Trial record 11 of 38 for:    Niemann-Pick Disease

Biomarker for Niemann Pick Type C Disease (BioNPC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01306604
Recruitment Status : Terminated (the Albrecht Kossel Institute of University Rostock terminated participation in the study conduct; Study Sponsorship is moved to Centogene AG)
First Posted : March 2, 2011
Last Update Posted : July 2, 2018
Centogene AG Rostock
Information provided by (Responsible Party):
Prof. Dr. Arndt Rolfs, University of Rostock

Brief Summary:

Niemann Pick Syndrome Type C is a lysosomal storage disorder, caused by a pathological overload of cells with unesterified cholesterol as a result of impaired lipid transport into the cell, has still the problem of the difficulties of a simple and reliable analysis for the primary diagnosis but also for the follow-up of the disease. Therefore the primary aim of our project called "BioNPC" is the development of a new plasma biomarker for the early and sensitive diagnosis of the disease. The secondary aim is the testing for clinical robustness, specificity and long-term stability of the biomarker.

Within the scope of the study the investigators would like to collect in the next 12 months from about 80 patient's plasma and parallel a simple documentation of the clinical data.

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 fillipin 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-spectometry 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. The development of new biochemical markers from the plasma of the affected patients is the goal of the study.

Study Type : Observational
Actual Enrollment : 80 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Biomarker for Niemann Pick Type C Disease an International, Multicenter, Epidemiological Study
Study Start Date : March 2011
Actual Primary Completion Date : June 2018
Actual Study Completion Date : June 2018

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 plasma and saliva [ Time Frame: 24 month ]

Secondary Outcome Measures :
  1. Testing for clinical robustness, specificity and long-term stability of the biomarker [ Time Frame: 24 month ]

Biospecimen Retention:   Samples With DNA
For the development of the new biomarkers using the technique of Mass-spectometry 20ml EDTA and a dry blood spot filter card. To proof the correct NPC nosis 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 are done in the Albrecht-Kossel-Institute for Neuroregeneration (AKos) Gehlsheimerstr.20, 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 a diagnosis of Niemann Pick Type C syndrome NPC1/NPC2 or profound suspicion for Niemann Pick Type C syndrome NPC1/NPC2 disease

Inclusion Criteria:

  • Written informed consent will be obtained from the patient or their parents before any study related procedures
  • Patients from the first day of life
  • The patient has a diagnosis of Niemann Pick Type C syndrome NPC1/NPC2 or profound suspicion for Niemann Pick Type C syndrome NPC1/NPC2 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 written informed consent will be obtained from the patient or their 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 identifier (NCT number): NCT01306604

Pediatric practice
Oran, Algeria, 31000
Juan Fernandez Hospital, Department of Neurology
Buenos Aires, Argentina, Cerviño 3356
Health Technology Assessment in Clinical Genetics Research Group
Porto Alegre -RS, Brazil, 90035-003
Hospital de Clinicas de Porto Alegre-Servico de Genetica Medica
Porto Alegre, Brazil, 90035-903
Clinics Hospital of Ribeirao Preto- University of Sao Paulo
Sao Paulo, Brazil, 14048-900
University Pediatric Hospital of Sofia
Sofia, Bulgaria, 1606
National University Hosoital Rigshospitalet, Endokrinologisk ward
Copenhagen, Denmark, 2100
Albrecht-Kossel-Institute for Neuroregeneration (AKos) Centre for Mental Health Disease University of Rostock
Rostock, Germany, 18147
Aristotle University of Thessaloniki-Ippokration General Hospital
Thessaloniki, Greece, 54642
NIRMAN, University of Mumbai
Mumbai, India, 400705
Iran, Islamic Republic of
Research center University of Welfare Science, Medical Genetics Department Sarem Women Hospital
Teheran, Iran, Islamic Republic of, 13969
Division of Child Neurology
Rome, Italy, 00188
The Children´s Memorial Istitute Poland - Department of Metabolic Disease
Warsaw, Poland
Saudi Arabia
Dhahran Health Center - Saudi Aramco Medical Services Organization
Dhahran, Saudi Arabia, 31311
Mother and Child Health Institute of Serbia - Dr. Vukan Cupic
Novi Beograd, Serbia, 11070
Sponsors and Collaborators
University of Rostock
Centogene AG Rostock
Principal Investigator: Arndt Rolfs, MD University of Rostock, Albrecht-Kossel-Institute for Neuroregeneration

Additional Information:
Responsible Party: Prof. Dr. Arndt Rolfs, Prof. Dr. med., University of Rostock Identifier: NCT01306604     History of Changes
Other Study ID Numbers: BN04/2011
First Posted: March 2, 2011    Key Record Dates
Last Update Posted: July 2, 2018
Last Verified: June 2018

Keywords provided by Prof. Dr. Arndt Rolfs, University of Rostock:
Genetic Diseases
Lipid Metabolism
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders

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