Early Diagnosis of TTR Amyloidosis by Use of Molecular Biology

NCT03373370 | Completed

• 1 other identifier: NI 16007
• Study Type: observational
• Target: 560
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

Polyneuropathy; Diagnosis; Idiopathic Progressive Neuropathy

Outcome Measures

Primary Outcomes (1)

• Rate of amyloidogenic TTR mutation

  Rate of amyloidogenic TTR mutation in progressive idiopathic polyneuropathy

  1 day

Secondary Outcomes (3)

• To identify the rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy

  1 day

• To identify the rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy :variant Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

  1 day

• To identify the rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy : upper limb onset neuropathy.

  1 day

Eligibility Criteria

• Age: 51 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Multicentric prospective population in tertiary referal center for neuromuscular diseases

You may qualify if:

• A. Adult (\>50 years old)
• Chronic Peripheral neuropathies (progressing since 12 months),
• Peripheral neuropathies documentated by ENMG.
• Chronic polyneuropathy with dysautonomia (orthostatic hypotension) without diabetes
• Atypical CIDP (situations C, D (even with high protid content on CSF) \& E as defined by the French group for study of CIDP).
• Disabling neuropathy (gait or balance disorder)
• Neuropathies with upper limb onset who underwent previously CTS surgery without success.
• SLA-like syndrome : areflexia with sensory alterations on ENMG. 6: Deterioration of SNAPs' amplitudes on NCS \> 30% in less than6 months by the same NCS laboratory Mandatory : A+B+C one of 1 to 6

You may not qualify if:

• Amyloid deposit characterized on biopsy
• Causes of chronic polyneuropathy : Diabetes mellitus, Chronic alcoholic intoxication
• CIDP responding to IVIg or corticosteroids (improvement by 1 point of ONLS).
• Neuropathy associated with monoclonal gammapathy and i) anti-MAG activity or ii) POEMS syndrome or) CANOMAD syndrome.
• Ataxic Neuropathy due to vitamine B12 deficiency
• Ataxic Neuropathy due to IgM anti-MAG,
• CANOMAD syndrome,
• Ganglionopathy by Sjögren's syndrome, or paraneoplastic syndrome with Anti- Hu Antibodies, chemotherapy induced (cis-platine, oxaliplatine).
• Positive family history of FAP or FAC
• Proven AL amyloidosis
• The new criteria after amendment New eligibility criteria from the 351st patient:
• A. Adults \> 50 years old B1. Progressive axonal polyneuropathy
• Has:
• Deterioration of EMG sensory potentials \>30% in less than 6 months by the same electrophysiology team Where -. Clinical worsening over 6 months, i.e. + 1 ONLS point, or extension of sensory disorders (subjective, objective), or reduction in walking distance, or JAMAR -10% OR B2. Atypical chronic polyradiculoneuritis (CIDP)
• with pure sensitive

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (10)

Chu Bicetre

Le Kremlin-Bicêtre, Kremlin Bicetre, 94270, France

Location

CHU Martinique

Martigues, Martinique, 97200, France

Location

CHU Saint Etienne

Saint-Etienne, Saint Etienne, France

Location

CHU Grenoble

Grenoble, 38043, France

Location

CHRU Lille

Lille, 59037, France

Location

CHU Dupuytren

Limoges, 87042, France

Location

CHU La Timone

Marseille, 13000, France

Location

Hopital guy-de-Chauliac

Montpellier, 34295, France

Location

Hôpital de La Salpetrière

Paris, 75013, France

Location

Hopital de Hautepierre

Strasbourg, 67098, France

Location

MeSH Terms

Conditions

Polyneuropathies; Disease

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• David ADAMS

  Bicetre Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2017
• First Posted: December 14, 2017
• Study Start: March 17, 2017
• Primary Completion: September 30, 2021
• Study Completion: December 10, 2021
• Last Updated: December 8, 2022

Record last verified: 2022-11

Locations

FR (10)