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Exercise Intolerance Study in Long Chain Fatty Acid Oxidation Disorders (EXCITE LcFAOD)

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ClinicalTrials.gov Identifier: NCT05924555
Recruitment Status : Not yet recruiting
First Posted : June 29, 2023
Last Update Posted : June 29, 2023
Sponsor:
Collaborator:
Stichting Stofwisselkracht
Information provided by (Responsible Party):
Dr. Mirjam Langeveld, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Tracking Information
First Submitted Date June 21, 2023
First Posted Date June 29, 2023
Last Update Posted Date June 29, 2023
Estimated Study Start Date August 1, 2023
Estimated Primary Completion Date August 1, 2028   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: June 21, 2023)
  • 1. Differences in V'O2/ V'CO2/heart rate kinetics during the intermittent exercise test between LcFAOD patients and healthy control subjects [ Time Frame: At rest (baseline) and during the intermittent CPX test (30 min) ]
  • 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
  • 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: Baseline ]
    Skeletal muscle alterations
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Exercise Intolerance Study in Long Chain Fatty Acid Oxidation Disorders
Official Title Exercise Intolerance Study in Long Chain Fatty Acid Oxidation Disorders
Brief Summary In this study, the exercise tolerance in patients with long-chain fatty acid oxidation disorders (LcFAOD) will be compared to that of healthy volunteers who are carefully matched in terms of age, sex, BMI and physical activity score. The study aims to assess exercise capacity using cardiopulmonary exercise (CPX) tests and activity monitoring over a 7-day period. The hypothesis of the study is that LcFAOD patients will exhibit greater oxygen debt during short periods of exercise compared to healthy individuals. These findings will contribute to a better understanding of exercise intolerance in LcFAOD patients and may guide the development of targeted interventions, such as exercise training programs and enable the analysis of effectiveness of (new) treatments.
Detailed Description

Background:Long-chain fatty acid oxidation disorders (LcFAOD) are a group of autosomal recessive disorders that impair the utilization of long-chain fatty acids as an energy source. Exercise intolerance is a commonly reported symptom in adult patients with LcFAOD, but its severity varies significantly among individuals. In addition, little is currently known about the natural progression of exercise intolerance in this group of patients, and reliable outcome measures to assess treatment efficacy remain scarce. In this study, we will evaluate the exercise capacity in LcFAOD patients using intermittent CPX, and determine whether this yields outcome parameters that can be used to determine the course of exercise intolerance over the patients lifetime and evaluate treatment effectiveness.

Hypothesis: Exercise intolerance in LcFAOD patients will be reflected in differences in VO2/VCO2 and heart rate kinetics during short periods of exercise compared to healthy subjects.

Primary Objective: 1. Objectify and quantify exercise intolerance in LcFAOD patients. 2. Determine the relationship between the measured exercise intolerance and patient-reported symptoms, daily life functioning, as well as known markers of disease severity.

Secondary Objective(s): 3. Determine the aetiology of exercise intolerance in LcFAODs. 4. Determine whether the intermittent exercise protocol can be used to establish the course of exercise intolerance and provide clinical outcome measure for future intervention studies.

Methods: Participants will be asked to wear an activity monitor (Activ8) for a period of 7 days. The participants will also perform two cardiopulmonary exercise (CPX) tests (one intermittent and one incremental). During the CPX tests gas exchange, ventilation, blood pressure and cardiac output will be measured and exhaustion level monitored. Blood samples will be taken before the first and after the second CPX test. The grip strength (Maximal Voluntary Contraction) and the leg muscle size (echography) will be assessed. Body composition (using BIA) will be assessed.

Approximately a year later all procedures, including the wearing of the activity monitor, will be repeated in all patients. Some participants will be asked to perform the two exercise tests again within two weeks of their first visit. This way reproducibility of the intermittent exercise protocol can be tested.

Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population All adult patients with long chain fatty acid oxidation disorders are under follow-up are eligible to participate in the study. Each patients will be compared to a matched healthy control subject (one healthy subject can serve as a control for more than one LcFAOD patient). Matching will be done by age (± 3 years), sex, BMI (± 2 kg/m2) and a comparable activity score assessed using a questionnaire (the Short Questionnaire to Asses Health enhancing physical activity (SQUASH).
Condition Long-chain Fatty Acid Oxidation Disorders \(LC-FAOD\)
Intervention
  • Other: Intermittent cardiopulmonary exercise test
    Exercise test with step-change from rest to a relatively low constant workload.
  • Other: Incremental cardiopulmonary exercise test
    Exercise test with incremental workload until maximal workload.
  • Other: Echography of upper leg
    Determine upper leg muscle size
  • Other: Hand grip strength with hand dynamometer
    Determine muscle strength
  • Other: Fill in questionnaires regarding physical activity
    SQUASH, mMRC, questionnaire designed to report myopathic symptoms in LcFAOD patients.
Study Groups/Cohorts
  • LcFAOD-patients
    Patients with long-chain Fatty Acid Oxidation including CPT2-, CACT-, VLCAD-, LCHAD-, or MTP-deficiency
    Interventions:
    • Other: Intermittent cardiopulmonary exercise test
    • Other: Incremental cardiopulmonary exercise test
    • Other: Echography of upper leg
    • Other: Hand grip strength with hand dynamometer
    • Other: Fill in questionnaires regarding physical activity
  • Healthy controls
    Controls are matched based on Age, Sex, BMI and comparable activity score assessed using the SQUASH questionnaire
    Interventions:
    • Other: Intermittent cardiopulmonary exercise test
    • Other: Incremental cardiopulmonary exercise test
    • Other: Echography of upper leg
    • Other: Hand grip strength with hand dynamometer
    • Other: Fill in questionnaires regarding physical activity
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Not yet recruiting
Estimated Enrollment
 (submitted: June 21, 2023)
50
Original Estimated Enrollment Same as current
Estimated Study Completion Date August 1, 2028
Estimated Primary Completion Date August 1, 2028   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • LC-FAOD patients:
  • Men and women (age ≥18 years) with a confirmed diagnosis of carnitine palmitoyltransferase 2 (CPT2) deficiency, Carnitine-acylcarnitine translocase (CACT) deficiency, Mitochondrial Trifunctional protein (MTP) deficiency, Very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency or Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency.

Healthy control subjects:

- Healthy men and women age ≥ 18 years

Exclusion Criteria:

LcFAOD patients:

  • Pregnancy
  • Recent acute myocardial infarction (<6 months prior to inclusion)
  • Uncontrolled arrhythmia/severe conduction disorder 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, anemia, severe renal dysfunction (estimated Glomerular filtration rate < 30 ml/min/1,73m2), or other chronic disease likely to significantly impact exercise performance
  • History of severe asthma or chronic obstructive pulmonary disease
  • Active use of medication likely to affect exercise tolerance

Healthy controls:

  • All abovementioned exclusion criteria for LcFOAD patients
  • History of smoking - History of asthma, chronic obstructive pulmonary disease, heart failure, heart surgery, heart rhythm disorders or congenital heart diseases
  • Chronic illness (including orthopedic, endocrinological, hematological, 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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Khya Snelder, BSc 20 5666791 ext +31 c.k.snelder@amsterdamumc.nl
Listed Location Countries Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number NCT05924555
Other Study ID Numbers NL83869.018.23
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Current Responsible Party Dr. Mirjam Langeveld, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Original Responsible Party Same as current
Current Study Sponsor Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Original Study Sponsor Same as current
Collaborators Stichting Stofwisselkracht
Investigators
Principal Investigator: Mirjam Langeveld, MD PhD Amsterdam UMC, location AMC
PRS Account Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Verification Date June 2023