Functional Capacity in Anderson-Fabry Disease Patients

Official title

FunctiOnal caPaciTy Evaluation Using cardIopulMonary Testing and Stress echocArdiography in Anderson-Fabry Disease Patients: OPTIMA-FD Study

Overview

The goal of this observational study is to observe the relation between excercise parameters - assessed by CPET - and rest/stress hemodynamic parameters - assessed by echocardiogram and CMR - in patients with a genetic diagnosis of Anderson-Fabry Disease. Participants will undergo: * baseline evaluation: clinical evaluation, disease staging with FASTEX and MSSI, KCCQ for quality of life assessment, resting 12-leads ECG, 6MWT, CPET-ESE and contrast-enhanced CMR; * before 36 months from baseline: resting 12-leads ECG, 2D rest and stress echocardiogram, CPET-ESE, contrast-enhanced CMR, disease staging with FASTEX and MSSI and KCCQ for quality of life assessment; * up to 7 years from baseline: clinical follow-up.

Primary outcome measures

• CPET parameters- peak Vo2 [Time frame: At baseline and before 36 months from baseline.]
• CPET parameters- predicted peak Vo2 [Time frame: At baseline and before 36 months from baseline.]
• CPET parameters- VE/VCO2 slope [Time frame: At baseline and before 36 months from baseline.]
• CPET parameters- oxygen pulse [Time frame: At baseline and before 36 months from baseline.]
• CPET parameters- heart rate during exercise [Time frame: At baseline and before 36 months from baseline.]
• CPET parameters- presence of chronotropic incompetence, O2 pulse flattening and exercise oscillatory ventilation [Time frame: At baseline and before 36 months from baseline.]
• CPET parameters- VO2/work slope [Time frame: At baseline and before 36 months from baseline.]
• Echocardiogram parameters- diastolic function at rest [Time frame: At baseline and before 36 months from baseline.]
• Echocardiogram parameters- systolic function of the left and right ventricle at rest [Time frame: At baseline and before 36 months from baseline.]
• Echocardiogram parameters- right ventricle-pulmonary artery coupling at rest. [Time frame: At baseline and before 36 months from baseline.]

Secondary outcome measures (1)

• Incidence of Cardiovascular Events [Time frame: Up to 7 years follow-up.]

Eligibility criteria

Inclusion criteria

• Patients with a genetic diagnosis of AFD, according to current guidelines;
• Informed written consent with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care (for patients age <18 years old, written consent from a caregiver is mandatory).

Exclusion criteria

• eGFR <30 ml/min and other contraindications for CMR (relative controindication: patients with implantable device);
• Musculoskeletal limitation for exercise test on the cyclo ergometer;
• Pregnant or breastfeeding women;
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with a full comprehension of the written consent form.

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

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Italy · 5 centers

• Spedali Civili Hospital — Brescia
• Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico — Milan
• IRCCS Policlinico San Donato — San Donato Milanese
• Fondazione IRCCS San Gerardo dei Tintori — Monza
• Regina Margherita Hospital — Turin

Publications

• Linhart A, Germain DP, Olivotto I, Akhtar MM, Anastasakis A, Hughes D, Namdar M, Pieroni M, Hagege A, Cecchi F, Gimeno JR, Limongelli G, Elliott P. An expert consensus document on the management of cardiovascular manifestations of Fabry disease. Eur J Heart Fail. 2020 Jul;22(7):1076-1096. doi: 10.1002/ejhf.1960. Epub 2020 Aug 14. PMID 32640076
• Reant P, Testet E, Reynaud A, Bourque C, Michaud M, Rooryck C, Goizet C, Lacombe D, de-Precigout V, Peyrou J, Cochet H, Lafitte S. Characterization of Fabry Disease cardiac involvement according to longitudinal strain, cardiometabolic exercise test, and T1 mapping. Int J Cardiovasc Imaging. 2020 Jul;36(7):1333-1342. doi: 10.1007/s10554-020-01823-7. Epub 2020 May 8. PMID 32385539
• Bierer G, Kamangar N, Balfe D, Wilcox WR, Mosenifar Z. Cardiopulmonary exercise testing in Fabry disease. Respiration. 2005 Sep-Oct;72(5):504-11. doi: 10.1159/000087675. PMID 16210890
• Lobo T, Morgan J, Bjorksten A, Nicholls K, Grigg L, Centra E, Becker G. Cardiovascular testing in Fabry disease: exercise capacity reduction, chronotropic incompetence and improved anaerobic threshold after enzyme replacement. Intern Med J. 2008 Jun;38(6):407-14. doi: 10.1111/j.1445-5994.2008.01669.x. PMID 18613897
• Ditaranto R, Leone O, Lovato L, Niro F, Cenacchi G, Papa V, Baldovini C, Ferracin M, Salamon I, Kurdi H, Parisi V, Capelli I, Pession A, Liguori R, Potena L, Seri M, Martin Suarez S, Galie N, Moon JC, Biagini E. Correlations Between Cardiac Magnetic Resonance and Myocardial Histologic Findings in Fabry Disease. JACC Cardiovasc Imaging. 2023 Dec;16(12):1629-1632. doi: 10.1016/j.jcmg.2023.06.011. Ep PMID 37542504
• Linhart A, Elliott PM. The heart in Anderson-Fabry disease and other lysosomal storage disorders. Heart. 2007 Apr;93(4):528-35. doi: 10.1136/hrt.2005.063818. No abstract available. PMID 17401074
• Pieroni M, Moon JC, Arbustini E, Barriales-Villa R, Camporeale A, Vujkovac AC, Elliott PM, Hagege A, Kuusisto J, Linhart A, Nordbeck P, Olivotto I, Pietila-Effati P, Namdar M. Cardiac Involvement in Fabry Disease: JACC Review Topic of the Week. J Am Coll Cardiol. 2021 Feb 23;77(7):922-936. doi: 10.1016/j.jacc.2020.12.024. PMID 33602475

Identifiers

NCT: NCT06884358 · OPTIMA-FD

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗