Phenotyping and Characterization of wtATTR-CM (TRACE 1)

Quality of Life Clinical Trial

Official title:

Phenotyping and Characterization of Danish Wild-type Transthyretin Amyloidosis Cardiomyopathy Patients: A Cross-sectional Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06291805
• Other study ID #: 1-10-72-189-23
• Status: Recruiting
• Start date: February 20, 2024
• Est. completion date: December 2025

Study information

• Verified date: February 2024
• Source: Aarhus University Hospital Skejby
• Contact: Sie Kronborg Fensman, MD
• Phone: +45 30 48 88 85
• Email: siefensman[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Descriptive cross-sectional study on 100 consecutive ATTRwt-CM patients reflecting all NAC stages aiming primarily to investigate ATTRwt-CM patient's quality of life (QoL) measures and their relation to ATTRwt-CM severity. Secondarily aiming to investigate the possibility to measure misTTR and fragTTR in plasma and urine and to detect fragTTR in endomyocardial biopsies from ATTRwt-CM patients. To investigate whether misTTR and fragTTR levels are correlated with ATTRwt-CM severity.

Description:

Hypothesis: 1. We hypothesize that more severe wild-type amyloidosis cardiomyopathy (ATTRwt-CM) according to clinical, biochemical, and diagnostic imaging parameters are correlated with worse quality of life (QoL) for patients. 2. We expect misfolded (misTTR) and/or fragmented transthyretin (fragTTR) to be measurable in plasma and/or urine and fragTTR to be detectable in endomyocardial biopsies from patients with ATTRwt-CM. We expect the values of misTTR and fragTTR to be correlated with the severity of ATTRwt-CM according to clinical, biochemical, and diagnostic imaging parameters. We expect the level of fragTTR from endomyocardial biopsies to be correlated with plasma levels of fragTTR. Method: ATTRwt-CM patients: Prospective inclusion of 100 consecutive ATTRwt-CM patients reflecting all NAC stages (40 patients from NAC disease stage 1, 40 patients from NAC disease stage II and 20 patients from NAC disease stage III). Patients will be recruited from the out-patient amyloidosis clinic at Aarhus University hospital. Patients will be thoroughly clinically assessed. Control patients: A control cohort of 20 age- and gender-matched heart-healthy patients will be included for comparison of total/mis-/fragTTR values. The investigating into QoL, bio markers and the analyses on cardiac MR imaging markers will hopefully provide us with tools to evaluate and monitor disease progression and response to treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Group 1: wtATTR-CM patients

Inclusion Criteria:

• Patients > 18 years diagnosed with ATTRwt-CM by:
• endomyocardial biopsy
• DPD scintigraphy with Perugini grade 2-3 where variant amyloidosis is ruled out due to genetic testing.
• Informed oral and written consent

Exclusion Criteria:

• AL amyloidosis (light-chain amyloidosis).
• Myelomatosis
• Waldenström macroglobulinemia Group 2: Control group

Inclusion Criteria:

• Patients > 18 years
• Informed oral and written consent

Exclusion Criteria:

• Known cardiovascular disease including ischemic heart disease, heart failure, atrial fibrillation, presence of a pacemaker, or malignant hypertension. Well-controlled hypertension is acceptable.
• Suspicion of cardiac amyloidosis assessed through clinical history, physical

examination, ECG, and echocardiography focusing on "red flags":

• Echocardiography with:
• Myocardial hypertrophy (septum >11 mm)
• Apical sparing in LV-GLS
• Infiltrative changes in the right ventricle free wall, thickened atrioventricular valves, or thickened atrial septum
• Symptoms of polyneuropathy
• Low voltage on ECG or discrepancy between left ventricular thickness and ECG amplitude indicative of low voltage
• Atrioventricular block (AV block)
• Bilateral carpal tunnel syndrome
• Surgery for spinal stenosis
• Elevated troponin I or NT-pro-BNP

Related Conditions & MeSH terms

• Amyloid Neuropathies, Familial
• Amyloidosis
• Cardiomyopathies
• Quality of Life
• Transthyretin Amyloid Cardiomyopathy
• Transthyretin Amyloidosis
• Wild-Type Transthyretin-Related (ATTR)Amyloidosis

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus	Arrhus N

Sponsors (2)

Lead Sponsor	Collaborator
Steen Hvitfeldt Poulsen	Novo Nordisk A/S

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Investigation of cardiac amyloidosis severity in patients with Wild-type Transthyretin Amyloidosis Cardiomyopathy.	Amyloid severity will be addressed using primarily NAC-stages and NYHA-class. Furthermore, we will use NT-pro-BNP, findings on echo (stroke volume, ejectionfraction and global longitudional strain) and finding on CMRI (LV mass, T1 myocardial values and extracellular volume).	Through study completion, 2 years.
Primary	Investigation of the relations between cardiac amyloid severity and patient quality of life in patients with Wild-type Transthyretin Amyloidosis Cardiomyopathy.	Quality of life will be addressed using KCCQ summary score, EQ-5D Utility score and VAS ranging score and ATTR-QOL total score.	Through study completion, 2 years.
Primary	Assessment of transthyretin and pathogenic fragments and relation to cardiac amyloid severity in patients with Wild-type Transthyretin Amyloidosis Cardiomyopathy	Transthyretin (TTR) will be measured as follows: total TTR, misfolded TTR and fragmented TTR in plasma and misfolded TTR and fragmented TTR in urine.	Through study completion, 2 years.
Secondary	Validation of a new amyloid specific questionnaire (ATTR-QoL) in comparison with Kansas City Cardiomyopathy Questionnaire (KCCQ)	Comparing ATTR-QOL total score to KCCQ summary score and EQ-5D Utility score and VAS ranging score.	Through study completion, 2 years.