FASHION Fabry Disease Hypertrophic Cardiomyopathy and Infammation (FASHION)

Inflammation in Anderson-Fabry Disease and Hypertrophic Cardiomyopathy: A Comparative Study (FASHION STUDY)

In Fabry disease (FD) and hypertrophic cardiomyopathy (HCM) systemic inflammation recently gained attention as a possible key pathophysiologic process involved in the development of cardiac hypertrophy and progression of the disease. Differences in inflammatory profile between FD and HCM have never been investigated so far.

Study Overview

• Status: Recruiting
• Conditions: Fabry Disease
• Intervention / Treatment: Other: Sample blood and 2D-echocardiography with Doppler

Detailed Description

This study investigate whether partecipants with FD and HCM have a different inflammatory phenotype defined by plasma biomarkers, serum proteomic profile and transcriptomic analysis in peripheral blood mononuclear cells. Moreover, the investigators sought to explore if a correlation exists between the inflammatory phenotype and the severity of cardiac phenotype cardiovascular events during 24 months of follow up.

This will be a prospective, multicenter, observational study. Adult partecipants with a genetically-proven diagnosis of FD and age-matched patients with a diagnosis of sarcomeric HCM will be enrolled, according to the following exclusion criteria:

1. Diagnosis Autoinflammatory disorders;
2. history of recurrent infections;
3. HIV infection;
4. Active cancer;
5. History of organ transplantation needing chronic immunosuppressor treatment. For each patient, at the time of enrollment, a blood sample will be collected and plasma levels of markers of inflammation, oxidative stress and cardiac remodeling will be determined (C-reactive protein, interleukin [IL]-6, IL-1β, IL-2, soluble vascular cell adhesion molecule, tumor necrosis factor [TNF], TNF receptor 1 and 2, Myeloperoxidase, calprotectin, uric acid, asymmetric dimethyl arginine, symmetric dimethyl arginine, matrix metalloprotease [MMP]-2, MMP-8 and MMP-9, galectin-1, galectin-3, B-type natriuretic peptide, midregional pro-atrial natriuretic peptide, monocyte chemoattractant protein.

Serum proteomic analysis and transcriptomic analysis on peripheral blood mononuclear cells, investigating molecular mediators involved in inflammatory pathways will be also performed. Partecipants enrolled will also undergo a comprehensive 2D-echocardiography with Doppler, Tissue Doppler (TD) and speckle tracking analysis and 12-leads electrocardiogram.

• Study Type: Observational
• Enrollment (Anticipated): 150

Contacts and Locations

• Study Contact: Name: GIOVANNA GL LIUZZO; Phone Number: +39 0630154187; Email: giovanna.liuzzo@policlinicogemelli.it

Study Locations

• Italy
  • Roma, Italy, 00168
    • Recruiting
    • Fondazione Policlinico Gemelli

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Adult patients with a genetically-proven diagnosis of FD and age-matched patients with a diagnosis of sarcomeric HCM will be enrolled.

The spectrum of cardiomyopathies with hypertrophic phenotype encompasses heterogeneous diseases, including classic hypertrophic cardiomyopathy (HCM), due to sarcomere protein gene mutations, and several diseases mimicking HCM, such as Fabry cardiomyopathy.

Description

Inclusion Criteria:

• Age ≥18 years;
• Patients with confirmed genetic diagnosis of FD19;
• Patients with a known diagnosis of sarcomeric HCM adult (with pathogenic mutation in sarcomeric genes identified);
• Signed informed consent.

Exclusion Criteria:

• Age <18 years;
• Diagnosis of Autoinflammatory disorders;
• History of recurrent infections;
• HIV infection;
• Active cancer;
• History of organ transplantation needing chronic immunosuppressor treatment;
• Pregnancy
• Refusal to sign informed consent to study participation.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Partecipants with Fabry Desease (FD); For each patient, at the time of enrollment, a blood sample will be collected and plasma levels of markers of inflammation, oxidative stress and cardiac remodeling will be determined (C-reactive protein, interleukin [IL]-6, IL-1β, IL-2, soluble vascular cell adhesion molecule, tumor necrosis factor [TNF], TNF receptor 1 and 2, Myeloperoxidase, calprotectin, uric acid, asymmetric dimethyl arginine, symmetric dimethyl arginine, matrix metalloprotease [MMP]-2, MMP-8 and MMP-9, galectin-1, galectin-3, B-type natriuretic peptide, midregional pro-atrial natriuretic peptide, monocyte chemoattractant protein-1). Serum proteomic analysis and transcriptomic analysis on peripheral blood mononuclear cells, investigating molecular mediators involved in inflammatory pathways will be also performed. Patients enrolled will also undergo a comprehensive 2D-echocardiography with Doppler, Tissue Doppler (TD) and speckle tracking analysis and 12-leads electrocardiogram.	Other: Sample blood and 2D-echocardiography with Doppler; Investigate whether patients with FD and HCM have a different inflammatory phenotype defined by plasma biomarkers, serum proteomic profile and transcriptomic analysis in peripheral blood mononuclear cells.; Other Names: Tissue Doppler (TD) and speckle tracking analysis and 12-leads electrocardiogram.
Partecipants with hypertrophic cardiomyopathy (HCM) systemic inflammation; For each patient, at the time of enrollment, a blood sample will be collected and plasma levels of markers of inflammation, oxidative stress and cardiac remodeling will be determined (C-reactive protein, interleukin [IL]-6, IL-1β, IL-2, soluble vascular cell adhesion molecule, tumor necrosis factor [TNF], TNF receptor 1 and 2, Myeloperoxidase, calprotectin, uric acid, asymmetric dimethyl arginine, symmetric dimethyl arginine, matrix metalloprotease [MMP]-2, MMP-8 and MMP-9, galectin-1, galectin-3, B-type natriuretic peptide, midregional pro-atrial natriuretic peptide, monocyte chemoattractant protein-1). Serum proteomic analysis and transcriptomic analysis on peripheral blood mononuclear cells, investigating molecular mediators involved in inflammatory pathways will be also performed. Patients enrolled will also undergo a comprehensive 2D-echocardiography with Doppler, Tissue Doppler (TD) and speckle tracking analysis and 12-leads electrocardiogram.	Other: Sample blood and 2D-echocardiography with Doppler; Investigate whether patients with FD and HCM have a different inflammatory phenotype defined by plasma biomarkers, serum proteomic profile and transcriptomic analysis in peripheral blood mononuclear cells.; Other Names: Tissue Doppler (TD) and speckle tracking analysis and 12-leads electrocardiogram.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigate the inflammatory phenotype of patients with FD and patients with HCM	Primary objective of the study is to investigate the inflammatory phenotype of patients with FD and patients with HCM. For each partecipants enrolled the investigators will record information about demographic and clinic data (age, gender, weight, height, hypertension, GLA gene mutation, sarcomeric genes mutation), conventional pharmacological therapy and specific therapy for FD patients such as Enzyme Replacement Therapy (α or β algasidase) or oral chaperon therapy (when it was started, therapeutic compliance).	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between the inflammatory phenotype and clinical, ECG and echocardiographic features, in both the diseases	Explore whether a correlation exists between the inflammatory phenotype and clinical, ECG and echocardiographic features, in both the diseases. Investigate the relationship between the inflammatory phenotype and the occurrence of MACEs (Major Adverse Cardiovascular Events, cardiovascular death, hospitalization for HF, new-onset atrial fibrillation, evolution to end-stage phase, sustained ventricular arrhythmias and/or bradyarrhythmias requiring pacemaker implantation, heart transplantation) during 24 months of follow-up in FD and HCM.	1 year

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2023
• Primary Completion (Anticipated): July 27, 2023
• Study Completion (Anticipated): January 10, 2025

Study Registration Dates

• First Submitted: February 16, 2023
• First Submitted That Met QC Criteria: February 27, 2023
• First Posted (Estimate): March 9, 2023

Study Record Updates

• Last Update Posted (Estimate): March 9, 2023
• Last Update Submitted That Met QC Criteria: February 27, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Hypertophic Cardiomyopathy
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Aortic Valve Disease; Heart Valve Diseases; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Cardiomyopathies; Fabry Disease; Cardiomyopathy, Hypertrophic
• Other Study ID Numbers: 4756

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No