Biomarker for Patients With Fabry Disease (BioFabry)

Sponsor

CENTOGENE GmbH Rostock (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02778295

Collaborator

(none)

1,000

Enrollment

Locations

33.4

Anticipated Duration (Months)

333.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Development of a new mass spectrography-based biomarker for the early and sensitive diagnosis of Fabry disease from the blood

Condition or Disease	Intervention/Treatment	Phase
Angiokeratomas Chronic Kidney Disease Ocular Abnormalities Hearing Loss

Detailed Description

Fabry disease is a progressive, inherited, multisystemic lysosomal storage disease characterized by specific neurological, cutaneous, renal, cardiovascular, cochleo-vestibular and cerebrovascular manifestations.

Annual incidence is reported to be 1 in 80,000 live births but this figure may underestimate disease prevalence. When late-onset variants of the disease are considered, a prevalence of approximately 1 in 3,000 has been suggested. Fabry disease is pan-ethnic.

Fabry disease is a disorder of glycosphingolipid metabolism caused by deficient or absent lysosomal alpha-galactosidase A activity related to mutations in the GLA gene (Xq21.3-q22) encoding the alpha-galactosidase A enzyme. Deficient activity results in accumulation of globotriaosylceramide (Gb3) within lysosomes, believed to trigger a cascade of cellular events.

Fabry disease is transmitted as an X-linked trait. The existence of atypical, late-onset, variants and the availability of specific therapy complicate genetic counseling.

The clinical picture covers a wide spectrum ranging from mild cases in heterozygous females, to severe cases in classically affected hemizygous males with no residual alpha-galactosidase A activity. These patients may have all the characteristic neurological (pain), cutaneous (angiokeratoma), renal (proteinuria, kidney failure), cardiovascular (cardiomyopathy, arrhythmia), cochleo-vestibular (hearing loss and vertigo) and cerebrovascular (transient ischemic attacks, strokes) symptoms of the disease.

Female patients may have very mild to severe symptoms. Pain is a common early symptom of Fabry disease (chronic pain characterized by burning and tingling paresthesia and occasional episodic crises characterized by agonizing burning pain). Pain may resolve in adulthood.

Anhidrosis or hypohidrosis may occur causing heat and exercise intolerance. Other signs include corneal changes ("cornea verticilata"), Definitive laboratory diagnosis involves demonstration of marked enzyme deficiency in hemizygous males. Enzyme analysis may occasionally help to detect heterozygotes but is often inconclusive due to random X-chromosomal inactivation, making molecular testing (genotyping) of females mandatory.

With age, progressive damage to vital organ systems develops, possibly leading to organ failure. End-stage renal disease and life-threatening cardiovascular or cerebrovascular complications limit the life-expectancy .

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 Design

Study Type:

Observational

Anticipated Enrollment :

1000 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Biomarker for Fabry Disease: BioFabry AN INTERNATIONAL, MULTICENTER, EPIDEMIOLOGICAL PROTOCOL

Actual Study Start Date :

Aug 20, 2018

Anticipated Primary Completion Date :

Jun 1, 2021

Anticipated Study Completion Date :

Jun 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Observation Patients with Fabry disease or high-grade suspicion for Fabry disease

Outcome Measures

Primary Outcome Measures

Sequencing of the Fabry disease related gene [4 weeks]
Next-Generation Sequencing (NGS) of the GLA gene will be performed. The mutation will be confirmed by Sanger sequencing.

Secondary Outcome Measures

The Fabry disease specific biomarker candidates finding [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Months and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

INCLUSION CRITERIA:

Informed consent will be obtained from the patient or the parents before any study related procedures.
Patients of both genders older than 2 months
The patient has a diagnosis of Fabry disease or a high-grade suspicion for Fabry disease
High-grade suspicion present, if one or more inclusion criteria are valid:
Positive family anamnesis for Fabry disease
Pin and burning in the hands and feet
Angiokeratomas
Gastrointestinal problems
Heart problems
Kidney problems

EXCLUSION CRITERIA:

No Informed consent from the patient or the parents before any study related procedures.
Patients of both gender younger than 2 months
No diagnosis of Fabry disease or no valid criteria for profound suspicion of Fabry disease

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Centogene GmbH	Rostock	Germany	18055
2	NIRMAN-University of Mumbai-Institute of Research in Mental and Neurological handicap	Mumbai	India	400705
3	Lady Ridgeway Hospital for Children	Colombo 8	Sri Lanka	00800c