- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01306604
Biomarker for Niemann Pick Type C Disease (BioNPC) (BioNPC)
Biomarker for Niemann Pick Type C Disease (NPC1/NPC2) an International, Multicenter, Epidemiological Study
Study Overview
Status
Conditions
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.
Study Type
Contacts and Locations
Study Locations
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Rostock, Germany, 18055
- Centogene AG
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Mumbai, India, 400705
- Navi Mumbai Institute of Research In Mental And Neurological Handicap (NIRMAN)
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Kerala
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Cochin, Kerala, India, 682041
- Amrita Institute Of Medical Sciences & Research Centre
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Colombo 8, Sri Lanka, 00800c
- Lady Ridgeway Hospital for Children
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
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
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
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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
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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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
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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
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24 month
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Testing for clinical robustness, specificity and long-term stability of the biomarker
Time Frame: 36 months
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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
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36 months
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Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Metabolic Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Lymphatic Diseases
- Neurologic Manifestations
- Neurobehavioral Manifestations
- Neurocognitive Disorders
- Genetic Diseases, Inborn
- Neurodegenerative Diseases
- TDP-43 Proteinopathies
- Proteostasis Deficiencies
- Metabolism, Inborn Errors
- Lysosomal Storage Diseases
- Lipid Metabolism Disorders
- Dementia
- Brain Diseases, Metabolic
- Brain Diseases, Metabolic, Inborn
- Language Disorders
- Communication Disorders
- Sphingolipidoses
- Lysosomal Storage Diseases, Nervous System
- Lipidoses
- Lipid Metabolism, Inborn Errors
- Speech Disorders
- Frontotemporal Lobar Degeneration
- Aphasia
- Histiocytosis, Non-Langerhans-Cell
- Histiocytosis
- Frontotemporal Dementia
- Aphasia, Primary Progressive
- Pick Disease of the Brain
- Niemann-Pick Diseases
- Niemann-Pick Disease, Type A
- Niemann-Pick Disease, Type C
Other Study ID Numbers
- BNPC06-2018
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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