Exploring Biomarkers in Hereditary Transthyretin Amyloidosis

NCT05929209 | Recruiting

• 1 other identifier: 5470
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Hereditary transthyretin amyloidosis (ATTRv, v for variant) is a severe and heterogeneous systemic condition due to mutations in the transthyretin (TTR) gene. The availability of disease-modifying therapies has led to an urgent need to have reliable biomarkers capable of assessing the clinical severity of the disease and of monitoring the efficacy of pharmacological treatment. At the same time, early markers for the clinical onset of ATTRv amyloidosis in presymptomatic subjects are needed to enable earlier initiation of anti-amyloid therapy. In this project the investigators seek to achieve three main goals: to identify and validate disease severity biomarkers in symptomatic patients; to establish disease onset biomarkers of ATTRv amyloidosis in presymptomatic subjects; to explore new pathogenetic mechanisms underlying this multisystem disorder, such as mitochondrial dysfunction and immune response.

Conditions

Hereditary Transthyretin Amyloidosis

Keywords

hereditary transthyretin amyloidosis; neurogenetics; neuromuscular disorders; biomarkers; mitochondrial dysfunction

Outcome Measures

Primary Outcomes (6)

• Circulating disease biomarkers in ATTRv amyloidosis

  Validation of serum biomarkers of disease (DJ-1, cystatin C, calbindin, uromodulin, GDF-15 and NfL) in patients with ATTRv (baseline assessment). Change from baseline in serum levels of disease biomarkers (DJ-1, cystatin C, calbindin, uromodulin, GDF-15 and NfL) at different time points through week 96.

  Baseline, weeks 24, 48, 72, 96

• Neuropathological biomarkers in ATTRv amyloidosis

  Baseline assessment of intraepidermal nerve fiber density (IENFD). Change from baseline in intraepidermal nerve fiber density (IENFD) at week 96.

  Baseline, week 96

• Radiological biomarkers (muscle MRI) in ATTRv amyloidosis

  Baseline assessment of total fatty infiltration score and STIR sequences. Change from baseline in total fatty infiltration score and STIR sequences at week 96.

  Baseline, week 96

• Circulating disease biomarkers in presymptomatic individuals

  Change from baseline in serum levels of disease biomarkers (DJ-1, cystatin C, calbindin, uromodulin, GDF-15 and NfL) at different time points through week 96.

  Baseline, weeks 24, 48, 72, 96

• Neuropathological biomarkers in presymptomatic individuals

  Baseline assessment of intraepidermal nerve fiber density (IENFD). Change from baseline in intraepidermal nerve fiber density (IENFD) at week 96.

  Baseline, week 96

• Radiological biomarkers (muscle MRI) in presymptomatic individuals

  Baseline assessment of total fatty infiltration score and STIR sequences. Change from baseline in total fatty infiltration score and STIR sequences at week 96.

  Baseline, week 96

Secondary Outcomes (2)

• Inflammatory profile in ATTRv amyloidosis

  Baseline, week 96

• Mitochondrial dysfunction in ATTRv amyloidosis

  Baseline

Study Arms (1)

Assessment of disease biomarkers

EXPERIMENTAL

Diagnostic Test: Assessment of disease biomarkers

Interventions

Assessment of disease biomarkers DIAGNOSTIC_TEST

Assessment of serum, histological and radiological biomarkers

Assessment of disease biomarkers

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Molecularly defined patients with hereditary transthyretin amyloidosis, carrying TTR pathogenic variants
• Presymptomatic carriers of the pathogenic variants in TTR gene
• Subjects aged 18 years or older
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study

You may not qualify if:

• Inability to understand or unwilling to follow the study requirements including attendance at the study center, completion of questionnaires and participation in laboratory testing as called for by the protocol
• Inability to sign an informed consent
• Severe psychiatric diseases

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, ID, 00168, Italy

RECRUITING

MeSH Terms

Conditions

Amyloidosis, Hereditary, Transthyretin-Related; Neuromuscular Diseases; Mitochondrial Diseases

Condition Hierarchy (Ancestors)

Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Guido Alessandro Primiano

CONTACT

+39 0630154279; guidoalessandro.primiano@policlinicogemelli.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: June 7, 2023
• First Posted: July 3, 2023
• Study Start: May 1, 2023
• Primary Completion: December 31, 2025
• Study Completion: April 30, 2026
• Last Updated: September 24, 2024

Record last verified: 2024-09

Locations

IT (1)