Assessment of the Prevalence of TTR Amyloid Neuropathy in a Population of Patients With Neuropathy of Unknown Aetiology (PRE-TRANS)

Familial amyloid neuropathy due to transthyretin gene mutations (TTR-FAP) is a rare autosomal dominant inherited disease resulting in the abnormal multi-system deposition of amyloid proteins. These deposits produce a multi-organ disease. AP is usually fatal 10 to 15 years after onset of symptoms if untreated. The prevalence of the disease remains still poorly understood and usually the search for this pathology is done in a third line of investigation. So the average time to diagnosis is extremely long, from 12 to 24 month. Now that the investigators have etiological treatment ( famidis (Vyndaqel®) and Diflunisal (Dolobid)) of this disease, it is essential to be able to detect FAP patients as early as possible. With this study, investigator decided to test for TTR mutation all patients presented with neuropathy of unknown etiology at the first line of investigation. The goal of this study is to evaluate the prevalence of FAP-TTR among neuropathy and defined the best strategy to test this population for TTR mutations.

Study Overview

• Status: Completed
• Conditions: Transthyretin Amyloidosis; Familial Amyloid Neuropathy
• Intervention / Treatment: Genetic: blood sample

• Study Type: Interventional
• Enrollment (Actual): 400
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Angers, France, 49000
    • CHU Angers
  • Brest, France, 29609
    • CHRU Brest
  • La Roche-sur-Yon, France, 85000
    • CHD La Roche sur Yon
  • La Rochelle, France, 17019
    • CH La Rochelle
  • Le Mans, France, 72033
    • CH Le Mans
  • Nantes, France
    • CHU Nantes
  • Poitiers, France, 86021
    • CHU Poitiers
  • Quimper, France, 29107
    • CH Quimper
  • Saint-Brieuc, France, 22000
    • CH Saint Brieuc
  • Saint-Grégoire, France, 35760
    • CHP Saint-Grégoire - Cabinet de Neurologie ENMG
  • Saint-Nazaire, France, 44606
    • CH Saint Nazaire
  • Tours, France, 37044
    • CHRU Tours

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patient (male and female) aged not more than 90 years old
• Patients with neuropathy identified by EDX exam or small fibre neuropathy identified from a skin biopsy.
• Patients who have undergone the minimal assessment for neuropathy as defined by the HAS (French National Health Authority): biological analysis (fasting glucose, CBC, liver and renal functions, CRP, pituitary TSH)
• Patients belonging to the social security system
• Patient who gave written informed consent

NON-INCLUSION CRITERIA Patients under legal supervision or guardianship Patients with a confirmed documented diagnosis of the cause of neuropathy Patients with evidence of Charcot Marie Tooth neuropathy: very slowly progressive course, pes cavus.

Patients who have already been investigated for a TTR mutation Pregnant women Minors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: patients with neuropathy of unknown aetiology; from a blood sample performed at inclusion, a genetic analysis will be performed to research transthyretin mutation	Genetic: blood sample; two 5 ML EDTA tubes of blood will be collected once by patient

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
to evaluate the prevalence of TTR amyloidosis	number of patients with TTR mutation	inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To identify risk factors of carrying TTR mutations amongst those presenting with "unknown aetiology" neuropathy	comparison between patient of medical history, alcohol use, familial neuropathy history, age of first symptoms apparition, description of first symptoms	inclusion
Description of the TTR-FAP cohort	medical history, alcohol use, smoking habits, familial neuropathy history, age of first symptoms apparition, description of first symptoms	inclusion

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Collaborators: Pfizer

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 21, 2017
• Primary Completion (ACTUAL): May 23, 2022
• Study Completion (ACTUAL): May 23, 2022

Study Registration Dates

• First Submitted: June 14, 2017
• First Submitted That Met QC Criteria: June 14, 2017
• First Posted (ACTUAL): June 19, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 14, 2022
• Last Update Submitted That Met QC Criteria: July 13, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Transthyretin mutation
• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Neuromuscular Diseases; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolism, Inborn Errors; Heredodegenerative Disorders, Nervous System; Amyloidosis, Familial; Peripheral Nervous System Diseases; Amyloidosis; Amyloid Neuropathies; Amyloid Neuropathies, Familial
• Other Study ID Numbers: RC16_0427

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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