The main objective of the study is to explore the fasting tolerance in MCADD patients of two and six months of life. Second, it is aimed to compare fasting tolerance and biochemical dynamics between subsets of MCADD patients. Third, it is aimed to…
ID
Source
Brief title
Condition
- Inborn errors of metabolism
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• Symptoms and signs of perturbed glucose homeostasis;
• Signs of increasing lipolysis.
Secondary outcome
• Dynamics of physiological parameters;
• Dynamics of blood-gas-analysis;
• Dynamics of remaining targeted metabolites in plasma and urine;
• Dynamics of (untargeted) multi-omics (metabolomics, lipidomics, and
proteomics) parameters.
• (Untargeted) multi-omics (metabolomics, lipidomics, and proteomics) of
hepatocytes, derived from induced-pluripotent stem cells (iPS), established
from lymphocytes;
• (When applicable) Dynamics of CGM-data.
Background summary
MCAD deficiency (MCADD; #OMIM 201450) is the most common inborn error of
mitochondrial fatty acid oxidation. Already before the introduction of
population newborn bloodspot screening (NBS), large phenotypic heterogeneity
was observed between MCADD patients, ranging between deceased patients and
asymptomatic subjects. Most clinically ascertained patients were homozygous for
the common c.985A>G ACADM mutation. After the introduction of the disorder to
the NBS, newborns with novel ACADM-genotypes have been identified. Subjects can
be classified as either severe/classical or mild/variant MCADD patients.
Dietary management guidelines are based on expert opinion and limited
experimental data summarized in one retrospective study on fasting tolerance in
35 MCADD-patients. Interestingly, data are absent on the fasting tolerance of
MCADD patients between 0-6 months of age. These guidelines cause parental
stress, especially regarding young patients (0-6 months). Moreover, the
guidelines do not take into account the heterogeneity between patients,
including the classification between severe versus mild MCADD patients. The
investigators question whether at least a subset of the MCADD patients is
overtreated with these guidelines.
Study objective
The main objective of the study is to explore the fasting tolerance in MCADD
patients of two and six months of life. Second, it is aimed to compare fasting
tolerance and biochemical dynamics between subsets of MCADD patients. Third, it
is aimed to identify novel diagnostic and/or prognostic biomarkers or fasting
tolerance. The last objective is to elucidate the (fundamental) origin of
phenotypical differences between MCADD patients.
Study design
Longitudinal, prospective, investigator-initiated human pilot-study.
Study burden and risks
The trial is considered to be a low-risk study. The clinical research team at
the UMCG has a longstanding tradition of performing supervised controlled
clinical fasting test in patients with inborn errors of metabolism, for
diagnostic as well as research purposes. No adverse effects are expected during
fasting in otherwise healthy infants with MCADD. The study holds three moderate
burdens for participants: insertion of the indwelling IV catheter, the
discomfort of fasting for the subject and the parent(s) or guardian(s), and the
time consumption. However, subjects and their parents(s) may directly benefit
from the results of this study by reduction of stress concerning feeding, under
normal, healthy circumstances. Furthermore, the treating metabolic pediatrician
may provide an (individualized) feeding regimen based on the results of the
supervised clinical fasting tests. As this project will substantiate current
management guidelines and aims to identify new (prognostic) biomarkers, it may
further improve the outcomes of future MCADD patients and their parent(s) or
guardian(s), by reduction of (unnecessary) parental stress, treatment and
follow-up.
Hanzeplein 1
Groningen 9700 RB
NL
Hanzeplein 1
Groningen 9700 RB
NL
Listed location countries
Age
Inclusion criteria
1. Age below 6 months of life. In case of premature births, the child may be included and treated according to the corrected age.;2. Established MCADD diagnosis. The diagnosis should be confirmed by a combination of (a) NBS outcome (b) MCAD enzyme activity measured with phenylpropionyl-CoA as a substrate, ideally in lymphocytes (considered to be the golden standard) and (c) ACADM gene mutation analysis.
Exclusion criteria
Any other chronic and/or genetic condition that is deemed an exclusion criterion based on the judgement of the treating metabolic paediatrician or investigators.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT03761693 |
| CCMO | NL68011.042.19 |