High Intensity Exercise in Children With MCADD (MCADD-EX)

Medium-Chain Acyl-Coa Dehydrogenase Deficiency (MCADD) and Exercise

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a rare genetic disorder affecting the body's ability to break down certain fats (β-oxidation) for energy, leading to symptoms like hypoketotic hypoglycaemia, jaundice, cardiomyopathy and seizures. responsible for the dehydrogenation step of fatty acids with chain lengths between 6 and 12 carbons as they undergo beta-oxidation in the mitochondria. Deficiency in MCAD can result in energy deficiency, the accumulation of acylcarnitine's and low serum carnitine concentrations.

The primary objective of the pilot study is to analyse the effects of high-intensity exercise (cardiopulmonary exercise testing (CPET) & high intensity circuit exercises ) on metabolic parameters and safety. This research is a pilot study comparing four patients with MCADD to four control subjects with the same characteristics. Blood samples are collected for analysis of substrate utilization.

Study Overview

• Status: Completed
• Conditions: Medium Chain Acyl CoA Dehydrogenase Deficiency
• Intervention / Treatment: Procedure: Cardiopulmonary exercise test (CPET); Procedure: High-intensity circuit training

Detailed Description

The primary objective of the study is to analyse the effects of high-intensity exercise (CPET & high intensity circuit exercises) on metabolic parameters and safety. Since exercise is tested approximately two hours after a meal, we expect few symptoms, as fat metabolism is only minimally engaged at this intensity. Of interest could be the recovery from exercise, as fat metabolism is presumably activated during this phase.

Each MCADD-patient will attend two experimental visits. On the day of the first visit, the patient will arrive at UZ Gent after 1.5-hours following the meal. After 30 minutes, they will perform a cardiopulmonary exercise test (CPET) on a cycle ergometer. The standard CPET protocol that will be used is as follows: first, three minutes of cycling at a constant load (body weight (kg) / 2) in Watts), followed by a maximal exercise test (Ramp protocol: (body weight (kg) / 4) in Watts per minute). During the cycling test, gas exchange (spirometry) is measured, and an ECG is taken. If no symptoms are observed, the patient may return home. On the second test day, two hours before the test, a breakfast will be consumed. 1.5-hours following the meal, the patient will arrive at UZ Gent, where a heart monitor will be placed, and an intravenous line will be inserted. Following this, the patient will undergo a high-intensity exercise circuit. Blood samples will be taken before and after the exercise at various intervals: immediately, after 30 minutes, 1 hour, and 1.5-hours. Also, RER will be determined at each timepoint using indirect calorimetry. If no symptoms appear, the patient may return home. The patient will report symptoms for the 48 hours following the test. In the blood samples, measures of substrate utilization will be monitored: Glucose, lactate, acylcarnitine levels, free fatty acids (FFA). Also a marker of muscle damage will be assessed (creatine kinase). Additional measures include: anthropometric measurements, including weight and height, physical activity through the children physical activity questionnaire).

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • East Flanders
    • Ghent, East Flanders, Belgium, 9000
      • Ghent University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 8-17y old
• Control subjects matched by sex, age, and self reported Tanner stage.
• All children: height and weight between P5-P95

Exclusion Criteria:

• No daily medication use
• No conditions other than MCADD that restrict sports participation or physiology (e.g., no heart diseases, diabetes).
• < P5 or > P95 on the height-weight curve
• No neuromotor developmental delay (e.g., delayed achievement of motor milestones)
• No recent immobilization (<6 months)
• No surgeries involving the musculoskeletal system

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: study; children aged 8-17 with Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD) or control will undergo CPET and high intensity exercise circuit.

Procedure: Cardiopulmonary exercise test (CPET); Participants undergo a CPET on a stationary bike, measuring gas exchange, ECG, and other parameters. The protocol includes 3 minutes of cycling at a constant load (body weight/2 in Watts), followed by a maximal effort test with an incremental load (Ramp protocol body weight (kg) / 4 in Watts per minute).; Procedure: High-intensity circuit training; The patients will undergo a 10-minute warm-up, followed by ~30 high intensity exercise circuit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
glucose	Analysis of glucose in blood samples taken before, immediately after, and at intervals (30 minutes, 1 hour, and 1.5 hours) following high-intensity exercise.	From start of exercise until 1.5 hours post-exercise.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiorespiratory response during CPET	Measurement of maximal oxygen uptake during the cardiopulmonary exercise test (CPET) on a stationary bike.	During CPET (approximately 30 minutes).
Safety: Incidence of adverse events during and after exercise.	Monitoring and recording of any symptoms, adverse events, or complications during exercise and the following 48 hours	During and up to 48 hours post-exercise.
acylcarnitines	Monitoring of acylcarnitines before and after high intensity exercise	From the end of the exercise circuit until 1.5 hours post-exercise.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
creatine kinase	Assessment of serum creatine kinase (CK) levels before and after exercise	From the end of the exercise circuit until 1.5 hours post-exercise.
lactate	Assessment of lactate levels before and after exercise	From the end of the exercise circuit until 1.5 hours post-exercise.
Fat metabolism during recovery phase.	Monitoring of substrate utilization (including fat metabolism) through measurement of RER.	From the end of the exercise circuit until 1.5 hours post high intensity exercise.

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Investigators: Principal Investigator: Patrick Verloo, MD, University Hospital, Ghent

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2025
• Primary Completion (Actual): March 19, 2026
• Study Completion (Actual): March 19, 2026

Study Registration Dates

• First Submitted: January 9, 2025
• First Submitted That Met QC Criteria: January 27, 2025
• First Posted (Actual): January 28, 2025

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: CPET; MCADD; high intensity exercise; acylcarnitine
• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Lipid Metabolism Disorders; Medium chain acyl CoA dehydrogenase deficiency; Investigative Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Respiratory System; Diagnostic Techniques, Cardiovascular; Heart Function Tests; Respiratory Function Tests; Ergometry; Exercise Test
• Other Study ID Numbers: ONZ-2023-0579

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All anonymous data will be made available upon publication

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No