High Intensity Exercise in Children with MCADD

NCT ID: NCT06796530

Last Updated: 2025-01-28

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-20
• Study Completion Date: 2026-05-01

Brief Summary

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.

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).

Conditions

Medium Chain Acyl CoA Dehydrogenase Deficiency

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

study

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

Group Type: EXPERIMENTAL

Cardiopulmonary exercise test (CPET)

Intervention Type: PROCEDURE

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).

High-intensity circuit training

Intervention Type: PROCEDURE

The patients will undergo a 10-minute warm-up, followed by \~30 high intensity exercise circuit.

Interventions

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).

Intervention Type: PROCEDURE

High-intensity circuit training

The patients will undergo a 10-minute warm-up, followed by \~30 high intensity exercise circuit.

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Ghent

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Patrick Verloo, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Ghent

Locations

Ghent University Hospital

Ghent, East Flanders, Belgium

Countries

Belgium

Central Contacts

Jan Stautemas, PhD

Role: CONTACT

jan.stautemas@ugent.be

+3293328967

Patrick Calders, Professor

Role: CONTACT

patrick.calders@ugent.be

+32 9 332 69 15

Other Identifiers

ONZ-2023-0579

Identifier Type: -

Identifier Source: org_study_id