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Clinical Trial Details — Status: Withdrawn

Administrative data

NCT number NCT01306604
Other study ID # BNPC06-2018
Secondary ID
Status Withdrawn
Phase
First received
Last updated
Start date August 20, 2018
Est. completion date February 28, 2021

Study information

Verified date February 2023
Source CENTOGENE GmbH Rostock
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

Development of a new MS-based biomarker for the early and sensitive diagnosis of Niemann Pick Type C disease from Blood (plasma)


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.


Recruitment information / eligibility

Status Withdrawn
Enrollment 0
Est. completion date February 28, 2021
Est. primary completion date February 28, 2021
Accepts healthy volunteers No
Gender All
Age group 1 Day and older
Eligibility 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 Design


Locations

Country Name City State
Germany Centogene AG Rostock
India Amrita Institute of Medical Sciences & Research Centre Cochin Kerala
India Navi Mumbai Institute of Research In Mental And Neurological Handicap (NIRMAN) Mumbai
Sri Lanka Lady Ridgeway Hospital for Children Colombo 8

Sponsors (1)

Lead Sponsor Collaborator
CENTOGENE GmbH Rostock

Countries where clinical trial is conducted

Germany,  India,  Sri Lanka, 

Outcome

Type Measure Description Time frame Safety issue
Primary Development of a new MS-based biomarker for the early and sensitive diagnosis of Niemann Pick Type C disease from blood (Plasma) 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 24 month
Secondary Testing for clinical robustness, specificity and long-term stability of the biomarker 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 36 months
See also
  Status Clinical Trial Phase
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Completed NCT02534844 - VTS-270 to Treat Niemann-Pick Type C1 (NPC1) Disease Phase 2/Phase 3
Recruiting NCT05588167 - Establishment of Genomic and Phenotypic Database for Niemann-Pick Disease, Type C
Withdrawn NCT03687476 - Safety and Tolerability Study of VTS-270 in Pediatric Participants With Niemann-Pick Type C (NPC) Disease Phase 2
Enrolling by invitation NCT05368038 - ScreenPlus: A Comprehensive, Flexible, Multi-disorder Newborn Screening Program
Completed NCT01899950 - Longitudinal Study of Cognition With Niemann-Pick Disease, Type C N/A
Terminated NCT00668564 - Hematopoietic Stem Cell Transplantation (HCT) for Inborn Errors of Metabolism Phase 2
Active, not recruiting NCT05163288 - A Pivotal Study of N-Acetyl-L-Leucine on Niemann-Pick Disease Type C Phase 3
Active, not recruiting NCT02612129 - Arimoclomol Prospective Study in Participants Diagnosed With Niemann-Pick Disease Type C Phase 2/Phase 3
Recruiting NCT03471143 - Study of IV VTS-270 for Infantile Liver Disease Associated With Niemann-Pick Disease, Type C Phase 1/Phase 2
Terminated NCT04958642 - Adrabetadex to Treat Niemann-Pick Type C1 (NPC1) Disease Phase 2/Phase 3
Terminated NCT03879655 - Open-label Study of VTS-270 in Participants With Neurologic Manifestations of Niemann-Pick Type C1 Phase 2/Phase 3
Completed NCT00975689 - Biomarker Validation for Niemann-Pick Disease, Type C: Safety and Efficacy of N-Acetyl Cysteine Phase 1/Phase 2
Recruiting NCT00344331 - Evaluation of Biochemical Markers and Clinical Investigation of Niemann-Pick Disease, Type C
Active, not recruiting NCT05758922 - Phase 2 Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral AZ-3102 in Patients With GM2 Gangliosidosis or Niemann-Pick Type C Disease Phase 2
Completed NCT03910621 - Safety and Efficacy of Miglustat in Chinese NPC Patients Phase 4
Available NCT04316637 - Early Access Program With Arimoclomol in US Patients With NPC