Asymptomatic Carrier State, Hereditary Amyloidosis, Transthyretin-Related
Conditions
Brief summary
This is a single-center observational study evaluating the potential value of NfL as a biomarker for diagnosis, detection of disease onset, monitoring of disease progression, and treatment response in asymptomatic carriers of TTR variants and symptomatic hATTR amyloidosis patients with polyneuropathy.
Detailed description
In this study, participants' data will be extracted from their medical records or collected based on clinical and laboratory assessments during routine visits, per the site's standard of care. Blood samples collected from the participants during routine visits will also be used for analysis. The study will be conducted in two parts: Cross-Sectional part during which a single measurement of NfL levels will be performed using blood samples collected from asymptomatic carriers, and symptomatic hATTR amyloidosis patients; Longitudinal part during which measurements of NfL levels will be performed over time using blood samples (already collected from the participants during routine visits) from asymptomatic carriers and patients with symptomatic hATTR amyloidosis.
Interventions
OTHERStandard of Care
This is an observational study. No study drug will be administered as a part of the study, participants will be treated according to the decision of the treating physician.
Sponsors
Alnylam Pharmaceuticals
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
\- Carrier of a documented pathogenic TTR variant confirmed with genotyping with predicted disease onset within 5 years and not diagnosed with hATTR amyloidosis with polyneuropathy OR Confirmed diagnosis of hATTR amyloidosis with polyneuropathy with a documented TTR variant confirmed with genotyping \- Participant is able to understand the study and does not oppose participating in the study after reviewing the content of the PIS provided.
Exclusion criteria
* A known condition (other than hATTR amyloidosis) that can cause nerve damage and affect NfL levels * Estimated glomerular filtration rate (eGFR) \<45 milliliters per minute per 1.73 meters squared (mL/min/1.73 m\^2) * Currently enrolled in a clinical study for any investigational agent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| NfL Levels in Asymptomatic Carriers of a TTR Variant and Symptomatic hATTR Patients With Polyneuropathy at Baseline | Baseline |
| Change in NfL Levels Over Time in Asymptomatic Carriers of a TTR Variant and Symptomatic hATTR Patients With Polyneuropathy | Up to 24 months |
Secondary
| Measure | Time frame |
|---|---|
| Correlation Between the NfL Levels and Various Biological and Clinical Activity Parameters in Asymptomatic Carriers of a TTR Variant and Symptomatic hATTR Patients With Polyneuropathy at Baseline | Baseline |
| Correlation Between the Change in NfL Levels and Various Biological and Clinical Activity Parameters in Asymptomatic Carriers of a TTR Variant and Symptomatic hATTR Patients With Polyneuropathy | Up to 24 months |
| Comparison of the Measured NfL Levels to the Normal Levels Expected to be Seen in the General Population by Using the Existing Reference Ranges and Databases | Baseline, 24 months |
| Time to Onset of Active Disease in Asymptomatic Carriers of TTR Variants | Up to 24 Months |
| Disease Progression in Symptomatic hATTR Amyloidosis Patients with Polyneuropathy | Up to 24 Months |
Countries
France
Outcome results
None listed