- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05413876
Fabry Exercise Intolerance Study (FEISTY)
Fabry Exercise Intolerance Study (FEISTY)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Background: Fabry disease (FD) is an inherited, highly variable and slowly progressive X linked disorder, which predominantly affects vascular endothelium, the heart, kidneys and the brain. Exercise intolerance is a complaint expressed by the majority of patients, at all stages of the disease. The exact cause, extent and development over time of exercise intolerance in FD in insufficiently understood. This limits preventive measures and adequate treatment.
Hypothesis: 1) The development of energy metabolism in skeletal and cardiac muscle in FD is disturbed early on in disease development and this progresses as the disease worsens, resulting in reduced exercise capacity. 2) Intermittent CPX is an objective and sensitive tool to grade the level of exercise tolerance in FD patients and yields specific outcome parameters that can be used in future intervention studies.
Primary objectives: 1) To study the presence and extent of exercise intolerance in male, female FD patients with classical FD and men with non-classical FD, in different stages of the disease. 2) To determine the aetiology of exercise intolerance in FD. Secondary objectives: 1) To determine whether the exercise test protocol used in this study can be used as a clinical outcome measure in future intervention studies. 2) To investigate difference in the time-relation between V'O2 and circulatory, ventilatory and metabolic variables during intermittent exercise between FD patients groups (potentially providing an indication of the source of possibly slowed V'O2 kinetics).
Methods: This study will consist of two screening visits, one testing procedure visit, and an optional second visit for all subjects enrolled in the study. During the first testing visit two cardiopulmonary exercise (CPX) test will be performed. During the CPX tests gas exchange, ventilation, blood pressure and cardiac output will be measured and exhaustion level monitored. Before and after the tests a blood sample will be taken. The upper leg muscle strength and the leg muscle size will be assessed. In order to detect alterations in skeletal muscle energy metabolism, a needle biopsy of the upper leg muscle will be taken during the second optional study visit. In the biopsy specimen, lipidomics profile, electronic microscopic characteristics of muscle tissue and mitochondrial function will be assessed.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Bram Veldman, MD
- Phone Number: 0031205666791
- Email: b.c.f.veldman@amsterdamumc.nl
Study Locations
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-
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Amsterdam, Netherlands, 1105AZ
- Recruiting
- Amsterdam UMC, location AMC
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Contact:
- Bram Veldman
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Population of FD patients, either with a classical or a non-classical phenotype.
Population of healthy controls.
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
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:
- All abovementioned exclusion criteria for FD patients
- 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
- >6 alcohol units per day or >14 alcohol units per week
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Men with classical Fabry disease
|
Exercise test with step-change from rest to a relatively low constant workload.
Exercise test with incremental workload until maximal workload.
|
Women with classical Fabry disease
|
Exercise test with step-change from rest to a relatively low constant workload.
Exercise test with incremental workload until maximal workload.
|
Men with non-classical Fabry disease
|
Exercise test with step-change from rest to a relatively low constant workload.
Exercise test with incremental workload until maximal workload.
|
Healthy controls
Age-, Sex-, BMI-matched controls
|
Exercise test with step-change from rest to a relatively low constant workload.
Exercise test with incremental workload until maximal workload.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Differences in V'O2 max kinetics (ml/kg/min)
Time Frame: At rest (baseline) and after maximum CPX test (30 min)
|
At rest (baseline) and after maximum CPX test (30 min)
|
|
Tiffeneau-index (FEV1/IVC ratio)
Time Frame: At rest (baseline)
|
Pulmonary involvement
|
At rest (baseline)
|
Anaerobic threshold (ml/kg/min)
Time Frame: During maximum exercise (max 30 min).
|
Pulmonary involvement/Cardiac dysfunction/Skeletal muscle alterations
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During maximum exercise (max 30 min).
|
Ventilation reserve (L)
Time Frame: During maximum exercise (max 30 min).
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Pulmonary involvement/Skeletal muscle alterations
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During maximum exercise (max 30 min).
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CO2 ventilation equivalent (L/L)
Time Frame: During maximum exercise (max 30 min).
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Pulmonary involvement/Cardiac dysfunction
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During maximum exercise (max 30 min).
|
O2 saturation (%)
Time Frame: During maximum exercise (max 30 min).
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Pulmonary involvement/Cardiac dysfunction
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During maximum exercise (max 30 min).
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Cardiac Output (L/min)
Time Frame: During maximum exercise (max 30 min).
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Cardiac dysfunction
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During maximum exercise (max 30 min).
|
Heart rate reserve (per minute)
Time Frame: During maximum exercise (max 30 min).
|
Cardiac dysfunction:
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During maximum exercise (max 30 min).
|
Muscle size on echography (cm)
Time Frame: Baseline
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Skeletal muscle alterations
|
Baseline
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Muscle strength via resistance test (kg)
Time Frame: Biopsy at baseline
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Skeletal muscle alterations
|
Biopsy at baseline
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Lipidomics profile of muscle tissue
Time Frame: Biopsy at baseline
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Skeletal muscle alterations
|
Biopsy at baseline
|
Electronic microscopic characteristics of muscle tissue
Time Frame: Biopsy at baseline
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Skeletal muscle alterations
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Biopsy at baseline
|
Mitochondrial function of muscle tissue
Time Frame: Biopsy at baseline
|
Skeletal muscle alterations
|
Biopsy at baseline
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Correlation between V'O2 kinetics during intermittent exercise and V'O2 max on the incremental maximum CPX (Pearson correlation coefficient).
Time Frame: Day 1
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Day 1
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Correlation between V'O2 kinetics during intermittent exercise and activity score on the SQUASH Questionnaire (Pearson correlation coefficient).
Time Frame: Day 1
|
Day 1
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Correlation between V'O2 kinetics during intermittent exercise and functional and morphological cardiac parameters on cardiac imaging (Magnetic resonance or echocardiography) (Pearson correlation coefficient).
Time Frame: Day 1
|
Day 1
|
Other Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Body height (cm)
Time Frame: Baseline
|
Baseline
|
Body weight (kg)
Time Frame: Baseline
|
Baseline
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NT-proBNP (ng/L)
Time Frame: Baseline
|
Baseline
|
Troponin (μg/L)
Time Frame: Baseline
|
Baseline
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Lactate (mmol/L)
Time Frame: Baseline and after maximum exercise
|
Baseline and after maximum exercise
|
Haemoglobin (mmol/L)
Time Frame: Baseline
|
Baseline
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Metabolic Diseases
- Cerebrovascular Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Genetic Diseases, Inborn
- Genetic Diseases, X-Linked
- 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
- Fabry Disease
Other Study ID Numbers
- NL73534.018.21
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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