Clinical trial NCT03233841: Farber Disease Natural History Study
Official title: Observational and Cross-Sectional Cohort Study of the Natural History and Phenotypic Spectrum of Farber Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Farber Disease
Farber's Disease
Farber Lipogranulomatosis
Acid Ceramidase Deficiency
Ceramidase Deficiency
N-Laurylsphingosine Deacylase Deficiency
ASAH1 Mutation
Keywords: Natural History Study
Observational Study
Prospective Study
Retrospective Study
Farber Disease
Farber's Disease
ASAH1
Subcutaneous Nodules
Lysosomal Storage Disease
Lysosomal Storage Disease, Nervous System
Metabolic Diseases
Lipid Metabolism Disorders
Lipidoses
Sphingolipidoses
Genetic Disease, Inborn
Musculoskeletal Diseases
Connective Tissue Diseases
Central Nervous System Diseases
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases, Inborn
Brain Diseases
Infant, Newborn Diseases
Inborn Errors of Metabolism
Inherited Metabolic Disease
Lead sponsor: Sumitomo Pharma Switzerland GmbH
Sponsor class: INDUSTRY
First posted: 2017-07-31
Enrollment: 45
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All identified patients with Farber disease, living or deceased, diagnosed by biochemical or genetic criteria, or both, are eligible for inclusion in the study without regard to any other baseline or demographic characteristics. Both subjects who have undergone HSCT and those who have not are eligible to participate.

Brief summary: The primary objective of this study is to establish the natural history of Farber disease (acid ceramidase deficiency) through the collection and analysis of retrospective and prospective data on patients diagnosed with Farber disease. All patients diagnosed with Farber disease are eligible, including both those who have and have not undergone hematopoietic stem cell transplantation (HSCT). Additionally, data and records from deceased patients will provide valuable retrospective data for this study.

The secondary objective of the study is to establish a set of clinical data, laboratory data (biomarkers), and functional data potentially useful for:

* Assessing the efficacy of HSCT and the efficacy of potential future therapies (for example with RVT-801, recombinant human acid ceramidase) in Farber disease
* Characterizing changes in symptoms of patients over time
* Characterizing distinct groups (phenotypes) within the patient population
* Documenting the disease histories of individual patients to serve as intra-subject control data for those who may enroll in any future clinical studies with therapies for Farber disease

The exploratory objectives of the study are:

* To explore the relationship between patient disease activity or phenotype and specific ceramide levels or specific immunologic markers (cytokines/chemokines) in blood
* To evaluate a standardized tool, the Farber Disease Natural History Instrument (FDNI), to be used for the collection of patient history information, data from clinical, laboratory, genetic, and functional studies, and data from review of medical records


Eligibility criteria: Inclusion Criteria:

* Living or deceased subjects with diagnosis of Farber disease, based on clinical (typical clinical symptoms) and biochemical and/or genetic criteria, as follows:

  * Biochemical: An acid ceramidase activity value in white blood cells, cultured skin fibroblasts or other biological sources (e.g., plasma) that is less than 30% of control (normal) values established by the testing laboratory. For deceased subjects only, storage of ceramide in cells from histopathologic sections is also adequate to confirm the diagnosis.
  * Genetic: Nucleotide changes within both alleles of the acid ceramidase gene (ASAH1) or cDNA that indicate, through bioinformatics, gene expression studies, or other methods, a possible loss of function of the acid ceramidase protein.
* Informed consent or assent, for living subjects. For deceased subjects it is the responsibility of the principal investigator to ensure that the proper requirements are met according to local laws and regulations.

Exclusion Criteria:

• Current use or history of use in the past 30 days of an investigational agent (with exception of off-label use of medications).

Primary outcomes:
measure: Establish a dataset on the natural history of Farber Disease
timeFrame: Up to 21 months
Secondary outcomes:
Other outcomes:
Locations:
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital Oakland
state: California
city: Washington
country: United States
facility: Children's National Health System
state: District of Columbia
city: Córdoba
country: Argentina
facility: Hospital de Niños de la Santisima Trinidad
state: CP
city: Montreal
country: Canada
facility: Montreal Children's Hospital
state: Quebec
city: Cairo
country: Egypt
facility: Cairo University
city: Giessen
country: Germany
facility: Universitätsklinikum Giessen, Zentrum für Kinderheilkunde und Jugendmedizin
state: Hessen
city: Dehli
country: India
facility: Lok Nayak Hospital & Maulana Azad Medical College
city: Delhi
country: India
facility: Sir Ganga Ram Hospital
city: Genoa
country: Italy
facility: IRCCS Istituto Giannina Gaslini
city: Milan
country: Italy
facility: University of Milan
city: Stockholm
country: Sweden
facility: Astrid Lindgrens barnsjukhus, Karolinska University Hospital Solna
city: Adana
country: Turkey
facility: Cukurova University School of Medicine
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty Hospital
city: Istanbul
country: Turkey
facility: Istanbul University Istanbul School of Medicine
city: İzmir
country: Turkey
facility: Dokuz Eylul University School of Medicine
Study officials:
References:
citation: Elsea SH, Solyom A, Martin K, Harmatz P, Mitchell J, Lampe C, Grant C, Selim L, Mungan NO, Guelbert N, Magnusson B, Sundberg E, Puri R, Kapoor S, Arslan N, DiRocco M, Zaki M, Ozen S, Mahmoud IG, Ehlert K, Hahn A, Gokcay G, Torcoletti M, Ferreira CR. ASAH1 pathogenic variants associated with acid ceramidase deficiency: Farber disease and spinal muscular atrophy with progressive myoclonic epilepsy. Hum Mutat. 2020 Sep;41(9):1469-1487. doi: 10.1002/humu.24056. Epub 2020 Jun 24.