Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT01306604 |
| Other study ID # |
BNPC06-2018 |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
August 20, 2018 |
| Est. completion date |
February 28, 2021 |
Study information
| Verified date |
February 2023 |
| Source |
CENTOGENE GmbH Rostock |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Development of a new MS-based biomarker for the early and sensitive diagnosis of Niemann Pick
Type C disease from Blood (plasma)
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.
