Fabry DiseaseFEISTYNCT05413876
Fabry Exercise Intolerance Study
An observational study of Fabry Disease and Fabry Disease, Cardiac Variant, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Fabry Disease, Fabry Disease, Cardiac Variant
- What is being tested?
- Intermittent cardiopulmonary exercise test and Incremental cardiopulmonary exercise test
- How many people
- 30 participants
- Where
- 1 siteNetherlands
- Study dates
- 10 Oct 2021to 2 Jan 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Population of FD patients, either with a classical or a non-classical phenotype. Population of healthy controls.
Who may be able to join
- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Amsterdam UMC, location AMC
Amsterdam, 1105AZ
Bram Veldman
About this study
Official title: Fabry Exercise Intolerance Study (FEISTY)
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.
Read the 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.
- Conditions
- Fabry Disease, Fabry Disease, Cardiac Variant
- Being tested
- Intermittent cardiopulmonary exercise test, Incremental cardiopulmonary exercise test
- Medical subject headings
- Fabry Disease, Fabry Disease, Cardiac Variant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intermittent cardiopulmonary exercise testOther
Exercise test with step-change from rest to a relatively low constant workload.
Incremental cardiopulmonary exercise testOther
Exercise test with incremental workload until maximal workload.
| Study group | Role | What they receive |
|---|---|---|
| Men with classical Fabry disease | Not described Receives: Other: Intermittent cardiopulmonary exercise test; Other: Incremental cardiopulmonary exercise test | |
| Women with classical Fabry disease | Not described Receives: Other: Intermittent cardiopulmonary exercise test; Other: Incremental cardiopulmonary exercise test | |
| Men with non-classical Fabry disease | Not described Receives: Other: Intermittent cardiopulmonary exercise test; Other: Incremental cardiopulmonary exercise test | |
| Healthy controls | Age-, Sex-, BMI-matched controls Receives: Other: Intermittent cardiopulmonary exercise test; Other: Incremental cardiopulmonary exercise test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Differences in V'O2 max kinetics (ml/kg/min)
Measured: At rest (baseline) and after maximum CPX test (30 min)
Tiffeneau-index (FEV1/IVC ratio)
Pulmonary involvement
Measured: At rest (baseline)
Anaerobic threshold (ml/kg/min)
Pulmonary involvement/Cardiac dysfunction/Skeletal muscle alterations
Measured: During maximum exercise (max 30 min).
Ventilation reserve (L)
Pulmonary involvement/Skeletal muscle alterations
Measured: During maximum exercise (max 30 min).
CO2 ventilation equivalent (L/L)
Pulmonary involvement/Cardiac dysfunction
Measured: During maximum exercise (max 30 min).
O2 saturation (%)
Pulmonary involvement/Cardiac dysfunction
Measured: During maximum exercise (max 30 min).
Cardiac Output (L/min)
Cardiac dysfunction
Measured: During maximum exercise (max 30 min).
Heart rate reserve (per minute)
Cardiac dysfunction:
Measured: During maximum exercise (max 30 min).
Muscle size on echography (cm)
Skeletal muscle alterations
Measured: Baseline
Muscle strength via resistance test (kg)
Skeletal muscle alterations
Measured: Biopsy at baseline
Lipidomics profile of muscle tissue
Skeletal muscle alterations
Measured: Biopsy at baseline
Electronic microscopic characteristics of muscle tissue
Skeletal muscle alterations
Measured: Biopsy at baseline
Mitochondrial function of muscle tissue
Skeletal muscle alterations
Measured: 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).
Measured: Day 1
Correlation between V'O2 kinetics during intermittent exercise and activity score on the SQUASH Questionnaire (Pearson correlation coefficient).
Measured: 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).
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2022
- Study start10 Oct 2021
- Primary completion2 Jan 2024 (estimated)
- Study completion2 Jan 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fabry DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Mirjam Langeveld, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05413876
- Sponsor's protocol ID
- NL73534.018.21
- Acronym
- FEISTY
- Status last verified
- Aug 2023
- First submitted
- 17 May 2022
- Last updated
- 24 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fabry Exercise Intolerance Study (FEISTY)
- ClinicalTrials.gov ID
- NCT05413876
- Acronym / sponsor ID
- FEISTY / NL73534.018.21
- Conditions
- Fabry Disease, Fabry Disease, Cardiac Variant
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Study start
- 10 Oct 2021 (actual)
- Primary completion
- 2 Jan 2024 (estimated)
- Study completion
- 2 Jan 2024 (estimated)
- First posted
- 10 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 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 | – | Other: Intermittent cardiopulmonary exercise test, Other: Incremental cardiopulmonary exercise testAge-, Sex-, BMI-matched controls |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Population of FD patients, either with a classical or a non-classical phenotype. Population of healthy controls.
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intermittent cardiopulmonary exercise testExercise test with step-change from rest to a relatively low constant workload. | Other | Healthy controls, Men with classical Fabry disease, Men with non-classical Fabry disease, Women with classical Fabry disease |
| Incremental cardiopulmonary exercise testExercise test with incremental workload until maximal workload. | Other | Healthy controls, Men with classical Fabry disease, Men with non-classical Fabry disease, Women with classical Fabry disease |
Primary outcome
Differences in V'O2 max kinetics (ml/kg/min)
Time frame: At rest (baseline) and after maximum CPX test (30 min)
Tiffeneau-index (FEV1/IVC ratio)
Time frame: At rest (baseline)
Pulmonary involvement
Anaerobic threshold (ml/kg/min)
Time frame: During maximum exercise (max 30 min).
Pulmonary involvement/Cardiac dysfunction/Skeletal muscle alterations
Ventilation reserve (L)
Time frame: During maximum exercise (max 30 min).
Pulmonary involvement/Skeletal muscle alterations
CO2 ventilation equivalent (L/L)
Time frame: During maximum exercise (max 30 min).
Pulmonary involvement/Cardiac dysfunction
O2 saturation (%)
Time frame: During maximum exercise (max 30 min).
Pulmonary involvement/Cardiac dysfunction
Cardiac Output (L/min)
Time frame: During maximum exercise (max 30 min).
Cardiac dysfunction
Heart rate reserve (per minute)
Time frame: During maximum exercise (max 30 min).
Cardiac dysfunction:
Muscle size on echography (cm)
Time frame: Baseline
Skeletal muscle alterations
Muscle strength via resistance test (kg)
Time frame: Biopsy at baseline
Skeletal muscle alterations
Lipidomics profile of muscle tissue
Time frame: Biopsy at baseline
Skeletal muscle alterations
Electronic microscopic characteristics of muscle tissue
Time frame: Biopsy at baseline
Skeletal muscle alterations
Mitochondrial function of muscle tissue
Time frame: Biopsy at baseline
Skeletal muscle alterations
3 secondary outcomes
Correlation between V'O2 kinetics during intermittent exercise and V'O2 max on the incremental maximum CPX (Pearson correlation coefficient).
Time frame: Day 1
Correlation between V'O2 kinetics during intermittent exercise and activity score on the SQUASH Questionnaire (Pearson correlation coefficient).
Time frame: 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).
Time frame: Day 1
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Fabry Disease and Fabry Disease, Cardiac Variant, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Bram Veldman, MD (0031205666791, b.c.f.veldman@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Differences in V'O2 max kinetics (ml/kg/min) (time frame: At rest (baseline) and after maximum CPX test (30 min)). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2023.