Hereditary Amyloidosis, Transthyretin-Related
Conditions
Keywords
transthryretin, Hereditary transthyretin amyloidosis, TTRv, familial amyloid polyneuropathy
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.
Interventions
DIAGNOSTIC_TESTneurofilament light chain
Blood test
DIAGNOSTIC_TESTIn-vivo Meissner Corpuscle imaging
Imaging
DIAGNOSTIC_TESTNerve conduction study
Nerve conduction study
Sponsors
University of Pennsylvania
Ionis Pharmaceuticals, Inc.
AstraZeneca
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
30 Years to 90 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORChafic Karam, MD
University of Pennsylvania
PRINCIPAL_INVESTIGATORBrian Drachman
University of Pennsylvania
PRINCIPAL_INVESTIGATORSami Khella, MD
University of Pennsylvania
PRINCIPAL_INVESTIGATORJanice Pieretti, MD
University of Pennsylvania
Outcome results
None listed