Monitoring of Early Disease Progression in Hereditary Transthyretin Amyloidosis

Amyloidosis Clinical Trial

— MED-hATTR  

Official title:

Monitoring of Early Disease Progression in Hereditary Transthyretin Amyloidosis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03431896
• Other study ID #: 17-1301
• Status: Active, not recruiting
• Start date: February 1, 2018
• Est. completion date: December 31, 2026

Study information

• Verified date: April 2024
• Source: The Cleveland Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study measures circulating, misfolded ATTR oligomers in asymptomatic ATTRm amyloidosis genetic carriers longitudinally over five years.

Description:

Recent advances in genetic testing have allowed for pathogenic mutation identification in family members of affected individuals prior to onset of symptoms. While the presence of mutation and the corresponding TTR kinetic stability have been directly linked to disease development, the molecular drivers of tissue specific degeneration have not been defined. We hypothesize that soluble misfolded TTR oligomer species may be circulating within the blood of these patients possibly years prior to amyloid deposition and could serve as an early biomarker and/or driver for disease development. In this line, The Scripps Research Institute has developed a peptide-based probe that specifically labels and integrates into misfolded TTR oligomers allowing the relative circulating concentration in the bloodstream to be determined. Longitudinal monitoring of untreated, asymptomatic TTR amyloid genetic carriers utilizing the Scripps probe is likely to provide novel insight into early disease progression. We also plan to utilize the Scripps probe to monitor disease progression in TTR amyloid genetic carriers currently undergoing treatment by observing how treatments affect the circulating misfolded TTR oligomers. Through enhanced understanding of early disease progression and treatment efficacy, our hope is to limit amyloid accumulation in cardiac and nerve tissue and delay the development of the invariably fatal TTR amyloid cardiomyopathy/neuropathy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: December 31, 2026
• Est. primary completion date: September 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Patients with known hereditary ATTR amyloidosis genetic mutations as identified by genetic testing.

Exclusion Criteria:

• Patients with ATTR amyloidosis identified as wild-type.

Related Conditions & MeSH terms

• AL Amyloidosis
• Amyloid
• Amyloid - Primary
• Amyloid Cardiomyopathy
• Amyloid Neuropathies
• Amyloid Neuropathies, Familial
• Amyloidosis
• Cardiomyopathies
• Disease Progression
• Immunoglobulin Light-chain Amyloidosis
• Transthyretin Amyloidosis

Locations

Country	Name	City	State
United States	Cleveland Clinic	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
The Cleveland Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Average % change in oligomers in patients with new onset TTR amyloid symptoms	Change (%) for oligomer level at the time of TTR amyloid symptoms compared to baseline	Annually over 5 years
Secondary	% change of oligomer levels relative to baseline level in patients with ATTR specific medication changes	Change (%) for oligomer level at the time of ATTR specific medication changes compared to baseline	Annually over 5 years