Neuropathy in Patients Monitored for Wild-type TTR Cardiac Amyloidosis (Non-mutated) (N-SAC)

Prospective Study to Investigate Neuropathy in Patients Monitored for Wild-type TTR Cardiac Amyloidosis (Non-mutated)

Transthyretin (TTR) amyloidosis is a rare disabling disorder that can be hereditary or sporadic. Depending on the form, various tissues are affected. While in hereditary cases, neuropathy is predominant, cardiac impairment is the main manifestation in the sporadic form.

The main objective of this project is to evaluate the proportion of patients with neuropathy in a population of patients with a non-mutated TTR amyloid cardiopathy condition.

Study Overview

• Status: Completed
• Conditions: Wild-type Amyloid Cardiopathy
• Intervention / Treatment: Procedure: electromyogram

Detailed Description

Transthyretin (TTR) amyloidosis belongs to a group of severe and multi-systemic diseases caused by an extracellular accumulation of fibrillar proteins arranged in beta-pleated sheets. This pathology can be hereditary (mutations in the TTR gene) or sporadic. Depending on the form, various tissues are affected: peripheral nervous system (leading to neuropathy, especially vegetative), heart, kidney... While in forms linked to TTR mutations neuropathy is the main manifestation, in the sporadic form (also called wild-type), the cardiac impairment is predominant. Other organ damages are rarely reported in this second form. In the THAOS registry (Coelho T. et al, 2013), a clinical peripheral neuropathy is reported in 28.4% out of 67 patients with the sporadic form of the disease, although the authors do not provide a precise description of the neuropathy type. We propose to prospectively study patients with a wild-type amyloid cardiopathy condition to identify and describe the associated neuropathy. A pilot study conducted at the Bordeaux University Hospital demonstrated the feasibility and interest of this research: it showed the presence of an undetermined aetiology polyneuropathy in 35.7% out of 14 patients followed for senile cardiac amyloidosis.

Tafamidis is used on familial amyloid neuropathy and a recent study shows an effect on senile amyloid cardiopathy (Maurer MS et al., 2018) which strengthens the need to determine the frequency of neuropathies associated with wild-type amyloid cardiopathy and to type them more accurately.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33076
    • CHU de Bordeaux
  • Nantes, France, 44093
    • CHU de Nantes
  • Toulouse, France, 31059
    • CHU de Toulouse

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients of both gender, over 18 years old, with transthyretin amyloid cardiopathy according to one of the two American Heart Association definitions of 2016
• No mutation in the TTR gene
• Patients giving their free and informed consent to participate after information about the research
• Patients affiliated to or benefiting from a social security scheme

Exclusion Criteria:

• Patients with chronic neuropathy related to a known aetiology
• Patients under guardianship or curatorship

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: proportion of patients with neuropathy; to prospectively study patients with a wild-type amyloid cardiopathy condition to identify and describe the associated neuropathy

Procedure: electromyogram; Patients meeting the criteria will be seen in consultation with standardized interview and clinical examination. An electromyogram will be then carried out to check for the presence of neuropathy. Finally, for patients diagnosed with neuropathy, a biological check-up to look for another cause of neuropathy will be performed. In patients who already had an EMG as part of their medical follow-up, the examination will not be repeated if it strictly meets the conditions of the minimum protocol and if it was done within the year prior to inclusion. In patients who already had an identical biological assessment in the year prior to inclusion, the sample will not be taken.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of a clinical and/or electrophysiological neuropathy	The diagnosis of peripheral neuropathy should meet P.J. Dyck's definition of peripheral neuropathy (New England Journal of Medicine, 1982), based on: the clinical judgment resulting from the standardized clinical examination (carried out by an expert neurologist) and according to the HAS recommendations on the diagnosis of peripheral neuropathies;; electrophysiological abnormalities, interpreted in the clinical context, after an examination carried out by an expert neurophysiologist.	within 6 months of inclusion (at the time of the electromyogram)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical data of patients with polyneuropathy with no identified etiology: Epidemiological characteristics	age, sex, age at diagnosis, age at assessment	within 6 months of inclusion (at the time of the electromyogram)
Clinical data of patients with polyneuropathy with no identified etiology: history characteristics	carpal tunnel, diabetes, narrow cervical canal, alcohol consumption, radiculalgia in the lower limbs	within 6 months of inclusion (at the time of the electromyogram)
Clinical data of patients with polyneuropathy with no identified etiology: Heart attack	Heart failure ( yes/no), pacemaker (Yes/no) and Functional classification of heart disease according to the New York Heart Association (NYHA) score. The NYHA score is a classification in 4 stages of increasing severity is proposed by the New York Heart Association, it is based on the intensity of the symptoms: I: Asymptomatic, discomfort during exceptional efforts. II: Moderate discomfort for significant efforts. III: Discomfort felt during moderate efforts. IV: Discomfort during the slightest effort or at rest. Référence: Hurst Hurst JW, Morris DC, Alexander RW. The use of the New York Heart Association's classification of cardiovascular disease as part of the patient's complete Problem List. Clin Cardiol . JW, Morris DC, Alexander RW. L'utilisation de la New York Heart Association de classification du des maladies cardiovasculaires dans le cadre du patient compléter la liste des problèmes. Clin Cardiol. 1999 Jun ;22 (6):385-90.	within 6 months of inclusion (at the time of the electromyogram)
Clinical data of patients with polyneuropathy with no identified etiology: Clinical scores - KARNOFSKI index	The KARNOFSKY index is used to assess the general condition of the patient: it is a scale from 0 to 100, the maximum representing the absence of complaints related to the disease.	within 6 months of inclusion (at the time of the electromyogram)
Clinical data of patients with polyneuropathy with no identified etiology: Clinical scores - NIS-LL-	Neuropathy Impairment Score-Lower Limb (NIS-LL): this is a score out of 88, the minimum (0) representing an asymptomatic patient	within 6 months of inclusion (at the time of the electromyogram)
Clinical data of patients with polyneuropathy with no identified etiology: Clinical scores - ONLS-	The Overall Neuropathy Limitation Scale (ONLS) is used to assess the functional impact of neuropathy: score out of 12, the minimum (0) representing a patient without any functional impairment related to his neuropathy.	within 6 months of inclusion (at the time of the electromyogram)
Clinical data of patients with polyneuropathy with no identified etiology: Clinical scores - RODS-	The Rasch Score-built Overall Disability Scale (RODS) is used to assess the impact of neuropathy on activities of daily living: it is a scale from 0 to 48 with the maximum representing a patient asymptomatic.	within 6 months of inclusion (at the time of the electromyogram)
Clinical data of patients with polyneuropathy with no identified etiology: Clinical scores - CADT-	The Compound Autonomic Dysfunction Test (CADT) is used to assess vegetative impairment: it is rated out of 16 maximum if normal (erectile dysfunction will not be taken into account in men).	within 6 months of inclusion (at the time of the electromyogram)
Clinical data of patients with polyneuropathy with no identified etiology: Clinical scores -MoCA-	The Montreal Cognitive Assessment (MoCA) is used for a cognitive assessment: out of 30, the maximum being a subject without impairment.	within 6 months of inclusion (at the time of the electromyogram)
Clinical data of patients with polyneuropathy with no identified etiology: Electrophysiological data	This data includes: Motor and / or sensory impairment; Axonal and / or demyelinating character; Length-dependent or non-length-dependent character; Topography of the disease	within 6 months of inclusion (at the time of the electromyogram)
Estimation of the frequency of the presence of neuropathy in our study population in order to compare it to a reference population	Estimation of the frequency of the presence of neuropathy in our study population in order to compare it to a reference population	24 months

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Investigators: Principal Investigator: Guilhem SOLE, MD, Université Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2021
• Primary Completion (Actual): March 31, 2023
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: March 26, 2021
• First Submitted That Met QC Criteria: March 30, 2021
• First Posted (Actual): April 2, 2021

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: October 5, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: neuropathy; wild-type amyloid cardiopathy; descriptive study
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Metabolic Diseases; Proteostasis Deficiencies; Heart Diseases; Amyloidosis
• Other Study ID Numbers: CHUBX 2020/27

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No