BioMetabol: Biomarkers for Inborn Errors of Metabolism

Sponsor
CENTOGENE GmbH Rostock (Industry)
Overall Status
Completed
CT.gov ID
NCT04098198
Collaborator
(none)
462
13
31.3
35.5
1.1

Study Details

Study Description

Brief 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

Condition or Disease Intervention/Treatment Phase

    Detailed 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.

    Study Design

    Study Type:
    Observational
    Actual Enrollment :
    462 participants
    Observational Model:
    Cohort
    Time Perspective:
    Prospective
    Official Title:
    Biomarkers for Inborn Errors of Metabolism: An International, Multicenter, Observational, Longitudinal Protocol
    Actual Study Start Date :
    Aug 1, 2019
    Actual Primary Completion Date :
    Mar 11, 2022
    Actual Study Completion Date :
    Mar 11, 2022

    Arms and Interventions

    Arm Intervention/Treatment
    Participants with an Inborn Error of Metabolism

    Participants diagnosed with an Inborn Error of Metabolism aged between 2 months to 50 years

    Outcome Measures

    Primary Outcome Measures

    1. Identification of biomarkers for Inborn Errors of Metabolism [2 years]

      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.

    Secondary Outcome Measures

    1. Exploring the clinical robustness, specificity, and long-term variability of biomarkers for Inborn Errors of Metabolism [2 years]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    2 Months to 50 Years
    Sexes Eligible for Study:
    All
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University Hospital Center Mother Teresa Tirana Albania 10001
    2 Department of Clinical Genetics, Alexandria University Children's Hospital Alexandria Egypt 21131
    3 Department of Pediatrics, Alexandria University Children's Hospital Alexandria Egypt 21131
    4 Department of Medical Genetics ,Faculty of Medicine, Ain Shams University Cairo Egypt 11566
    5 Ain Shams University Cairo Egypt
    6 Children's Hospital, Faculty of Medicine, Ain Shams University Cairo Egypt
    7 Pediatrics Departmnet, Tanta University Tanta Egypt 31527
    8 Department of Molecular and Medical Genetics , Tbilisi State Medical University Tbilisi Georgia 0177
    9 Amrita Institute of Medical Sciences Kerola India 682041
    10 Children's hospital, Vilnius University Hospital Santaros klinikos Vilnius Lithuania O8406
    11 Departmnet of Pediatric Gastroenterology and Hepatology, The Children's Hospital and Institute of Child Health Lahore Pakistan 54600
    12 Emergency Hospital for Children "Louis Turcanu" Timişoara Romania 300011
    13 Lady Ridgeway Hospital for Children Colombo Sri Lanka 00800

    Sponsors and Collaborators

    • CENTOGENE GmbH Rostock

    Investigators

    • Study Chair: Peter Bauer, Prof. Dr., Centogene GmbH

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    CENTOGENE GmbH Rostock
    ClinicalTrials.gov Identifier:
    NCT04098198
    Other Study ID Numbers:
    • BioMetabol
    First Posted:
    Sep 23, 2019
    Last Update Posted:
    Mar 24, 2022
    Last Verified:
    May 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by CENTOGENE GmbH Rostock
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Mar 24, 2022