Monitoring of Early Disease Progression in Hereditary Transthyretin Amyloidosis (MED-hATTR)

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

Study Overview

• Status: Completed
• Conditions: AL Amyloidosis; Amyloidosis; Amyloid Neuropathies, Familial; Amyloid; Transthyretin Amyloidosis; Amyloid Cardiomyopathy; Amyloid - Primary

Detailed 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.

• Study Type: Observational
• Enrollment (Actual): 37

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants will be identified through clinical practice and from Amyloid support groups

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Primary; 1.) To evaluate the relative amount of misfolded ATTR oligomers in asymptomatic ATTR amyloid genetic carriers and correlate their levels with clinical symptoms and outcomes.; Determine if misfolded ATTR oligomers are elevated compared to healthy control data obtained by Scripps during probe development; Describe the levels longitudinally; Determine if treatment with ATTR-specific medications (examples: diflunisal, doxycycline, ursodiol, tauroursodeoxycholic acid (TUDCA), green tea extract, curcumin, tafamidis, inotersen, patisiran) lead to reduction in the probe levels in those with elevated levels at baseline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
% 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

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Investigators: Principal Investigator: Mazen A Hanna, MD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2018
• Primary Completion (Actual): March 9, 2026
• Study Completion (Actual): March 9, 2026

Study Registration Dates

• First Submitted: February 7, 2018
• First Submitted That Met QC Criteria: February 7, 2018
• First Posted (Actual): February 13, 2018

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neoplasms; Neuromuscular Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Immune System Diseases; Peripheral Nervous System Diseases; Neoplasms by Histologic Type; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Heredodegenerative Disorders, Nervous System; Neoplasms, Plasma Cell; Paraproteinemias; Proteostasis Deficiencies; Amyloid Neuropathies; Amyloidosis, Familial; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Immunoglobulin Light-chain Amyloidosis; Alzheimer Disease; Amyloidosis; Amyloid Neuropathies, Familial; Amyloidosis, Hereditary, Transthyretin-Related
• Other Study ID Numbers: 17-1301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No