Magnetic Resonance Spectroscopy (MRS)-analysis of muscle energy metabolism in medium-chain acyl-CoA dehydrogenase (MCAD) deficiency

ISRCTN ISRCTN14321657
DOI https://doi.org/10.1186/ISRCTN14321657
Secondary identifying numbers N/A
Submission date
19/12/2013
Registration date
05/03/2014
Last edited
05/03/2014
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Nutritional, Metabolic, Endocrine
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Background and study aims
Fatty acid oxidation is an important source of energy during prolonged fasting. Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common inborn error of fatty acid oxidation. Patients’ experience may vary, ranging from sudden infant death to remaining without any symptoms throughout life. The reason for this has not been fully understood. Treatment includes prevention of prolonged fasting and an emergency regimen during catabolic stress (breakdown of nutrients). Patients also have difficulty in exercising continuously. During moderate-intensity exercise, energy supply is met by fatty acid oxidation of the fat stored in muscle cells. In this study we aim to analyse the effect of MCAD deficiency on exercise tolerance.

Who can participate?
Adult patients with MCAD deficiency can participate in this study.

What does the study involve?
All patients are invited to take part in two sessions of exercise on a bicycle ergometer. Blood samples will be drawn from a thin tube that will be inserted into the vein. Participants will be asked to refrain from food intake three hours before both study sessions. A food diary will be kept for 7 days prior to session 2.

What are the possible benefits and risks of participating?
No side effects of this study are expected, as the measurements are non-invasive. You may be hesitant towards the small space in the MRI scanner, but there will be sufficient time to get acquainted with the small space. Blood samples will be taken once and are without risk.

Where is the study run from?
Session 1 takes place at the paediatric test ward at the University Medical Centre Groningen (Netherlands). Session 2 takes place at the Neuroimaging Centre (NIC), Groningen (Netherlands).

When is study starting and how long is it expected to run for?
The study started in October 2012 and ended in December 2013.

Who is funding the study?
The study is funded by RVVZ Foundation, Netherlands.

Who is the main contact?
Prof. G.P.A. Smit
g.p.a.smit@umcg.nl

Contact information

Prof G. Peter A. Smit
Scientific

Hanzeplein 1
Groningen
9700 RB
Netherlands

Study information

Study designInterventional case-control study
Primary study designInterventional
Secondary study designCase-control study
Study setting(s)Hospital
Study typeDiagnostic
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleIn vivo analysis by 1H- and 31P-MRS of the effect of moderate-intensity exercise on intramyocellular lipid content and mitochondrial function in patients with MCAD deficiency
Study objectivesPatients with MCAD deficiency are unable to oxidize sufficient intramyocellular fatty acids during exercise to meet the energy demands, resulting in intramuscular energy deficiency and muscle complaints.
Ethics approval(s)Medical Ethics Committee of the University Medical Centre Groningen, 01/10/2012, ref: METc 2012/262
Health condition(s) or problem(s) studiedMCAD deficiency
InterventionAll participants undergo the two described study sessions as follows.
Incremental test on bicycle ergometer for determination of VO2max (session 1). Exercise for 80 minutes on bicycle ergometer and MRS analyses before, during and after exercise (session 2). Exercise during MRS will be performed on an MR-compatible bicycle. Venipuncture during session 2 (four small blood samples will be drawn from a cannula that will be inserted upon venipuncture for analysis of metabolites that play a role in muscle metabolism). For matters of standardization, participants will be asked to abstain from food intake three hours before both study sessions. A food diary will be kept for 7 days prior to session 2.
Intervention typeOther
Primary outcome measureIntramyocellular lipid content is measured by means of 1H-MRS. We obtain spectra at baseline and after prolonged exercise, and have professional help for analysis of the spectra.
Secondary outcome measuresConcentrations of phosphocreatine, adenosine 5’-triphosphate, inorganic phosphate, and intracellular pH.
These are measured by 31P-MRS. We obtain spectra before, during, and after exercise, and have professional help for analysis of the spectra.
Overall study start date01/10/2012
Completion date15/12/2013

Eligibility

Participant type(s)Healthy volunteer
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants16
Key inclusion criteriaPatient group: Patients with MCAD deficiency who are over 18 years of age
Control group: Healthy volunteers over 18 years of age, matched for age and gender to the patient group
Key exclusion criteria1. Disease other than MCAD deficiency
2. Contra-indications for MR analysis (e.g. the presence of metals in the body)
Date of first enrolment01/10/2012
Date of final enrolment15/12/2013

Locations

Countries of recruitment

  • Netherlands

Study participating centre

Hanzeplein 1
Groningen
9700 RB
Netherlands

Sponsor information

University Medical Centre Groningen (Netherlands)
Hospital/treatment centre

Hanzeplein 1
Groningen
9700 RB
Netherlands

ROR logo "ROR" https://ror.org/03cv38k47

Funders

Funder type

Research organisation

RVVZ Foundation (Reserves Voormalige VrijwilligeZiekenfonds-verzekeringen) (Netherlands)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan