Functional Capacity in Anderson-Fabry Disease Patients

NCT06884358 | Recruiting

• 1 other identifier: OPTIMA-FD
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Anderson-Fabry Disease

Keywords

Anderson-Fabry Disease; Cardiac Involvement; CMR; CPET

Outcome Measures

Primary Outcomes (16)

• CPET parameters- peak Vo2

  Peak VO2 ml/Kg/min

  At baseline and before 36 months from baseline.

• CPET parameters- predicted peak Vo2

  Predicted peak VO2 (%).

  At baseline and before 36 months from baseline.

• CPET parameters- VE/VCO2 slope

  VE/VCO2 slope

  At baseline and before 36 months from baseline.

• CPET parameters- oxygen pulse

  02 pulse (ml/beat)

  At baseline and before 36 months from baseline.

• CPET parameters- heart rate during exercise

  Heart rate reserve (beats/minute) Heart rate recovery (beat/minute) Heart rate recovery at one minute (beat/minute)

  At baseline and before 36 months from baseline.

• CPET parameters- presence of chronotropic incompetence, O2 pulse flattening and exercise oscillatory ventilation

  Chronotropic incompetence (yes/no) 02 pulse flattening (yes/no) exercise oscillatory ventilation (yes/no)

  At baseline and before 36 months from baseline.

• CPET parameters- VO2/work slope

  VO2/work slope (ml/min/watt)

  At baseline and before 36 months from baseline.

• Echocardiogram parameters- diastolic function at rest

  At rest E/A ratio. At rest mean E/E'. At rest left atrial reservoir function (%). At rest sPAP (mmHg).

  At baseline and before 36 months from baseline.

• Echocardiogram parameters- systolic function of the left and right ventricle at rest

  At rest TAPSE (mm) At rest LV ejection fraction (%) At rest LV stroke volume indexed for body mass surface (ml/mq) At rest right ventricular free wall strain (%)

  At baseline and before 36 months from baseline.

• Echocardiogram parameters- right ventricle-pulmonary artery coupling at rest.

  At rest TAPSE/sPAP (mm/mmHg)

  At baseline and before 36 months from baseline.

• Echocardiogram parameters- exertional diastolic function

  exertional E/A, exertional mean E/E' exertional TAPE/sPAP (mm/mmHg) mPAP/CO (mmHg/L/min)

  At baseline and before 36 months from baseline.

• CMR parameters - LV Mass and LV Max Wall Thickness

  LV mass (gr) and LV max wall thickness (mm).

  At baseline and before 36 months from baseline.

• CMR parameters - Systolic Function

  Stroke volume indexed to body surface (ml/m2) and left ventricular ejection fraction (%).

  At baseline and before 36 months from baseline.

• CMR parameters - T1 and T2 Mapping

  T1 and T2 mapping (msec).

  At baseline and before 36 months from baseline.

• CMR parameters - presence of late gadolinium enhancement

  late gadolinium enhancement (yes/no)

  At baseline and before 36 months from baseline.

• CMR parameters - ECV

  Extracellular volume (%)

  At baseline and before 36 months from baseline.

Secondary Outcomes (1)

• Incidence of Cardiovascular Events

  Up to 7 years follow-up.

Study Arms (4)

Normal cardiac parameters and normal T1

AFD patients with normal cardiac parameters and normal T1.

Normal cardiac parameters and reduced T1

AFD patients with no LVH and myocardial reduced T1 .

LVH without LGE

Patients with LVH without LGE.

Advanced cardiomyopathy with LVH and LGE

AFD patients with advanced cardiomyopathy with LVH and LGE.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patient with AFD from Italian referral centers.

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• IRCCS Policlinico S. Donato: lead

Study Sites (5)

Spedali Civili Hospital

Brescia, Brescia, 25123, Italy

ACTIVE NOT RECRUITING

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Milan, 20122, Italy

ACTIVE NOT RECRUITING

IRCCS Policlinico San Donato

San Donato Milanese, Milan, 20097, Italy

RECRUITING

Fondazione IRCCS San Gerardo dei Tintori

Monza, Monza, 20900, Italy

ACTIVE NOT RECRUITING

Regina Margherita Hospital

Turin, Turin, 10124, Italy

ACTIVE NOT RECRUITING

Related Publications (7)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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. Epub 2023 Aug 2. No abstract available.

  PMID: 37542504 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Fabry Disease

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Central Study Contacts

Massimo Piepoli, MD, PhD

CONTACT

+39 0252774942; massimo.piepoli@grupposandonato.it

Gianluigi Guida, MD

CONTACT

+39 0252774942; gianluigi.guida@grupposandonato.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: January 27, 2025
• First Posted: March 19, 2025
• Study Start: November 13, 2024
• Primary Completion (Estimated): November 1, 2031
• Study Completion (Estimated): January 1, 2032
• Last Updated: March 19, 2025

Record last verified: 2025-01

Locations

IT (5)