plus HMB or microcrystalline cellulose. Outcome assessors were blinded to treatment allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants were randomly assigned to one of three parallel groups: usual care, home-based multicomponent exercise plus microcrystalline cellulose control supplementation, or the same exercise program plus creatine and HMB supplementation. Participants remained in their assigned group throughout the 12-week intervention.

Study Record Dates

• First Submitted: December 17, 2025
• First Posted: January 15, 2026
• Study Start: February 3, 2026
• Primary Completion: September 10, 2026
• Study Completion: September 10, 2026
• Last Updated: September 25, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 6 months after publication and ending 5 years after publication.
• Access Criteria: 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.

Locations

ES (3)