Clinical trial NCT05311488: Early Detection of Neuropathy in ATTRv
Official title: Early Detection of Peripheral Neuropathy in Hereditary Transthyretin Amyloidosis
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Hereditary Amyloidosis, Transthyretin-Related
Keywords: transthryretin
Hereditary transthyretin amyloidosis
TTRv
familial amyloid polyneuropathy
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: Ionis Pharmaceuticals, Inc.
name: AstraZeneca
First posted: 2022-04-05
Enrollment: 47
Sex: ALL
Minimum age (years): 30
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: ATTRv symptomatic, asymptomatic and control.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Serum neurofilament light chain
timeFrame: 12 months
measure: Meissner corpuscles
timeFrame: 12 months
Secondary outcomes:
measure: Quantitative sensory testing
timeFrame: 12 months
measure: Neuropathy symptoms questionnaire
timeFrame: 12 months
measure: Neuropathy impairment score
timeFrame: 12 months
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Chafic Karam, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pennsylvania
name: Brian Drachman
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pennsylvania
name: Sami Khella, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pennsylvania
name: Janice Pieretti, MD
role: PRINCIPAL_INVESTIGATOR
References: