Biomarkers for Inborn Errors of Metabolism

Biomarker Clinical Trial

— BioMetabol  

Official title:

Biomarkers for Inborn Errors of Metabolism: An International, Multicenter, Observational, Longitudinal Protocol

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04098198
• Other study ID #: BioMetabol
• Status: Completed
• Start date: August 1, 2019
• Est. completion date: March 11, 2022

Study information

• Verified date: May 2021
• Source: CENTOGENE GmbH Rostock
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

International, multicenter, observational, longitudinal study to identify or monitor Inborn Error of Metabolism disease biomarkers and to explore the clinical robustness, specificity, and long-term variability of these biomarkers

Description:

Inborn Errors of Metabolism (IEM) are a large group of congenital metabolic disorders, resulting from the absence or abnormality of an enzyme or its cofactor and leading to either accumulation or deficiency of a specific metabolite. More than 800 IEM have been described in the literature, with a widely accepted classification focusing on the main substrate which is affected.

Clinical phenotypes of IEM are broad and often non-specific, mimicking more common conditions, and the onset of symptoms can occur at any age, from fetus to adult. Peroxisomal and lysosomal storage disorders, for example, often have characteristic clinical features and permanent, progressive symptoms that are independent of triggering events (e.g. anemia, thrombocytopenia, and hepatomegaly in a child of Ashkenazi-Jewish ancestry is suggestive of Gaucher disease) 6. More common findings include hypoketotic hypoglycemia, lactic acidosis, metabolic acidosis, ketosis, hyperammonemia, or other metabolic acidosis in combination with hyperammonemia.

The goal of treatment for participants with IEM are the prevention of further accumulation of harmful substances, correction of metabolic abnormalities, and elimination of toxic metabolites. Most participants suffering for rare metabolic diseases start with very severe phenotypes and with rapid progression of the disease that often leads to irreversible damage of their organs. A quick diagnosis is necessary for urgent treatment.

Biomarkers serve as measurable indicators of normal biological or pathological processes. They are typically directly linked to genetic variants in specific genes and can predict, diagnose, monitor and assess the severity of a disease.

CENTOGENE has an outstanding experience regarding the investigation and development of biomarkers for IEM. Given the large amount of participants CENTOGENE is facing and diagnosing, it has a big repertoire of samples to use for the biomarker characterization. This led for example to the identification of Lyso-Gb1 as a novel biomarker for Gaucher disease orLyso-SM509 for Niemann-Pick Disease. The established workflows and gained knowledge for the biomarker development at CENTOGENE will enhance the search for new biomarkers of other IEM.

It is the goal of this study to identify, validate, and monitor biochemical markers from affected participants for Inborn Errors of Metabolism.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 462
• Est. completion date: March 11, 2022
• Est. primary completion date: March 11, 2022
• Gender: All
• Age group: 2 Months to 50 Years

Eligibility

Inclusion Criteria:

• Informed consent is obtained from the participant or from their parent/legal guardian, before any study related procedures

• The participant aged between 2 months old and 50 years old

• The diagnosis of an Inborn Error of Metabolism is genetically confirmed

Exclusion Criteria:

• Inability to provide informed consent

• The participant is younger than 2 months old or older than 50 years old

• The diagnosis of an Inborn Error of Metabolism (IEM) is not genetically confirmed

• Previously enrolled in the study

Related Conditions & MeSH terms

• Biomarker
• Inborn Errors of Metabolism
• Metabolism, Inborn Errors

Locations

Country	Name	City	State
Albania	University Hospital Center Mother Teresa	Tirana
Egypt	Department of Clinical Genetics, Alexandria University Children's Hospital	Alexandria
Egypt	Department of Pediatrics, Alexandria University Children's Hospital	Alexandria
Egypt	Ain Shams University	Cairo
Egypt	Children's Hospital, Faculty of Medicine, Ain Shams University	Cairo
Egypt	Department of Medical Genetics ,Faculty of Medicine, Ain Shams University	Cairo
Egypt	Pediatrics Departmnet, Tanta University	Tanta
Georgia	Department of Molecular and Medical Genetics , Tbilisi State Medical University	Tbilisi
India	Amrita Institute of Medical Sciences	Kerola
Lithuania	Children's hospital, Vilnius University Hospital Santaros klinikos	Vilnius
Pakistan	Departmnet of Pediatric Gastroenterology and Hepatology, The Children's Hospital and Institute of Child Health	Lahore
Romania	Emergency Hospital for Children "Louis Turcanu"	Timisoara
Sri Lanka	Lady Ridgeway Hospital for Children	Colombo

Sponsors (1)

Lead Sponsor	Collaborator
CENTOGENE GmbH Rostock

Countries where clinical trial is conducted

Albania,  Egypt,  Georgia,  India,  Lithuania,  Pakistan,  Romania,  Sri Lanka, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identification of biomarkers for Inborn Errors of Metabolism	All samples will be analyzed for the identification of biomarker/s via Liquid Chromatography Multiple Reaction-monitoring Mass Spectrometry (LC/MRM-MS) and compared to merged control, in order to establish the disease-specific biomarker/s. The LC/MRM-MS is performed on an ABSciex 6500 triple quadrupole mass spectrometer, coupled with a Waters Acquity UPLC.	2 years
Secondary	Exploring the clinical robustness, specificity, and long-term variability of biomarkers for Inborn Errors of Metabolism	Samples will be analyzed for the identified biomarker candidates via Liquid Chromatography Multiple Reaction-monitoring Mass Spectrometry (LC/MRM-MS) and compared to merged control, in order to establish the disease-specific biomarker/s. The LC/MRM-MS is performed on an ABSciex 6500 triple quadrupole mass spectrometer, coupled with a Waters Acquity UPLC.	2 years

External Links

•   CENTOGENE is a rare disease company focused on transforming clinical, genetic, and biochemical data into medical solutions for Patients