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 : Recruiting
First Posted : March 2, 2011
Last Update Posted : May 21, 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
Estimated 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
Estimated Primary Completion Date : September 2018
Estimated Study Completion Date : October 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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

Contact: Arndt Rolfs, MD +49 381 494 ext 9540
Contact: Susanne Zielke +49 381 494 ext 4739

Pediatric practice Recruiting
Oran, Algeria, 31000
Contact: Abdelmadjid Benmansour, MD   
Principal Investigator: Abdelmadjid Benmansour, MD         
Juan Fernandez Hospital, Department of Neurology 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 Recruiting
Porto Alegre -RS, Brazil, 90035-003
Contact: Ida Vanessa Schwartz, Prof   
Principal Investigator: Ida Vanessa Schwartz, Prof.         
Hospital de Clinicas de Porto Alegre-Servico de Genetica Medica 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 Recruiting
Sao Paulo, Brazil, 14048-900
Contact: Charles Marques Lourenco, MD   
Principal Investigator: Charles Marques Lourenco, MD         
University Pediatric Hospital of Sofia Recruiting
Sofia, Bulgaria, 1606
Contact: Radka Tincheva, MD    +359 889 811 ext 976   
Principal Investigator: Radka Tincheva, MD         
National University Hosoital Rigshospitalet, Endokrinologisk ward 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 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 Recruiting
Thessaloniki, Greece, 54642
Contact: Dimitrios Zafeiriou, MD   
Principal Investigator: Dimitrios Zafeiriou, MD         
NIRMAN, University of Mumbai 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 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 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 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 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 Recruiting
Novi Beograd, Serbia, 11070
Contact: Adrijan Sarajlija, MD   
Principal Investigator: Adrijan Sarajlijan, MD         
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: May 21, 2018
Last Verified: May 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:
Language Disorders
Pick Disease of the Brain
Aphasia, Primary Progressive
Frontotemporal Dementia
Niemann-Pick Diseases
Niemann-Pick Disease, Type A
Niemann-Pick Disease, Type C
Frontotemporal Lobar Degeneration
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Speech Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms
TDP-43 Proteinopathies
Neurodegenerative Diseases
Proteostasis Deficiencies
Metabolic Diseases
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Histiocytosis, Non-Langerhans-Cell