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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01306604
Recruitment Status : Not yet recruiting
First Posted : March 2, 2011
Last Update Posted : August 28, 2018
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.

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
Estimated Study Start Date : August 25, 2018
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2021

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 ]

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, 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)


  • 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


  • 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 identifier (NCT number): NCT01306604

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

Pediatric practice Not yet recruiting
Oran, Algeria, 31000
Contact: Abdelmadjid Benmansour, MD   
Principal Investigator: Abdelmadjid Benmansour, MD         
Juan Fernandez Hospital, Department of Neurology Not yet recruiting
Buenos Aires, Argentina, Cerviño 3356
Contact: Juan Politei, MD    +54 11 480 82600   
Sub-Investigator: Juan Politei, MD         
Health Technology Assessment in Clinical Genetics Research Group Not yet recruiting
Porto Alegre, Brazil, 90035-003
Contact: Ida Vanessa Schwartz, Prof   
Principal Investigator: Ida Vanessa Schwartz, Prof.         
Hospital de Clinicas de Porto Alegre-Servico de Genetica Medica Not yet recruiting
Porto Alegre, Brazil, 90035-903
Contact: Roberto Giugliani, MD    +55 51 3316 ext 8011   
Principal Investigator: Roberto Giugliani, MD         
Clinics Hospital of Ribeirao Preto- University of Sao Paulo Not yet recruiting
Sao Paulo, Brazil, 14048-900
Contact: Charles Marques Lourenco, MD   
Principal Investigator: Charles Marques Lourenco, MD         
University Pediatric Hospital of Sofia Not yet recruiting
Sofia, Bulgaria, 1606
Contact: Radka Tincheva, MD    +359 889 811 ext 976   
Principal Investigator: Radka Tincheva, MD         
National University Hosoital Rigshospitalet, Endokrinologisk ward Not yet recruiting
Copenhagen, Denmark, 2100
Contact: Ulla Feldt Rasmussen, Prof MD    +45 35451023   
Principal Investigator: Ulla Feldt Rasmussen, Prof. MD         
Albrecht-Kossel-Institute for Neuroregeneration (AKos) Centre for Mental Health Disease University of Rostock Not yet recruiting
Rostock, Germany, 18147
Contact: Arndt Rolfs, Prof.    +49 381 494 ext 9540   
Sub-Investigator: Anne Katrin Giese, MD         
Aristotle University of Thessaloniki-Ippokration General Hospital Not yet recruiting
Thessaloniki, Greece, 54642
Contact: Dimitrios Zafeiriou, MD   
Principal Investigator: Dimitrios Zafeiriou, MD         
NIRMAN, University of Mumbai Not yet recruiting
Mumbai, India, 400705
Contact: Anil Jalan, MD   
Principal Investigator: Anil Jalan, MD         
Iran, Islamic Republic of
Research center University of Welfare Science, Medical Genetics Department Sarem Women Hospital Not yet recruiting
Teheran, Iran, Islamic Republic of, 13969
Contact: Yousef Shafeghati, MD    +98(21) 44 633 ext 283   
Principal Investigator: Yousef Shafeghati, MD         
Division of Child Neurology Not yet recruiting
Rome, Italy, 00188
Contact: Vincenzo Leuzzi, Prof.    +39644712282 ext 272925   
Sub-Investigator: Mario Mastrangelo, MD         
Sub-Investigator: Letizia Nunziata, MD         
The Children´s Memorial Istitute Poland - Department of Metabolic Disease Not yet recruiting
Warsaw, Poland
Contact: Anna Tylki-Szymanska, Prof.    +48 228 15 ext 74 90   
Principal Investigator: Anna Tylki-Szymanska, Prof.         
Saudi Arabia
Dhahran Health Center - Saudi Aramco Medical Services Organization Not yet recruiting
Dhahran, Saudi Arabia, 31311
Contact: Nouriya Al-Sannaa, MD    +9663 877 ext 8290   
Principal Investigator: Nouriya Abbas Al-Sannaa, MD         
Mother and Child Health Institute of Serbia - Dr. Vukan Cupic Not yet recruiting
Novi Beograd, Serbia, 11070
Contact: Adrijan Sarajlija, MD   
Principal Investigator: Adrijan Sarajlijan, MD         
Sponsors and Collaborators
Centogene AG Rostock
Principal Investigator: Arndt Rolfs, MD Centogene AG Rostock

Additional Information:
Responsible Party: Centogene AG Rostock Identifier: NCT01306604     History of Changes
Other Study ID Numbers: BNPC06-2018
First Posted: March 2, 2011    Key Record Dates
Last Update Posted: August 28, 2018
Last Verified: August 2018

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
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