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: Completed
• 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 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: Yes

• Sampling Method: Non-Probability Sample

Study Population

ATTRv symptomatic, asymptomatic and control.

Description

Inclusion Criteria:

Patients with known TTR mutations and neuropathy

1. Patients with TTR mutation and no symptoms within less than 10 years of typical onset of disease

2. Age criteria must meet the following:

   • Non V122I mutations, Age 40 or older.
   • V122 I mutations, 55 or older.

Healthy persons without neuropathy

1. 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
2. Healthy control subjects for this study are defined as subjects with no symptoms of neuropathy or risk factors for neuropathy such as family history of hereditary neuropathy, chemotherapy, diabetes, autoimmune disease, or vitamin deficiency. Their status will be verified by medical records review.

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

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
Meissner corpuscles	Change in Meissner corpuscles density at 12 months	12 months
Change in Serum neurofilament light chain	Change in Serum neurofilament light chain concentration 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 (Actual): November 1, 2025
• Study Completion (Actual): February 14, 2026

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 12, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: familial amyloid polyneuropathy; transthryretin; Hereditary transthyretin amyloidosis; TTRv
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Peripheral Nervous System Diseases; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Proteostasis Deficiencies; Amyloid Neuropathies; Amyloidosis, Familial; Amyloidosis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Amyloid Neuropathies, Familial; Amyloidosis, Hereditary, Transthyretin-Related; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Neurological; Electrodiagnosis; Nerve Conduction Studies
• 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