Screening for the Transthyretin-Related Familial Amyloidotic Polyneuropathy (TTR FAP)

Completed

• Conditions: Gastrointestinal Disorders; Polyneuropathy, Amyloid; Cardiac Failure; Orthostatic Hypotension; Neuropathic Pain

• Registration Number: NCT01705626
• Lead Sponsor: CENTOGENE GmbH Rostock

Brief Summary

An International, multicenter, epidemiological observational study investigating the prevalence of Transthyretin-Related Familial Amyloidotic Polyneuropathy (TTR-FAP) in participants with small fiber polyneuropathy of no obvious etiology.

Detailed Description

Transthyretin-related Familial Amyloid Polyneuropathy (TTR-FAP) is an autosomal dominant, progressive neurodegenerative disease, with fatal outcome occurring within ten years after onset. Familial amyloid polyneuropathy (FAP) associated with mutations in the transthyretin (TTR) gene is the most common form of genetic amyloidosis. It accounts several thousand cases worldwide, with Val30Met mutation identified in most patients and with endemic foci in Portugal, Sweden and Japan.

TTR FAP is caused by the systemic deposition of amyloidogenic variants of the transthyretin protein ((Ttr) in the extra-cellular space of tissues and result in disruption of organ function.The typical presentation of TTR-FAP is a progressive sensory-motor polyneuropathy, which usually begins with loss of thermal and pain sensation in the feet, slowly ascends up the limbs and is associated with variable autonomic disturbances and extra-neurological manifestations (especially a cardiomyopathy).

The goal of the TRAP2.1 Study is to investigate the prevalence of Transthyretin-Related Familial Amyloidotic Polyneuropathy (TTR-FAP) in a cohort of 500 subjects with small fiber polyneuropathy of no obvious etiology, based on the subject's clinical presentation.

Study Timeline

• Study First Submitted: 2012-10-09
• Study First Submitted QC: 2012-10-11
• Study First Posted: 2012-10-12
• Study Start: 2016-12
• Status Verified: 2022-05
• Primary Completion: 2022-05-27
• Study Completion: 2022-05-27
• Last Update Submitted: 2022-06-02
• Last Update Posted: 2022-06-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

• Informed consent is obtained from the participant
• The participant is aged between 18 and 85 years of age
• The participant is diagnosed with small fiber polyneuropathy of no obvious etiology
• The participant has no diagnosis of alcoholism, according to International Guidelines
• The participant has not undergone chemotherapy for carcinoma

Exclusion Criteria

• Inability to provide informed consent
• The participant is younger than 18 years or older than 85 years of age
• The etiology of the small fiber polyneuropathy is clearly determined
• The participant has a diagnosis of alcoholism, according to International Guidelines
• The participant has undergone chemotherapy for carcinoma

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Epidemiological analysis of prevalence of the TTR FAP in participants with small fiber polyneuropathy of no obvious etiology.	3 years	Dry Blood Spot (DBS) samples will be genetically validated via combination of Next-Generation Sequencing (the mutation will be confirmed by Sanger sequencing) and the Multiplex ligation-dependent probe amplification (MLPA) of TTR gene

Secondary Outcome Measures

Name	Time	Method
Establishment of a biomarker in TTR-positive cohort	3 years	Samples carrying a mutation in the TTR gene will be biochemically analyzed via liquid chromatography multiple reaction monitoring MS and compared with a merged control cohort, in order to establish TTR mutation-specific biomarker/s.

Trial Locations

Locations (11)

Klinikum Wels-Grieskirchen GmbH, Abteilung für Neurologie; 🇦🇹 Wels, Austria

University of Pécs, Department of Neurology; 🇭🇺 Pécs, Hungary

University of Szeged, Department of Neurology; 🇭🇺 Szeged, Hungary

Hospital Universitario Donostia; 🇪🇸 San Sebastián, Spain

University Hospital Skopje, Department of Neurology; 🇲🇰 Skopje, North Macedonia

Jagiellonian University Medical College, Department of Neurology; 🇵🇱 Kraków, Poland

Clinical Center Niš, Department of Neurology; 🇷🇸 Niš, Serbia

University of Belgrade, Clinical Center of Serbia, Neurology Clinic, Neuropathy Center; 🇷🇸 Belgrade, Serbia

Clinical Hospital Center Zvezdara, Department of Neurology; 🇷🇸 Belgrad, Serbia

General Hospital "Dr. Djordje Joanović"; 🇷🇸 Zrenjanin, Serbia

Hospital Infanta Leonor; 🇪🇸 Madrid, Spain