Determining the Association of TTR Stabilizing Therapy With Circulating TTR Amyloid Aggregates Over Time in Patients With ATTR-CM: Longitudinal Biomarker Study

NCT07196839 | Recruiting

• 1 other identifier: STU-2024-1119
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to determine the association of clinically prescribed, on-label, TTR stabilizing therapy (e.g. tafamidis or acoramidis) with levels of circulating transthyretin amyloid aggregates (TAAs, a surrogate for amyloid disease activity) measured serially over time in patients with transthyretin cardiac amyloidosis (ATTR-CA). To accomplish this objective, the hypothesis that TTR stabilizing therapy will be associated lower circulating TAAs over time will be tested. Completion of this study will advance the understanding of the influence of ATTR-CA treatments on circulating evidence of amyloidosis and justify the role of blood testing to monitor treatment response in patients with ATTR-CA.

Conditions

Transthyretin (TTR) Amyloid Cardiomyopathy

Keywords

transthyretin; tafamidis; acoramidis; amyloidosis

Outcome Measures

Primary Outcomes (1)

• Serial blood levels of circulating TTR amyloid aggregates (TAAs)

  The primary hypothesis is that TTR stabilizing therapy will lower circulating evidence of amyloidosis in patients with ATTR-CA from baseline to 3 months. In addition, the study team expects that there will be a time\*treatment interaction identifying that treatment initiation will have a differential effect on serial levels of circulating s over time than those currently on treatment. These observations will support the role for measuring circulating TAAs to monitor treatment response in ATTR-CA.

  Baseline, 1 month (+/- 5 days), and 3 months (+/- 5 days).

Study Arms (2)

Taking on-label TTR stabilizing treatment

Taking on-label TTR stabilizing treatment for \>14 days prior to enrollment

Initiating on-label TTR stabilizing treatment

Initiating on-label TTR stabilizing treatment within 5 days after enrollment

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

ATTR-CA patients with a diagnosis of heart failure.

You may qualify if:

• Men and women ages 30-80 who have symptomatic ATTR-CA as determined by a history of HF (this will be assessed by study personnel and defined as : 1) history of hospitalization within the previous 12 months for management of HF; 2) an elevated B-type natriuretic peptide level ≥100 pg/mL or NT-proBNP ≥360 pg/mL within the previous 12 months; or 3) a clinical diagnosis of HF from a treating clinician)
• ATTR-CA previously diagnosed histologically by amyloid staining and tissue typing with immunohistochemistry or mass spectrometry or by bone scintigraphy in without abnormal M-protein
• TTR gene sequencing confirming the TTR genotype has resulted or is pending
• Enrollment will be stratified by n/N=30/50 starting on-label TTR-stabilizing therapy (e.g. tafamidis) within 5 days after enrollment or by n/N=20/50 of those currently taking TTR-stabilizing therapy

You may not qualify if:

• Other known causes of cardiomyopathy
• History of light-chain cardiac amyloidosis
• Cardiac transplantation
• Liver transplantation
• Has taken patisiran in the past 90 days, or inotersen in the past 180 days, has ever taken vutrisiran, or is participating in a clinical trial for ATTR treatments
• Estimated glomerular filtration rate ≤30 mL/min/1.73 m2
• Anticipated gaps in ATTR-CA treatment for 3 months after enrollment

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• University of Texas Southwestern Medical Center: lead

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75248, United States

RECRUITING

Related Publications (1)

• Pedretti R, Wang L, Hanna M, Benson MD, Grodin JL, Tang WHW, Masri A, Saelices L. Detection of Circulating Transthyretin Amyloid Aggregates in Plasma: A Novel Biomarker for Transthyretin Amyloidosis. Circulation. 2024 May 21;149(21):1696-1699. doi: 10.1161/CIRCULATIONAHA.123.067225. Epub 2024 May 20. No abstract available.

  PMID: 38768274 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood (plasma and serum)

MeSH Terms

Conditions

Amyloid Neuropathies, Familial; Amyloidosis

Condition Hierarchy (Ancestors)

Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Amyloid Neuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amyloidosis, Familial; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Proteostasis Deficiencies

Study Officials

• Justin Grodin, MD MPH

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jerah Sanchez

CONTACT

214-645-7303; jerahmarie.sanchez@utsouthwestern.edu

Amy Browning

CONTACT

Amy.Browning@utsouthwestern.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: September 19, 2025
• First Posted: September 29, 2025
• Study Start: December 31, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: January 7, 2026

Record last verified: 2026-01

Locations

US (1)