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Biomarker for Gilbert Disease (BioGilbert) (BioGilbert)

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ClinicalTrials.gov Identifier: NCT02712138
Recruitment Status : Recruiting
First Posted : March 18, 2016
Last Update Posted : September 17, 2019
Sponsor:
Information provided by (Responsible Party):
Centogene AG Rostock

Brief Summary:
Development of a new MS-based biomarker for the early and sensitive diagnosis of Gilbert disease from blood

Condition or disease
Meulengracht Syndrome Hyperbilirubinemia Unconjugated Benign Bilirubinemia

Detailed Description:

Gilbert syndrome is a mild genetic liver disorder in which the body cannot properly process bilirubin, a yellowish waste product that is formed when old or worn out red blood cells are broken down (hemolysis). It is inherited as an autosomal recessive trait.

Individuals with Gilbert syndrome have elevated levels of bilirubin (hyperbilirubinemia), because they have a reduced level of a specific liver enzyme required for elimination of bilirubin. Most affected individuals have no symptoms or may only exhibit mild yellowing of the skin, mucous membranes, and whites of the eyes (jaundice). Jaundice may not be apparent until adolescence. Bilirubin levels may increase following stress, exertion, dehydration, alcohol consumption, fasting, and/or infection. In some individuals, jaundice may only be apparent when triggered by one of these conditions. Some affected individuals have reported vague, unspecific symptoms including fatigue, weakness and gastrointestinal symptoms such as nausea, abdominal discomfort, and diarrhea.

Gilbert syndrome is diagnosed more often in males than females. The disorder affects approximately 3-7 percent of individuals in the general population, and affects individuals of all races. It is present at birth, but may remain undiagnosed until the late teens or early twenties.

Gilbert syndrome is caused by mutations to the UGT1A1 gene located on the long arm (q) of chromosome 2 (2q37). The UGT1A1 gene contains instructions for creating (encoding) a liver enzyme known as uridine disphosphate-glucuronosyltransferase-1A1 (UGT1A1). This enzyme is required for the conversion (conjugation) and subsequent excretion of bilirubin from the body. Individuals with Gilbert syndrome retain approximately one third of the normal UGT1A1 enzyme activity and are able to conjugate enough bilirubin to prevent symptoms from developing.

Mild jaundice associated with Gilbert syndrome occurs due to reduced amounts of this enzyme, which results in the accumulation of unconjugated bilirubin in the body. Bilirubin circulates in the liquid portion of the blood (plasma) bound to a protein called albumin; this is called unconjugated bilirubin, which does not dissolve in water (water-insoluble). Normally, this unconjugated bilirubin is taken up by the liver cells and, with the help of the UGT1A1 enzyme, is converted to form water-soluble bilirubin glucuronides (conjugated bilirubin), which are then excreted in the bile. The bile is stored in the gall bladder and, when called upon, passes into the common bile duct and then into the upper portion of the small intestine (duodenum) and aids in digestion. Most bilirubin is eliminated from the body in the feces.

New methods, like mass-spectrometry give a good chance to characterize specific metabolic alterations in the blood (plasma) of affected patients that allow diagnosing in the future the disease earlier, with a higher sensitivity and specificity.

Therefore it is the goal of the study to identify and validate a new biochemical marker from the plasma of the affected patients helping to benefit other patients by an early diagnose and thereby with an earlier treatment.


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Study Type : Observational
Estimated Enrollment : 1000 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Biomarker for Gilbert Disease - An International, Multi- Center, Epidemiological Protocol
Actual Study Start Date : August 20, 2018
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2021

Resource links provided by the National Library of Medicine





Primary Outcome Measures :
  1. Sequencing of the Gilbert disease related gene [ Time Frame: 4 weeks ]
    Next-Generation Sequencing (NGS) of the UGT1A1 gene will be performed. The mutation will be confirmed by Sanger sequencing.


Secondary Outcome Measures :
  1. The Gilbert disease specific biomarker candidates finding [ Time Frame: 24 months ]
    The quantitative determination of small molecules (molecular weight 150-700 kD, given as ng/μl) within a dried blood spot sample will be validated via liquid chromatography multiple reaction-monitoring mass spectrometry (LC/MRM-MS) and compared with a merged control cohort. The statistically best validated molecule will be considered as a disease specific biomarker.


Biospecimen Retention:   Samples With DNA

Laboratory Blood Test

For the development of the new biomarkers using the technique of Mass-spectrometry 7,5 ml EDTA blood and a dry blood spot filter card are taken. To proof the correct Gilbert diagnosis in those patients where up to the enrollment in the study no genetic testing has been done, sequencing of Gilbert disease will be done.

The analyses will be done at:

Centogene AG Am Strande 7 18055 Rostock Germany



Information from the National Library of Medicine

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Ages Eligible for Study:   2 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients with Gilbert disease or high-grade suspicion for Gilbert disease
Criteria

INCLUSION CRITERIA

  • Informed consent will be obtained from the patient or the parents before any study related procedures.
  • Patients of both genders older than 2 months
  • The patient has a diagnosis of Gilbert disease or a high-grade suspicion for Gilbert disease
  • High-grade suspicion present, if one or more inclusion criteria are valid:

    1. - Positive family anamnesis for Gilbert disease
    2. - Hyperbilirubinemia
    3. - Abdominal pain
    4. - Irritable bowel syndrome
    5. - Familial nonhemolytic jaundice

EXCLUSION CRITERIA

  • No Informed consent from the patient or the parents before any study related procedures.
  • Patients of both gender younger than 2 months
  • No diagnosis of Gilbert disease or no valid criteria for profound suspicion of Gilbert disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02712138


Contacts
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Contact: Arndt Rolfs, Prof +4938180113500 ext 500 arndt.rolfs@centogene.com

Locations
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Egypt
Children Hospital, Faculty of Medicine, Cairo University Recruiting
Cairo, Egypt, 11511
Contact: Laila Selim, Prof.         
India
Amrita Institute of Medical Sciences & Research Centre Recruiting
Cochin, Kerala, India, 682041
Contact: Sheela Nampoothiri, Dr.         
Navi Mumbai Institute of Research In Mental And Neurological Handicap (NIRMAN) Recruiting
Mumbai, India, 400705
Contact: Anil Jalan, Dr.         
Sponsors and Collaborators
Centogene AG Rostock
Investigators
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Principal Investigator: Arndt Rolfs, MD Centogene AG Rostock

Additional Information:
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Responsible Party: Centogene AG Rostock
ClinicalTrials.gov Identifier: NCT02712138     History of Changes
Other Study ID Numbers: BGI 06-2018
First Posted: March 18, 2016    Key Record Dates
Last Update Posted: September 17, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Centogene AG Rostock:
Gilbert Syndrome
Biomarker
Additional relevant MeSH terms:
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Gilbert Disease
Hyperbilirubinemia
Pathologic Processes
Hyperbilirubinemia, Hereditary
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases