Early Diagnosis of TTR Amyloidosis by Use of Molecular Biology (ADDITION)
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|ClinicalTrials.gov Identifier: NCT03373370|
Recruitment Status : Recruiting
First Posted : December 14, 2017
Last Update Posted : April 24, 2019
Peripheral neuropathies are diseases that affect the nervous system outside the brain and spinal cord, their prevalence is 1% in the general population, the causes are extremely varied with more than 200 identified causes; the main ones are diabetes, excessive alcohol consumption and chemotherapy. They may be sometimes disabling but generally preserve autonomy.
Transthyretin amyloidosis is a rare multisystematic hereditary disease with autosomal dominant transmission. They present usually as a peripheral neuropathies (FAP). They are due to a point mutation of the transthyretin gene (chr 18q). FAP is secondary to endoneurial amyloid deposits and are characterized by a slowly progressive sensory, motor and autonomic. FAP is the most severe hereditary polyneuropathy of the adult are irreversible and fatal within 5 to 12 years from onset.
Most frequent mutation of TTR gene is located on the second exon; but more than 100 mutations have been reported.
Prevalence of FAP is 1 per 1 million inhabitants. They have been reported until 1990s' in four endemic areas North of Portugal, Sweden, Japan and Majorca. In these areas, diagnosis is facilitated because of the stereotypical presentation : a length-dependent polyneuropathy with predominant involvement of thermal and pain sensations and autonomic dysfunction, early onset in the third decade and a predominant Met30 TTR mutation. Positive family history is frequent 85% (one of the parents is affected). Diagnosis requires detection of TTR mutation by molecular biology (blood sample) and characterization of amyloid deposit on labial salivary gland biopsy.
|Condition or disease|
|Polyneuropathy Diagnosis Idiopathic Progressive Neuropathy|
Study of the TTR gene by complete sequencing; search for amyloidogenic mutations of the TTR gene (according to the site http: // amyloidosismutations.com / mut-attr.php) in the laboratory of molecular biology of the CHU BICÊTRE (APHP) managed by Pr Anne Mantel.
Preselection of the cases to be tested among the cases of peripheral neuropathies of indetermined cause referred via the network Cornamyl of which the reference centers of the neuromuscular diseases are belonging .
Currently, FAP is a worldwide disease. Diagnosis of TTR-FAP is extremely difficult and usually delayed by 4 years in non endemic areas for many reasons :
- positive family history are lacking in 50% of cases (sporadic forms).
- incomplete ability of biopsies to characterize amyloid deposits.
- clinical presentation is varied and may mimick many types of rare peripheral neuropathies: CIDP, axonal idiopathic polyneuropathy, upper limb neuropathies, recurrent carpal tunnel syndrome after surgery, ataxic neuropathy, motor neuropathy.
Conversely to endemic areas, look for V30M mutation is not enough to exclude TTR-FAP, TTR gene sequencing is required.
With the help of the french network for FAP (Cornamyl), cases have been identified in 81/100 geographical departments, with a wide genetic heterogeneity (41 mutations reported) ; age of onset is late: 75% after 50 yo.
|Study Type :||Observational|
|Estimated Enrollment :||1000 participants|
|Official Title:||Project to Accelerate the Diagnosis of TTR Amyloidosis by Use of Molecular Biology in First Intention|
|Actual Study Start Date :||March 17, 2017|
|Estimated Primary Completion Date :||March 27, 2020|
|Estimated Study Completion Date :||December 30, 2020|
- Rate of amyloidogenic TTR mutation [ Time Frame: 1 day ]Rate of amyloidogenic TTR mutation in progressive idiopathic polyneuropathy
- To identify the rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy [ Time Frame: 1 day ]Rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy : disabling neuropathy (including ataxic).
- To identify the rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy :variant Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) [ Time Frame: 1 day ]Rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy :variant Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
- To identify the rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy : upper limb onset neuropathy. [ Time Frame: 1 day ]Rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy : upper limb onset neuropathy.
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): NCT03373370
|Contact: David ADAMS||01 45 21 27 email@example.com|
|Contact: Céline LABEYRIEfirstname.lastname@example.org|
|Le Kremlin Bicetre, Kremlin Bicetre, France, 94270|
|Contact: David ADAMS 01 45 21 27 11 email@example.com|
|Contact: Céline LABEYRIE 0145213159 firstname.lastname@example.org|
|CHU Martinique||Active, not recruiting|
|Martigues, Martinique, France, 97200|
|CHU Saint Etienne||Recruiting|
|Saint-Étienne, Saint Etienne, France|
|Contact: ANTOINE Jean-Christophe 00(33) 4 77 12 78 05 email@example.com|
|Grenoble, France, 38043|
|Contact: Emmeline Lagrange 04 76 76 61 61 firstname.lastname@example.org|
|Lille, France, 59037|
|Contact: Céline TARD 00 (33) 320445962 email@example.com|
|Limoges, France, 87042|
|Contact: Laurent MAGY 05 55 05 65 61 firstname.lastname@example.org|
|CHU La Timone||Recruiting|
|Marseille, France, 13000|
|Contact: Shahram ATTARIAN 04 91 38 65 79 email@example.com|
|Montpellier, France, 34295|
|Contact: RAUL JUNTAS MORALES 04 67 33 78 22 firstname.lastname@example.org|
|Hôpital de La Salpetrière||Recruiting|
|Paris, France, 75013|
|Contact: VIALA Karine 0142161945 email@example.com|
|Hopital de Hautepierre||Recruiting|
|Strasbourg, France, 67098|
|Contact: ANDONI ECHANIZ-LAGUNA 03 88 12 85 59 firstname.lastname@example.org|
|Principal Investigator:||David ADAMS||Bicetre Hospital|