Screening for the Transthyretin-Related Familial Amyloidotic Polyneuropathy (TTR FAP) (TRAP2-1)

Screening for the Transthyretin-Related Familial Amyloidotic Polyneuropathy (TTR-FAP): An International, Multicenter, Epidemiological Protocol

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.

Study Overview

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

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 Type: Observational
• Enrollment (Actual): 500

Contacts and Locations

Study Locations

• Austria
  • Wels, Austria, 4600
    • Klinikum Wels-Grieskirchen GmbH, Abteilung für Neurologie
• Hungary
  • Pécs, Hungary, 7624
    • University of Pécs, Department of Neurology
  • Szeged, Hungary, 6725
    • University of Szeged, Department of Neurology
• North Macedonia
  • Skopje, North Macedonia, 1000
    • University Hospital Skopje, Department of Neurology
• Poland
  • Kraków, Poland, 31-503
    • Jagiellonian University Medical College, Department of Neurology
• Serbia
  • Belgrad, Serbia, 11000
    • Clinical Hospital Center Zvezdara, Department of Neurology
  • Belgrade, Serbia, 11000
    • University of Belgrade, Clinical Center of Serbia, Neurology Clinic, Neuropathy Center
  • Niš, Serbia, 18000
    • Clinical Center Niš, Department of Neurology
  • Zrenjanin, Serbia, 23000
    • General Hospital "Dr. Djordje Joanović"
• Spain
  • Madrid, Spain, 28031
    • Hospital Infanta Leonor
  • San Sebastián, Spain, 20700
    • Hospital Universitario Donostia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Participants diagnosed with small fiber polyneuropathy of no obvious etiology.

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Participants diagnosed with small fiber polyneuropathy no obvious etiology; Participants aged between 18 and 85 years, diagnosed with small fiber polyneuropathy of no obvious etiology, without diagnosis of alcoholism and not undergoing chemotherapy for cancer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Epidemiological analysis of prevalence of the TTR FAP in participants with small fiber polyneuropathy of no obvious etiology.	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	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Establishment of a biomarker in TTR-positive cohort	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.	3 years

Collaborators and Investigators

• Sponsor: CENTOGENE GmbH Rostock
• Investigators: Study Chair: Peter Bauer, Prof., Centogene GmgH

Publications and helpful links

Helpful Links

• Related info

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): May 27, 2022
• Study Completion (Actual): May 27, 2022

Study Registration Dates

• First Submitted: October 9, 2012
• First Submitted That Met QC Criteria: October 11, 2012
• First Posted (Estimate): October 12, 2012

Study Record Updates

• Last Update Posted (Actual): June 6, 2022
• Last Update Submitted That Met QC Criteria: June 2, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Biomarker; Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy; TTR FAP
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Proteostasis Deficiencies; Autonomic Nervous System Diseases; Primary Dysautonomias; Orthostatic Intolerance; Amyloidosis; Heart Failure; Neuralgia; Gastrointestinal Diseases; Digestive System Diseases; Hypotension; Polyneuropathies; Amyloid Neuropathies; Hypotension, Orthostatic
• Other Study ID Numbers: TRAP 08-2012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No