- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03720275
Early and Systematic Screening in Chronic Neuropathy (TTR-FAP)
Evaluation of a New Diagnostic Approach to Familial Amyloid Neuropathy by Mutation of the TTR Gene in a Population of Idiopathic Chronic Neuropathies
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Bordeaux, France, 33076
- Reference center for neuromuscular diseases
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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.
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Diagnosis of TTR-FAP
Time Frame: Genetic analyzes will be performed every three months from the first inclusion
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Proportion of TTR-FAP in the 130 patients with chronic neuropathy of unknown aetiology
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Genetic analyzes will be performed every three months from the first inclusion
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Age of patient at diagnosis
Time Frame: at the inclusion visit
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at the inclusion visit
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History of dysautonomias
Time Frame: at the inclusion visit
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History of dysautonomias at the interview
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at the inclusion visit
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Signs of dysautonomias
Time Frame: at the inclusion visit
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signs of dysautonomias at the interview
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at the inclusion visit
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Weight of patient
Time Frame: at the inclusion visit
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weight
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at the inclusion visit
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Height of patient
Time Frame: at the inclusion visit
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height
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at the inclusion visit
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Motor deficit of the lower limbs evaluated by a subscore of the Neuropathy Impairment Scale (NIS)
Time Frame: at the inclusion visit
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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.
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at the inclusion visit
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Motor deficit of the upper limbs evaluated by a subscore of the Neuropathy Impairment Scale (NIS)
Time Frame: at the inclusion visit
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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.
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at the inclusion visit
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Sensory deficit evaluated by a subscore of the Neuropathy Impairment Scale (NIS)
Time Frame: at the inclusion visit
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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.
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at the inclusion visit
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Presence / Absence of reflexes osteo-tendinous evaluated by a subscore of the Neuropathy Impairment Scale (NIS)
Time Frame: at the inclusion visit
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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.
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at the inclusion visit
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Presence of orthostatic hypotension
Time Frame: at the inclusion visit
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Blood pressure measurement by the nurse
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at the inclusion visit
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Dysautonomia score
Time Frame: at the inclusion visit
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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
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at the inclusion visit
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Rasch-built Overall Disability Scale (RODS) score
Time Frame: at the inclusion visit
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Score at the RODS, a functional scale that captures daily activity and social participation limitations in patients affected by polyneuropathy (self-questionnaire)
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at the inclusion visit
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Overall Neuropathy Limitations Scale (ONLS) score
Time Frame: at the inclusion visit
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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)
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at the inclusion visit
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Electroneuromyography findings (ENMG): axonal, demyelinating or mixed neuropathy).
Time Frame: at the inclusion visit
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at the inclusion visit
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Guilhem Solé, MD, University Hospital Bordeaux, France
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Nervous System Diseases
- Genetic Diseases, Inborn
- Neuromuscular Diseases
- Neurodegenerative Diseases
- Proteostasis Deficiencies
- Metabolism, Inborn Errors
- Heredodegenerative Disorders, Nervous System
- Amyloidosis, Familial
- Peripheral Nervous System Diseases
- Amyloidosis
- Amyloid Neuropathies
- Amyloid Neuropathies, Familial
Other Study ID Numbers
- CHUBX 2016/35
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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