Early Detection of Neuropathy in ATTRv (EDONA)

Early Detection of Peripheral Neuropathy in Hereditary Transthyretin Amyloidosis

The purpose of the study is to evaluate and compare different tools that are used to detect evidence of peripheral neuropathy in patients with TTRv.

Study Overview

• Status: Active, not recruiting
• Conditions: Hereditary Amyloidosis, Transthyretin-Related
• Intervention / Treatment: Diagnostic test: neurofilament light chain; Diagnostic test: In-vivo Meissner Corpuscle imaging; Diagnostic test: Nerve conduction study

Detailed Description

Early detection of peripheral neuropathy in patients with TTRv is important to support initiation of therapy that alters the course of the disease. Current tools used to detect peripheral neuropathy may not be sensitive, especially in very early and distal peripheral neuropathy. This study will compare different methods of assessing for peripheral neuropathy including using in-vivo reflectance confocal microscopy to assess for meissner corpuscles, serum neurofilament light chain, quantitative sensory testing, neuropathy impairement scores, nerve conduction studies and quality of life and symptoms questionnaires.

• Study Type: Observational
• Enrollment (Actual): 47

Contacts and Locations

• Study Contact: Name: Daniel Corr; Phone Number: 2156622692; Email: CorrD@pennmedicine.upenn.edu
• Study Contact Backup: Name: Kelsey Moulton; Phone Number: 2156140027; Email: Kelsey.Moulton@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

ATTRv symptomatic, asymptomatic and control.

Description

Inclusion Criteria:

1. Age 30 years or older
2. Patients with known TTR mutations and neuropathy, patients with TTR mutation and no symptoms within less than 10 years of typical onset of disease., or healthy persons without neuropathy

Exclusion Criteria:

1. Patients with neuropathy other than TTR amyloid
2. Subjects with risk factors for neuropathy (diabetes, history of neuropathy in the family, neurotoxic drugs) or with neurological disorder associated with elevated NFL

The following distribution of age ranges will be considered when enrolling healthy participants:

• 5 patients age 30-40
• 5 patients age 40-50
• 5 patients age 50-60
• 5 patients age 60-70

The following age limitations will be in place for asymptomatic TTR carriers. The idea is to select patients that are likely to develop evidence of disease within the next 10 years.

• Non V122I mutation> or =30
• V122I> or = 55

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Symptomatic TTRv; Patients with known TTR mutations and neuropathy	Diagnostic test: neurofilament light chain; Blood test; Diagnostic test: In-vivo Meissner Corpuscle imaging; Imaging; Diagnostic test: Nerve conduction study; Nerve conduction study
Asymptomatic TTRv; Patients with TTR mutation and no symptoms within less than 10 years of typical onset of disease	Diagnostic test: neurofilament light chain; Blood test; Diagnostic test: In-vivo Meissner Corpuscle imaging; Imaging; Diagnostic test: Nerve conduction study; Nerve conduction study
Healthy controls; Age and sex matched healthy controls without neuropathy or other neurological disorder.	Diagnostic test: neurofilament light chain; Blood test; Diagnostic test: In-vivo Meissner Corpuscle imaging; Imaging; Diagnostic test: Nerve conduction study; Nerve conduction study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Serum neurofilament light chain	Change in sesrum neurofilament light chain concentration at 12 months	12 months
Meissner corpuscles	Change in Meissner corpuscles density at 12 months	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative sensory testing	Testing of vibratory sensation using a tuning fork, testing of light touch using neurofilament	12 months
Neuropathy symptoms questionnaire	Questionnaire that assess symptoms of neuropathy and severity.	12 months
Neuropathy impairment score	Neurological examination reporting motor strength, reflexes and sensation. Scale ranges from 0 (normal) to 244, with a higher score indicating greater impairment.	12 months

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: AstraZeneca; Ionis Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Chafic Karam, MD, University of Pennsylvania; Principal Investigator: Brian Drachman, University of Pennsylvania; Principal Investigator: Sami Khella, MD, University of Pennsylvania; Principal Investigator: Janice Pieretti, MD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2022
• Primary Completion (Estimated): June 14, 2025
• Study Completion (Estimated): February 14, 2029

Study Registration Dates

• First Submitted: March 16, 2022
• First Submitted That Met QC Criteria: March 25, 2022
• First Posted (Actual): April 5, 2022

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: familial amyloid polyneuropathy; transthryretin; Hereditary transthyretin amyloidosis; TTRv
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Proteostasis Deficiencies; Metabolism, Inborn Errors; Amyloidosis; Amyloidosis, Familial
• Other Study ID Numbers: 849579

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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