Early Detection of Neuropathy in ATTRv

Active, not recruiting

• Conditions: Hereditary Amyloidosis, Transthyretin-Related
• Interventions: Diagnostic Test: neurofilament light chain; Diagnostic Test: In-vivo Meissner Corpuscle imaging; Diagnostic Test: Nerve conduction study

• Registration Number: NCT05311488
• Lead Sponsor: University of Pennsylvania

Brief Summary

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.

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 Timeline

• Study Start: 2022-02-14
• Study First Submitted: 2022-03-16
• Study First Submitted QC: 2022-03-25
• Study First Posted: 2022-04-05
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-10
• Last Update Posted: 2025-04-15
• Primary Completion: 2025-06-14
• Study Completion: 2029-02-14

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 47

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Change in Serum neurofilament light chain	12 months	Change in Serum neurofilament light chain concentration at 12 months
Meissner corpuscles	12 months	Change in Meissner corpuscles density at 12 months

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States