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Biomarker for Niemann Pick Type C Disease (BioNPC)

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ClinicalTrials.gov Identifier: NCT01306604
Recruitment Status : Recruiting
First Posted : March 2, 2011
Last Update Posted : March 22, 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 Niemann Pick Type C disease from Blood (plasma)

Condition or disease
Niemann-Pick Disease Niemann-Pick Disease, Type C

Detailed Description:

Niemann-Pick disease type C (NPC) is a lipid storage disease that can present in infants, children, or adults. Neonates can present with ascites and severe liver disease from infiltration of the liver and/or respiratory failure from infiltration of the lungs. Other infants, without liver or pulmonary disease, have hypotonia and developmental delay. The classic presentation occurs in mid-to-late childhood with the insidious onset of ataxia, vertical supranuclear gaze palsy (VSGP), and dementia. Dystonia and seizures are common. Dysarthria and dysphagia eventually become disabling, making oral feeding impossible; death usually occurs in the late second or third decade from aspiration pneumonia. Adults are more likely to present with dementia or psychiatric symptoms. The diagnosis of NPC is confirmed by biochemical testing that demonstrates impaired cholesterol esterification and positive filipin staining in cultured fibroblasts. Biochemical testing for carrier status is unreliable. Most individuals with NPC have NPC1, caused by mutations in the NPC1 gene; fewer than 20 individuals have been diagnosed with NPC2, caused by mutations in the NPC2 gene. Molecular genetic testing of the NPC1 genes detects disease-causing mutations in approximately 94% of individuals with NPC. Such testing is available clinically.

NPC is inherited in an autosomal recessive manner. Each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. The phenotype (i.e., age of onset and severity of symptoms) usually runs true in families. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible when the two disease-causing mutations have been identified in the family.

Since the only accepted and easily accessible lab test, Fillipin staining of skin fibroblasts, is invasive and has a rather low sensitivity and specificity and genetic sequencing is tome-consuming and expensive there is an urgent need for the improvement of diagnostic biomarkers.

New methods, like mass-spectrometry give a good chance to characterize in the blood (plasma) of affected patents specific metabolic alterations that allow to diagnose in the future the disease earlier, with a higher sensitivity and specificity. In a pilotstudy, NPC509 has been identified as a sensitive and specific biomarker (Fig 1). The structure and pathophysiological role will have to be illucidated further; however preliminary data suggests that NPC509 is a feasible biomarker for NPC. After the verfication of NPC509 as a biomarker for NPC, quantification and validation of NPC509 in saliva will allow for an easier detection method in the future.

Though NPC is a pan-ethnic disorder, the prevalence of this autosomal-recessive disorder is elevated in countries with a higher frequency of consanguinity. Therefore, we estimate that every 400th newborn in Arabian countries may be eligible for inclusion due to high-grade suspicion of NPC, while approximately every 2000th newborn in non-Arabian countries may be eligible.

The validation of this new biochemical marker from the blood (plasma) of the affected patients is the goal of the study.


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Study Type : Observational
Estimated Enrollment : 1000 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Biomarker for Niemann Pick Type C Disease (NPC1/NPC2) an International, Multicenter, Epidemiological Study
Actual Study Start Date : August 20, 2018
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : August 2021


Group/Cohort
Observation
Patients from the first day of life with Niemann Pick Type C syndrome NPC1/NPC2 or profound suspicion for Niemann Pick Type C syndrome NPC1/NPC2 disease



Primary Outcome Measures :
  1. Development of a new MS-based biomarker for the early and sensitive diagnosis of Niemann Pick Type C disease from blood (Plasma) [ Time Frame: 24 month ]
    New methods, like mass-spectrometry give a good chance to characterize specific metabolic alterations in the blood of affected patients that allow diagnosing in the future the disease earlier, with a higher sensitivity and specificity


Secondary Outcome Measures :
  1. Testing for clinical robustness, specificity and long-term stability of the biomarker [ Time Frame: 36 months ]
    the goal of the study to identify and validate a new biochemical marker from the blood of the affected patients helping to benefit other patients by an early diagnose and thereby with an earlier treatment


Biospecimen Retention:   Samples With DNA

For the development of the new biomarkers using the technique of Mass-spectometry, a blood sample of maximal 10ml blood will be taken from the patient via using a dried blood spot filter card. To proof the correct NPC diagnosis in those patients where up to the enrollment in the study no genetic testing has been done, sequencing of NPC1 and/or NPC2 will be done. The analyses will be done at the:

Centogene AG Am Strande 7 18055 Rostock Germany



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients with Niemann Pick Disease Type C (NPC1/NPC2) or profound suspicion for Niemann Pick Disease Type C disease (NPC1/NPC2)
Criteria

INCLUSION CRITERIA:

  • Informed consent will be obtained from the patient or the parents before any study related procedures.
  • Patients of both gender from one day old
  • The patient has a diagnosis of Niemann Pick Type C disease or profound suspicion for Niemann Pick Type C disease
  • High-grade suspicion present, if one or more criteria are valid:

Positive family anamnesis for NPC1/NPC2

Splenomegaly without identifiable cause

Hepatomegaly without identifiable cause

Neurological symptoms without identifiable cause

Psychiatric symptoms without identifiable cause

EXCLUSION CRITERIA:

  • No Informed consent from the patient or the parents before any study related procedures.
  • No diagnosis of NPC1/NPC2 or no valid criteria for high-grade suspicion of NPC1/ NPC2

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): NCT01306604


Contacts
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Contact: Anton Mamin, Dr. +49 381 80113 535 Anton.Mamin@centogene.com
Contact: Volha Skrahina +49 381 80 113 594 Volha.Skrahina@centogene.com

Locations
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Egypt
Children Hospital, Faculty of Medicine, Cairo University Recruiting
Cairo, Egypt, 11511
Contact: Laila Selim, Prof.         
Germany
Centogene AG Recruiting
Rostock, Germany, 18055
Contact: Arndt Rolfs, Prof.       arndt.rolfs@centogene.com   
Contact: sanjeev Kumar       Sanjeev.Kumar@centogene.com   
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.         
Pakistan
Childrens Hospital and Institute of Child Health, Ferozepur Road Recruiting
Lahore, Pakistan, 54600
Contact: Huma Arshad Cheema, Prof.         
Contact: Nadeem Anjum, MD         
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: NCT01306604     History of Changes
Other Study ID Numbers: BNPC06-2018
First Posted: March 2, 2011    Key Record Dates
Last Update Posted: March 22, 2019
Last Verified: January 2019

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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:
Genetic Diseases
Lipidoses
Lipid Metabolism
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders

Additional relevant MeSH terms:
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Pick Disease of the Brain
Niemann-Pick Diseases
Niemann-Pick Disease, Type A
Niemann-Pick Disease, Type C
Metabolism, Inborn Errors
Lipid Metabolism, Inborn Errors
Aphasia, Primary Progressive
Frontotemporal Dementia
Frontotemporal Lobar Degeneration
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Aphasia
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms
TDP-43 Proteinopathies
Neurodegenerative Diseases
Proteostasis Deficiencies
Metabolic Diseases
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic