Biomarker for Niemann Pick Type C Disease (BioNPC)

Study Description

Go to 

Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

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 Design

Go to 

Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Groups and Cohorts

Go to 

Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Group/Cohort
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

Outcome Measures

Go to 

Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

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)

Eligibility Criteria

Go to 

Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	Child, Adult, Senior
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

Criteria

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

Contacts and Locations

Go to 

Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Arndt Rolfs, MD	+49 381 494 ext 9540	arndt.rolfs@med.uni-rostock.de
Contact: Susanne Zielke	+49 381 494 ext 4739	susanne.zielke@med.uni-rostock.de

Locations

Algeria
Pediatric practice	Recruiting
Oran, Algeria, 31000
Contact: Abdelmadjid Benmansour, MD benmansour_b@yahoo.com
Principal Investigator: Abdelmadjid Benmansour, MD
Argentina
Juan Fernandez Hospital, Department of Neurology	Recruiting
Buenos Aires, Argentina, Cerviño 3356
Contact: Juan Politei, MD +54 11 480 82600 jpolitei@hotmail.com
Sub-Investigator: Juan Politei, MD
Brazil
Health Technology Assessment in Clinical Genetics Research Group	Recruiting
Porto Alegre -RS, Brazil, 90035-003
Contact: Ida Vanessa Schwartz, Prof idadschwartz@gmail.com
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 rgiugliani@hcpa.ufrgs.br
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 charlesgenetica@gmail.com
Principal Investigator: Charles Marques Lourenco, MD
Bulgaria
University Pediatric Hospital of Sofia	Recruiting
Sofia, Bulgaria, 1606
Contact: Radka Tincheva, MD +359 889 811 ext 976 drrtincheva@hotmail.com
Principal Investigator: Radka Tincheva, MD
Denmark
National University Hosoital Rigshospitalet, Endokrinologisk ward	Recruiting
Copenhagen, Denmark, 2100
Contact: Ulla Feldt Rasmussen, Prof MD +45 35451023 ufeldt@rh.dk
Principal Investigator: Ulla Feldt Rasmussen, Prof. MD
Germany
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 arndt.rolfs@med.uni-rostock.de
Sub-Investigator: Anne Katrin Giese, MD
Greece
Aristotle University of Thessaloniki-Ippokration General Hospital	Recruiting
Thessaloniki, Greece, 54642
Contact: Dimitrios Zafeiriou, MD jeff@med.auth.gr
Principal Investigator: Dimitrios Zafeiriou, MD
India
NIRMAN, University of Mumbai	Recruiting
Mumbai, India, 400705
Contact: Anil Jalan, MD jalananil@yahoo.com
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 y_shafeghati@yahoo.com
Principal Investigator: Yousef Shafeghati, MD
Italy
Division of Child Neurology	Recruiting
Rome, Italy, 00188
Contact: Vincenzo Leuzzi, Prof. +39644712282 ext 272925 vincenzo.leuzzi@uniroma1.it
Sub-Investigator: Mario Mastrangelo, MD
Sub-Investigator: Letizia Nunziata, MD
Poland
The Children´s Memorial Istitute Poland - Department of Metabolic Disease	Recruiting
Warsaw, Poland
Contact: Anna Tylki-Szymanska, Prof. +48 228 15 ext 74 90 atylki@czd.waw.pl
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 nouriya.sannaa@aramco.com
Principal Investigator: Nouriya Abbas Al-Sannaa, MD
Serbia
Mother and Child Health Institute of Serbia - Dr. Vukan Cupic	Recruiting
Novi Beograd, Serbia, 11070
Contact: Adrijan Sarajlija, MD adrijans2004@yahoo.com
Principal Investigator: Adrijan Sarajlijan, MD

Sponsors and Collaborators

University of Rostock

Centogene AG Rostock

Investigators

Principal Investigator:	Arndt Rolfs, MD	University of Rostock, Albrecht-Kossel-Institute for Neuroregeneration

More Information

Go to 

Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Centogene is one of the leading laboratories focusing on genetic testing for rare hereditary disorders. We now offer more than 2200 routine genetic and biochemical tests. 

Responsible Party:	Prof. Dr. Arndt Rolfs, Prof. Dr. med., University of Rostock
ClinicalTrials.gov Identifier:	NCT01306604 History of Changes
Other Study ID Numbers:	BN04/2011
First Posted:	March 2, 2011
Last Update Posted:	May 4, 2017
Last Verified:	May 2017

Keywords provided by Prof. Dr. Arndt Rolfs, University of Rostock:

Genetic Diseases; Lipidoses; Lipid Metabolism	Lysosomal Storage Diseases; Metabolic Diseases; Lipid Metabolism Disorders

Additional relevant MeSH terms:

Communication 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; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Aphasia	Speech Disorders; Language Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; TDP-43 Proteinopathies; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Histiocytosis, Non-Langerhans-Cell; Histiocytosis