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Induced Pluripotent Stem Cells for Niemann Pick Disease (IPSNPABC)

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: NCT03883750
Recruitment Status : Recruiting
First Posted : March 21, 2019
Last Update Posted : April 25, 2019
Information provided by (Responsible Party):
Centogene AG Rostock

Brief Summary:
Establishment of individualized human cellular disease models based on induced pluripotent stem cells that reflect the broad heterogeneous phenotypic spectrum of Niemann Pick disease

Condition or disease
Niemann-Pick Diseases

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, 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. 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.

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, the goal of the study to prepare a cell culture from patients affected with Niemann Pick disease in order to identify novel pathways and proteins involved in disease progression that allow for an earlier diagnosis (i.e. before symptom onset) and that are suitable targets for an individualized therapeutic approach able to address not only the hepatic form, but also the neurologic form of the disease, which is less responsive to the current therapeutic approaches.

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Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Induced Pluripotent Stem Cells for the Development of Novel Drug Therapies for Hepatic and Neurological Niemann Pick Disease
Actual Study Start Date : June 19, 2018
Estimated Primary Completion Date : June 19, 2020
Estimated Study Completion Date : June 19, 2020

Primary Outcome Measures :
  1. To generate patient-specific induced pluripotent stem cells and then differentiate them into neural cells [ Time Frame: 24 months ]
    The aim of this study is to generate patient-specific induced pluripotent stem cells and then differentiate them into neural cells to study the misfolded proteins in endoplasmic reticulum, their role in untranslated protein response, and possible mechanisms to shuttle the misfolded proteins into lysosomes.

Biospecimen Retention:   Samples With DNA
The skin biopsy will be carried out for patients with a diagnosis of Niemann Pick. The biopsy is performed by the physician by means of punch biopsy (diameter 2-3 mm) under local anesthesia, preferably on the forearm (alternatively: thigh). The biopsy is immediately transferred to sterile cell culture medium and sent by center representative for the quickest possible processing to CENTOGENE's laboratory located in Germany or to professional collaborators being part of the project.

Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
The patient has a diagnosis of Niemann Pick disease

Inclusion Criteria:

  • Informed consent will be obtained from the patient or the parents before any study related procedures
  • Patients of both genders older than 6 months and younger than 80 years
  • The patient has a diagnosis of Niemann Pick disease

Exclusion Criteria:

  • No Informed consent from the patient or the parents before any study related procedures
  • Patients of both genders younger than 6 months or older than 80 years
  • No diagnosis of Niemann Pick disease

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): NCT03883750

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Contact: Volha Skrahina, Dr +4938180113594 ext 594

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Childrens Hospital and Institute of Child Health, Ferozepur Road Recruiting
Lahore, Pakistan, 54600
Contact: Huma Arshad Cheema, Prof.         
Contact: Nadeem Anjum, MD         
Sponsors and Collaborators
Centogene AG Rostock
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Study Director: Arndt Rolfs, Prof. Centogene AG Rostock

Additional Information:
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Responsible Party: Centogene AG Rostock Identifier: NCT03883750     History of Changes
Other Study ID Numbers: IPSNPABC 6-2018
First Posted: March 21, 2019    Key Record Dates
Last Update Posted: April 25, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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
Language 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