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Trial record 59 of 359 for:    transthyretin

Early and Systematic Screening in Chronic Neuropathy (TTR-FAP)

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ClinicalTrials.gov Identifier: NCT03720275
Recruitment Status : Recruiting
First Posted : October 25, 2018
Last Update Posted : December 3, 2018
Sponsor:
Collaborator:
University of Bordeaux
Information provided by (Responsible Party):
University Hospital, Bordeaux

Brief Summary:
TTR-FAP is a rare disabling inherited disorder that predominantly affects the peripheral nervous system and the heart. Due to an important phenotypic and genetic heterogeneity, the diagnosis is often delayed, preventing therefore early onset treatment. Our project is to evaluate the prevalence of TTR-FAP in a series of 130 patients with from chronic neuropathy of undetermined aetiology through a systematic screening of TTR mutations.

Condition or disease Intervention/treatment Phase
Amyloid Neuropathies, Familial Genetic: Systematic screening of TTR mutations Not Applicable

Detailed Description:

Transthyretin familial amyloid polyneuropathy (TTR-FAP) is an autosomal dominant disorder, highly disabling and life-threatening, resulting of transthyretin (TTR) gene mutation. Clinically, TTR FAP is characterized by progressive sensorimotor and dysautonomic neuropathy, usually fatal within a few years. The disease prevalence is highly variable, with a large genotypic and phenotypic heterogeneity. Early and accurate diagnosis remains essential to propose early treatment. New pharmacotherapies have been developed, such as Tafamidis®, and many patients can avoid liver transplant formerly considered as the only therapeutic option. The prevalence of TTR-FAP disease has been previously estimated in series of patients with severe and progressive neuropathy, frequently leading to a delayed diagnosis. TTR-FAP is also easily suspected when neuropathy is associated with cardiac symptoms or dysautonomia.

Currently, genetic testing of TTR-FAP is targeted and is only prescribed to patients in whom the first-line assessment recommended by the High Authority for Health (HAS) did not identify a cause, and on the basis of a worsening of symptoms. An early diagnosis in those cases would allow earlier treatment and monitoring. No data are available about the prevalence of TTR-FAP in populations of patients with from chronic neuropathy of unknown aetiology, through a systematic screening of TTR mutations.

The diagnosis of TTR-FAP will be performed using standard procedures following international recommendations, requiring genetic analysis of the TTR gene.

The patients with a diagnosis of TTR-FAP confirmed during this study will be seen for an additional visit in the Investigating Centre and proposed suitable follow up, treatment and care.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Evaluation of a New Diagnostic Approach to Familial Amyloid Neuropathy by Mutation of the TTR Gene in a Population of Idiopathic Chronic Neuropathies
Actual Study Start Date : November 27, 2018
Estimated Primary Completion Date : May 27, 2020
Estimated Study Completion Date : November 27, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: patients with chronic neuropathy of unknown aetiology
For the 130 patients with chronic neuropathy of unknown aetiology, the diagnosis of TTR-FAP will be performed using standard procedures following international recommendations, requiring genetic analysis of the TTR gene.
Genetic: Systematic screening of TTR mutations
The diagnosis of TTR-FAP requires genetic analysis using direct sequencing of TTR gene.The diagnosis of TTR-FAP will be performed using standard procedures following international recommendations, requiring genetic analysis of the TTR gene.




Primary Outcome Measures :
  1. Diagnosis of TTR-FAP [ Time Frame: Genetic analyzes will be performed every three months from the first inclusion ]
    Proportion of TTR-FAP in the 130 patients with chronic neuropathy of unknown aetiology


Secondary Outcome Measures :
  1. Age of patient at diagnosis [ Time Frame: at the inclusion visit ]
  2. History of dysautonomias [ Time Frame: at the inclusion visit ]
    History of dysautonomias at the interview

  3. Signs of dysautonomias [ Time Frame: at the inclusion visit ]
    signs of dysautonomias at the interview

  4. Weight of patient [ Time Frame: at the inclusion visit ]
    weight

  5. Height of patient [ Time Frame: at the inclusion visit ]
    height

  6. Motor deficit of the lower limbs evaluated by a subscore of the Neuropathy Impairment Scale (NIS) [ Time Frame: at the inclusion visit ]
    The Motor deficit of the lower limbs will be assessed through a sub score of the Neuropathy Impairment Scale (NIS). The maximum score on the NIS scale is 244 points. The motor sub score, including the evaluation of the upper and lower limbs, is scored on 192 points. This scale allows to obtain a quantification of the clinical examination. Each item is evaluated between 0 and 4 points.

  7. Motor deficit of the upper limbs evaluated by a subscore of the Neuropathy Impairment Scale (NIS) [ Time Frame: at the inclusion visit ]
    The Motor deficit of the upper limbs will be assessed through a sub score of the Neuropathy Impairment Scale (NIS). The maximum score on the scale is 244 points. The motor sub score, including the evaluation of the upper and lower limbs, is scored on 192 points. This scale allows to obtain a quantification of the clinical examination. Each item is evaluated between 0 and 4 points.

  8. Sensory deficit evaluated by a subscore of the Neuropathy Impairment Scale (NIS) [ Time Frame: at the inclusion visit ]
    The Sensory deficit will be assessed through a sub score of the Neuropathy Impairment Scale (NIS). The maximum score on the scale is 244 points. The sensory sub score is scored on 20 points. This scale allows to obtain a quantification of the clinical examination. Each item is evaluated between 0 and 2 points.

  9. Presence / Absence of reflexes osteo-tendinous evaluated by a subscore of the Neuropathy Impairment Scale (NIS) [ Time Frame: at the inclusion visit ]
    The Presence/Absence of reflexes osteo-tendinous will be assessed through a sub score of the Neuropathy Impairment Scale (NIS). The maximum score on the scale is 88 points. The reflexes sub score is scored on 8 points. This scale allows to obtain a quantification of the clinical examination. Each item is evaluated between 0 and 2 points.

  10. Presence of orthostatic hypotension [ Time Frame: at the inclusion visit ]
    Blood pressure measurement by the nurse

  11. Dysautonomia score [ Time Frame: at the inclusion visit ]
    Score at the clinical scale assessing autonomic dysfunction according to 5 modalities: orthostatic hypotension, high digestive motor disorders, low digestive motor disorders, vesicosphincteric disorders, erectile dysfunction

  12. Rasch-built Overall Disability Scale (RODS) score [ Time Frame: at the inclusion visit ]
    Score at the RODS, a functional scale that captures daily activity and social participation limitations in patients affected by polyneuropathy (self-questionnaire)

  13. Overall Neuropathy Limitations Scale (ONLS) score [ Time Frame: at the inclusion visit ]
    The ONLS is a validated neuropathy functional scale evaluating the performance of upper and lower cells. The upper limbs sub score is scored on 5 points and the lower limbs sub score is scored on 7 points. The scale thus ranges from 0 (no disability) to 12 points (disability maximum)

  14. Electroneuromyography findings (ENMG): axonal, demyelinating or mixed neuropathy). [ Time Frame: at the inclusion visit ]


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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients of both sexes presenting chronically (> 3 months):

    • neuropathy confirmed by an electroneuromyography
    • without obvious etiology (diabetes, alcohol consumption, renal insufficiency, neurotoxic substances intake, family history of diagnosed hereditary neuropathy)
    • without anomaly of the following biological examinations: fasting blood glucose, blood count, gamma-glutamyl transferases, average cell volume, transaminases, serum creatinine clearance, C-reactive protein, TSH
  • Aged 18 to 90 years Patients giving their free and informed consent to participate, after research information

Exclusion Criteria:

  • People placed under the protection of justice.
  • Patients who are not affiliated or who are not beneficiaries of a social security scheme
  • Patients with chronic neuropathy related to a known etiology

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): NCT03720275


Contacts
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Contact: Guilhem Solé, MD 05 57 82 13 80 guilhem.sole@chu-bordeaux.fr
Contact: Aurore Capelli, PhD 05 57 82 08 77 aurore.capelli@chu-bordeaux.fr

Locations
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France
Reference center for neuromuscular diseases Recruiting
Bordeaux, France, 33076
Contact: Guilhem Solé, MD    05 57 82 13 80    guilhem.sole@chu-bordeaux.fr   
Contact: Fanny Duval, MD    05-57-82-12-52    fanny.duval@chu-bordeaux.fr   
Sub-Investigator: Gwendal Le Masson, PU-PH         
Sub-Investigator: Stéphane Mathis, MD         
Sub-Investigator: Antoine Soulages, MD         
Sponsors and Collaborators
University Hospital, Bordeaux
University of Bordeaux
Investigators
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Principal Investigator: Guilhem Solé, MD University Hospital Bordeaux, France

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Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT03720275     History of Changes
Other Study ID Numbers: CHUBX 2016/35
First Posted: October 25, 2018    Key Record Dates
Last Update Posted: December 3, 2018
Last Verified: November 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Bordeaux:
proportion, TTR-FAP, study, neuropathy

Additional relevant MeSH terms:
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Peripheral Nervous System Diseases
Amyloidosis
Amyloid Neuropathies
Amyloid Neuropathies, Familial
Neuromuscular Diseases
Nervous System Diseases
Proteostasis Deficiencies
Metabolic Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Amyloidosis, Familial
Metabolism, Inborn Errors