Fabry Exercise Intolerance Study

NCT05413876 | Unknown DMC

• 1 other identifier: NL73534.018.21
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Patients and healthy controls will undergo cardiopulmonary exercises and testing of the muscles strength to gain additional understanding of exercise intolerance as Fabry disease (FD) manifestation. An additional needle muscle biopsy may be performed. Tissue analysis from this biopsy will include evaluation of the lipidomics profile and mitochondrial function. Results of the tests and any potential exercise intolerance will be compared against healthy, age-, sex- and BMI-matched volunteers. The hypothesis is that patients with FD will have reduced exercise capacity due to changes in skeletal and cardiac muscle energy metabolism.

Conditions

Fabry Disease; Fabry Disease, Cardiac Variant

Outcome Measures

Primary Outcomes (13)

• Differences in V'O2 max kinetics (ml/kg/min)

  At rest (baseline) and after maximum CPX test (30 min)

• Tiffeneau-index (FEV1/IVC ratio)

  Pulmonary involvement

  At rest (baseline)

• Anaerobic threshold (ml/kg/min)

  Pulmonary involvement/Cardiac dysfunction/Skeletal muscle alterations

  During maximum exercise (max 30 min).

• Ventilation reserve (L)

  Pulmonary involvement/Skeletal muscle alterations

  During maximum exercise (max 30 min).

• CO2 ventilation equivalent (L/L)

  Pulmonary involvement/Cardiac dysfunction

  During maximum exercise (max 30 min).

• O2 saturation (%)

  Pulmonary involvement/Cardiac dysfunction

  During maximum exercise (max 30 min).

• Cardiac Output (L/min)

  Cardiac dysfunction

  During maximum exercise (max 30 min).

• Heart rate reserve (per minute)

  Cardiac dysfunction:

  During maximum exercise (max 30 min).

• Muscle size on echography (cm)

  Skeletal muscle alterations

  Baseline

• Muscle strength via resistance test (kg)

  Skeletal muscle alterations

  Biopsy at baseline

• Lipidomics profile of muscle tissue

  Skeletal muscle alterations

  Biopsy at baseline

• Electronic microscopic characteristics of muscle tissue

  Skeletal muscle alterations

  Biopsy at baseline

• Mitochondrial function of muscle tissue

  Skeletal muscle alterations

  Biopsy at baseline

Secondary Outcomes (3)

• Correlation between V'O2 kinetics during intermittent exercise and V'O2 max on the incremental maximum CPX (Pearson correlation coefficient).

  Day 1

• Correlation between V'O2 kinetics during intermittent exercise and activity score on the SQUASH Questionnaire (Pearson correlation coefficient).

  Day 1

• Correlation between V'O2 kinetics during intermittent exercise and functional and morphological cardiac parameters on cardiac imaging (Magnetic resonance or echocardiography) (Pearson correlation coefficient).

  Day 1

Other Outcomes (6)

• Body height (cm)

  Baseline

• Body weight (kg)

  Baseline

• NT-proBNP (ng/L)

  Baseline

Study Arms (4)

Men with classical Fabry disease

Other: Intermittent cardiopulmonary exercise test; Other: Incremental cardiopulmonary exercise test

Women with classical Fabry disease

Other: Intermittent cardiopulmonary exercise test; Other: Incremental cardiopulmonary exercise test

Men with non-classical Fabry disease

Other: Intermittent cardiopulmonary exercise test; Other: Incremental cardiopulmonary exercise test

Healthy controls

Age-, Sex-, BMI-matched controls

Other: Intermittent cardiopulmonary exercise test; Other: Incremental cardiopulmonary exercise test

Interventions

Intermittent cardiopulmonary exercise test OTHER

Exercise test with step-change from rest to a relatively low constant workload.

Healthy controls; Men with classical Fabry disease; Men with non-classical Fabry disease; Women with classical Fabry disease

Incremental cardiopulmonary exercise test OTHER

Exercise test with incremental workload until maximal workload.

Healthy controls; Men with classical Fabry disease; Men with non-classical Fabry disease; Women with classical Fabry disease

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Population of FD patients, either with a classical or a non-classical phenotype. Population of healthy controls.

You may qualify if:

• FD patients: Men and women with a definite known diagnosis of FD.
• Healthy controls: Healthy control subjects (men and women) with an age of 18 years of older.

You may not qualify if:

• FD patients:
• Pregnancy
• Recent acute myocardial infarct (\<6 months)
• Uncontrolled arrhythmia/severe conduction disorder (atrial fibrillation or second/third-degree AV block) causing hemodynamic compromise
• Implantable pacemaker or other cardiac device with complete ventricular pacing
• Uncontrolled heart failure with hemodynamic compromise
• Uncontrolled hypertension (Systolic Blood Pressure \>150 mmHg and Diastolic Blood Pressure \>100 mmHg on repeated measurements)
• Active infection, anaemia, severe renal dysfunction (estimated Glomerular filtration rate \<30 ml/min/1,73m2) likely to significantly impact on exercise performance
• In some cases: use of anticoagulants or anti platelet therapy (see study procedure)
• Healthy controls:
• History of smoking
• History of active drug use which can affect exercise intolerance
• History of asthma, chronic obstructive pulmonary disease, heart failure, heart surgery, heart rhythm disorders or congenital heart diseases
• Use of chronic medication likely to affect exercise tolerance
• Chronic illness (including orthopaedic, endocrinological, haematological, malignant, gastrointestinal, neurological, muscle or inflammatory disorders) likely to significantly impact on exercise performance

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (1)

Amsterdam UMC, location AMC

Amsterdam, 1105AZ, Netherlands

RECRUITING

MeSH Terms

Conditions

Fabry Disease; Fabry Disease, Cardiac Variant

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

Bram Veldman, MD

CONTACT

0031205666791; b.c.f.veldman@amsterdamumc.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 17, 2022
• First Posted: June 10, 2022
• Study Start: October 10, 2021
• Primary Completion: January 2, 2024
• Study Completion: January 2, 2024
• Last Updated: August 24, 2023

Record last verified: 2023-08

Locations

NL (1)