Expanding the Biomarkers in Familial Amyloid Neuropathy: MRI and Motor Unit Estimation by Electrophysiological Study

NCT03588468 | Completed

• 1 other identifier: 2017-37
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Familial amyloid neuropathies (FAP) are hereditary disease due to a mutation of the tranthyretin gene (TTR). These neuropathies are severe and life frightening. Asymptomatic carrier of TTR mutation are now detected in large TTR-FAP family. However, it is very hard to detect the moment where a TTR mutation carrier become symptomatic: too early diagnosis exposes the patients to side effect of the treatment and too late diagnosis exposes the patient to disease progression and clinical sequels. Neurological monitoring comprises clinical examination, electrophysiology and imaging. Sensitivity and specificity of these tools are not sufficient and we have to develop new biomarkers sensitive enough to detect modifications under treatment and the moment where a TTR mutation carrier become symptomatic Magnetic resonance imaging (MRI) can well evaluate neuromuscular diseases. Electrophysiological examination is also a good tool to evaluate NAF. MUNIX is a technique that permits to estimate the number of motor unit in one muscl. MUNIX is related to the disability in chronic inflammatory neuropathies and could be more sensitive than clinical scales and other electrophysiological data to detect modification of the disease in TTR-FAP. The objective of this exploratory study is to test the applicability of MUNIX and MRI as early measures for detecting the transition from asymptomatic to symptomatic TTR-FAP. In symptomatic TTR-FAP we will determine if MUNIX and MRI data are related to clinical deficiency and disability of the patients. This is a transversal exploratory study. If we manage to demonstrate that MRI and MUNIX can segregate symptomatic versus asymptomatic TTR mutation gene carriers, we will propose a longitudinal study with a follow up of more asymptomatic gene carriers.

Conditions

Amyloid Neuropathies; Transthyretin Amyloidosis

Outcome Measures

Primary Outcomes (2)

• MRI neurography

  surface and diameter of the sciatic nerve will be measured on the T1-weighted sequence. Quantitative analyses will be performed using T2 and MTR sequences on the sciatic nerve at the middle of the thigh.

  1 hour

• MUNIX

  Supramaximal distal stimulations of the corresponding nerves will be performed to achieve maximal CMAP amplitude with minimum rise time and sharp negative take-off.

  30 minutes

Study Arms (3)

healthy

SHAM COMPARATOR

will be defined as persons without pathological mutation of the TTR gene Electrophysiological biomarkers and MRI biomarkers will be performed

Other: Electrophysiological biomarkers; Other: MRI biomarkers

Asymptomatic carriers

ACTIVE COMPARATOR

will be defined as persons with a known pathological mutation of the TTR gene but with no clinical complain, normal clinical examination, and normal renal and cardiac investigations. Electrophysiological biomarkers and MRI biomarkers will be performed

Other: Electrophysiological biomarkers; Other: MRI biomarkers

Symptomatic carriers

EXPERIMENTAL

will be defined as persons with a known pathological mutation of the TTR gene with clinical complain, abnormal clinical examination, and abnormal renal and cardiac investigations. Electrophysiological biomarkers and MRI biomarkers will be performed

Other: Electrophysiological biomarkers; Other: MRI biomarkers

Interventions

Electrophysiological biomarkers OTHER

Motor and sensory nerve conduction study will be performed on median, ulnar, tibialis, peroneal and sural nerves.

Asymptomatic carriers; Symptomatic carriers; healthy

MRI biomarkers OTHER

T1, T2, STIR and magnetisation transfer ratio (MTR) will be performed unilaterally on the thigh and the leg.

Asymptomatic carriers; Symptomatic carriers; healthy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Subject must meet the following criteria to be included:
• years and older
• Men or women
• Carrying TTR mutation
• Having social insurance
• Given written informed consent after being informed of the purpose and potential risks
• Subjects with the following criteria will be excluded:
• Subject with a contraindication for MRI explorations
• Subject unable to understand the purpose and conditions of carrying out the study, unable to give consent
• Subject must meet the following criteria to be included:
• years and older
• Men or women
• Having social insurance
• Given written informed consent after being informed of the purpose and potential risks
• Subjects with the following criteria will be excluded:

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead

Study Sites (1)

Assistance Publique Des Hopitaux de Marseille

Marseille, PACA, 13354, France

Location

MeSH Terms

Conditions

Amyloid Neuropathies; Amyloidosis, Hereditary, Transthyretin-Related

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• EMILIE GARRIDO PRADALIE

  APHM

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 4, 2018
• First Posted: July 17, 2018
• Study Start: September 20, 2018
• Primary Completion: December 18, 2019
• Study Completion: December 18, 2019
• Last Updated: October 4, 2022

Record last verified: 2022-10

Locations

FR (1)