Exercise Intolerance Study in Long Chain Fatty Acid Oxidation Disorders

NCT05924555 | Recruiting

• 1 other identifier: NL83869.018.23
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Long-chain Fatty Acid Oxidation Disorders

Keywords

Long-chain Fatty Acid Oxidation disorders; Exercise intolerance; Cardiopulmonary exercise test

Outcome Measures

Primary Outcomes (8)

• 1. Differences in V'O2/ V'CO2/heart rate kinetics during the intermittent exercise test between LcFAOD patients and healthy control subjects

  At rest (baseline) and during the intermittent CPX test (30 min)

• 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).

• 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

  Baseline

Study Arms (2)

LcFAOD-patients

Patients with long-chain Fatty Acid Oxidation including CPT2-, CACT-, VLCAD-, LCHAD-, or MTP-deficiency

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

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

Interventions

Intermittent cardiopulmonary exercise test OTHER

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

Healthy controls; LcFAOD-patients

Incremental cardiopulmonary exercise test OTHER

Exercise test with incremental workload until maximal workload.

Healthy controls; LcFAOD-patients

Echography of upper leg OTHER

Determine upper leg muscle size

Healthy controls; LcFAOD-patients

Hand grip strength with hand dynamometer OTHER

Determine muscle strength

Healthy controls; LcFAOD-patients

Fill in questionnaires regarding physical activity OTHER

SQUASH, mMRC, questionnaire designed to report myopathic symptoms in LcFAOD patients.

Healthy controls; LcFAOD-patients

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

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).

You may qualify if:

• 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

You may not qualify if:

• LcFAOD patients:
• Pregnancy
• 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:
• 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

Sponsors & Collaborators

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

Study Sites (1)

Amsterdam UMC, location AMC

Amsterdam, North Holland, 1105 AZ, Netherlands

RECRUITING

MeSH Terms

Interventions

Hand Strength

Intervention Hierarchy (Ancestors)

Muscle Strength; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Mirjam Langeveld, MD PhD

  Amsterdam UMC, location AMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Khya Snelder, BSc

CONTACT

20 5666791; c.k.snelder@amsterdamumc.nl

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 21, 2023
• First Posted: June 29, 2023
• Study Start: August 1, 2023
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: August 23, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)