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

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ClinicalTrials.gov Identifier: NCT03588468
Recruitment Status : Not yet recruiting
First Posted : July 17, 2018
Last Update Posted : July 18, 2018
Sponsor:
Information provided by (Responsible Party):
Assistance Publique Hopitaux De Marseille

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.


Condition or disease Intervention/treatment Phase
Amyloid Neuropathies Transthyretin Amyloidosis Other: Electrophysiological biomarkers Other: MRI biomarkers Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Expanding the Biomarkers in Familial Amyloid Neuropathy: Magnetic Resonance Imaging (MRI) and Motor Unit Estimation by Electrophysiological Study
Estimated Study Start Date : August 2018
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : May 2020


Arm Intervention/treatment
Sham Comparator: healthy
will be defined as persons without pathological mutation of the TTR gene Electrophysiological biomarkers and MRI biomarkers will be performed
Other: Electrophysiological biomarkers
Motor and sensory nerve conduction study will be performed on median, ulnar, tibialis, peroneal and sural nerves.

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

Active Comparator: Asymptomatic carriers

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

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

Experimental: Symptomatic carriers

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

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




Primary Outcome Measures :
  1. MRI neurography [ Time Frame: 1 hour ]
    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.

  2. MUNIX [ Time Frame: 30 minutes ]
    Supramaximal distal stimulations of the corresponding nerves will be performed to achieve maximal CMAP amplitude with minimum rise time and sharp negative take-off.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

For a subject to be eligible, all of the inclusion criteria and none of the exclusion criteria must be met.

3.1.1. TTR mutation gene carriers 3.1.1.a. Inclusion criteria

Subject must meet the following criteria to be included:

  • 18 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

3.1.1.b. Exclusion criteria

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

3.1.2. Healthy controls 3.1.2.a. Inclusion criteria

Subject must meet the following criteria to be included:

  • 18 years and older
  • Men or women
  • Having social insurance
  • Given written informed consent after being informed of the purpose and potential risks

3.1.2.b. Exclusion criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03588468


Contacts
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Contact: Shahram ATTARIAN, MD +33 4 91 38 65 79 Shahram.ATTARIAN@ap-hm.fr

Locations
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France
Assistance Publique Des Hopitaux de Marseille Not yet recruiting
Marseille, Paca, France, 13354
Contact: SHAHRAM ATTARIAN, MD    +33 4 91 38 65 79    Shahram.ATTARIAN@ap-hm.fr   
Sponsors and Collaborators
Assistance Publique Hopitaux De Marseille
Investigators
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Study Director: EMILIE GARRIDO PRADALIE APHM

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Responsible Party: Assistance Publique Hopitaux De Marseille
ClinicalTrials.gov Identifier: NCT03588468     History of Changes
Other Study ID Numbers: 2017-37
First Posted: July 17, 2018    Key Record Dates
Last Update Posted: July 18, 2018
Last Verified: July 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Amyloid Neuropathies
Amyloid Neuropathies, Familial
Amyloidosis
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Proteostasis Deficiencies
Metabolic Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Amyloidosis, Familial
Metabolism, Inborn Errors