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Trial record 10 of 15 for:    "Erdheim-Chester disease"

Biomarker for Farber Disease (BioFarber) (BioFarber)

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ClinicalTrials.gov Identifier: NCT02298634
Recruitment Status : Recruiting
First Posted : November 24, 2014
Last Update Posted : September 17, 2019
Sponsor:
Information provided by (Responsible Party):
Centogene AG Rostock

Tracking Information
First Submitted Date October 23, 2014
First Posted Date November 24, 2014
Last Update Posted Date September 17, 2019
Actual Study Start Date August 20, 2018
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: January 22, 2019)
Sequencing of the Farber disease related gene [ Time Frame: 4 weeks ]
Next-Generation Sequencing (NGS) of the ASAH1 gene will be performed. The mutation will be confirmed by Sanger sequencing.
Original Primary Outcome Measures
 (submitted: November 19, 2014)
Development of a new MS-based biomarker for the early and sensitive diagnosis of Farber disease using the technique of Mass-spectometry 10ml EDTA blood, saliva tube and a dry blood spot filter card [ Time Frame: 36 month ]
Change History Complete list of historical versions of study NCT02298634 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: January 22, 2019)
The Farber disease specific biomarker candidates finding [ Time Frame: 24 months ]
The quantitative determination of small molecules (molecular weight 150-700 kD, given as ng/μl) within a dried blood spot sample will be validated via liquid chromatography multiple reaction-monitoring mass spectrometry (LC/MRM-MS) and compared with a merged control cohort. The statistically best validated molecule will be considered as a disease specific biomarker.
Original Secondary Outcome Measures
 (submitted: November 19, 2014)
Testing for clinical robustness, specificity and long-term stability of the biomarker [ Time Frame: 36 month ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Biomarker for Farber Disease (BioFarber)
Official Title Biomarker for Farber Disease - An International, Multicenter, Epidemiological Protocol
Brief Summary Development of a new mass spectrometry-based biomarker for the early and sensitive diagnosis of Farber disease from the blood
Detailed Description

Farber disease (FD), also known as Farber's lipogranulomatosis, is an autosomal recessive lysosomal storage disease marked by a deficiency in enzyme ceramidase which causes a progressive accumulation of fatty material lipids leading to abnormalities in the joints, liver, throat, tissues and central nervous system.

FD is an extremely rare disorder, with a prevalence of less than 1/1000000. Currently only about 80 cases are reported worldwide. Disease onset is typically in early infancy but may occur later in life.

FD is caused by a mutation in the ASAH1 gene, situated on the short arm of chromosome 8. This gene codes for acid ceramidase, a lysosomal heterodimeric enzyme that hydrolyzes ceramide into sphingosine and fatty acid. To date, less than 25 distinct mutations have been identified in Farber patients, but no large deletions have yet been reported. It is inherited with an autosomal recessive pattern.

The clinical presentation of FD is characterized by the appearance of subcutaneous skin nodules, ordinarily near the joints, most often interphalangeal, wrist, elbow and ankle joints, or over points of mechanical pressure. These manifestations are very painful and lead to progressive joint stiffness, limitation of motion by contractures and finally to immobilization and deformation of joints. Also, a characteristic sign of FD is the development of a progressive hoarseness due to laryngeal involvement.

Beside these major manifestations seven phenotypes have been described which differ in severity and additional organ involvement, like the lungs, nervous system, heart and lymph nodes. Dependent on residual lysosomal ceramidase turnover, patients have a variable degree of central nervous system disease, leading to progressive neurologic deterioration. In most cases the neuronal dysfunction rather than the general physical dystrophy seems to limit the duration of FD. As well, patients with FD may die due to pulmonary disease with interstitial pneumonia.

First symptoms usually appear between the newborn period and the first birthday. Milder forms of type 3 were described with onset at 20 months of age. Clinical manifestation in type 5 of FD, dominated by neurologic deterioration, begins at 1 to 2 1/2 years of life. Patients mainly die within the first years of life, but prolonged courses in patients without severe nervous disease may also be observed.

Type 1 is the most common or classical form of this condition and is associated with the classic signs of voice, skin, and joint problems that begin a few months after birth. Developmental delay and lung disease also commonly occur. Infants born with type 1 FD usually survive only into early childhood.

Types 2 and 3 generally have less severe signs and symptoms than the other types. Affected individuals have the three classic signs and usually do not have developmental delay. Children with these types of FD typically live into mid- to late childhood.

Types 4 and 5 are associated with severe neurological problems. Type 4 usually causes life-threatening health problems beginning in infancy due to massive lipid deposits in the liver, spleen, lungs, and immune system tissues. Children with this type typically do not survive past their first year of life. Type 5 is characterized by progressive decline in brain and spinal cord (central nervous system) function, which causes paralysis of the arms and legs (quadriplegia), seizures, loss of speech, involuntary muscle jerks (myoclonus), and developmental delay. Children with type 5 FD survive into early childhood.

Types 6 and 7 are very rare, and affected individuals have other associated disorders in addition to FD.

New methods, like mass-spectrometry give a good chance to characterize specific metabolic alterations in the blood of affected patients that allow diagnosing in the future the disease earlier, with a higher sensitivity and specificity.

Therefore it is the goal of the study to identify and validate a new biochemical marker from the blood of the affected patients helping to benefit other patients by an early diagnose and thereby with an earlier treatment.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:

For the development of the new biomarkers using the technique of Mass-spectometry, a blood sample will be taken via using a dry blood spot filter card. To proof the correct Farber diagnosis in those patients where up to the enrolment in the study no genetic testing has been done, sequencing of Farber will be done.

The analyses will be done at:

Centogene AG Am Strande 7 18055 Rostock Germany

Sampling Method Probability Sample
Study Population Patients with Farber disease or high-grade suspicion for Farber disease
Condition
  • Farber's Lipogranulomatosis
  • Ceramidase Deficiency
  • Hepatomegaly
  • Splenomegaly
Intervention Not Provided
Study Groups/Cohorts Observation
Patients with Farber disease or high-grade suspicion for Farber disease
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: January 22, 2019)
1000
Original Estimated Enrollment
 (submitted: November 19, 2014)
50
Estimated Study Completion Date July 2021
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria

INCLUSION CRITERIA

  • Informed consent will be obtained from the parents before any study related procedures.
  • Patients of both gender older than 2 months
  • The patient has a diagnosis of Farber disease or a high-grade suspicion for Farber disease
  • High-grade suspicion present, if one or more inclusion criteria are valid:

    1. - Positive family anamnesis for Farber disease
    2. - Hoarse cry due to laryngeal involvement
    3. - Dysostosis multiplex
    4. - Painful swollen joints,
    5. - Arthritis
    6. - Hepatomegaly
    7. - Splenomegaly
    8. - Elevated urine ceramide levels
    9. - Histiocytic infiltration of liver, spleen, and lungs
    10. - Ceramidase deficiency

EXCLUSION CRITERIA

  • No Informed consent from the parents before any study related procedures.
  • Patients of both gender younger than 2 months
  • No diagnosis of Farber disease or no valid criteria for profound suspicion of Farber disease
Sex/Gender
Sexes Eligible for Study: All
Ages 2 Months and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Volha Skrahina, Dr +4938180113594 ext 594 volha.skrahina@centogene.com
Listed Location Countries Egypt,   Germany,   India
Removed Location Countries  
 
Administrative Information
NCT Number NCT02298634
Other Study ID Numbers BFD 06-2018
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: Undecided
Responsible Party Centogene AG Rostock
Study Sponsor Centogene AG Rostock
Collaborators Not Provided
Investigators
Principal Investigator: Arndt Rolfs, Prof. Centogene AG Rostock
PRS Account Centogene AG Rostock
Verification Date March 2019