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ATTR-Cardiomyopathy Stabilization Following Tafamidis Therapy

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ClinicalTrials.gov Identifier: NCT04513600
Recruitment Status : Recruiting
First Posted : August 14, 2020
Last Update Posted : August 14, 2020
Sponsor:
Information provided by (Responsible Party):
Dr. Wojciech Mazur, The Christ Hospital

Brief Summary:

The study will investigate the stabilization effects of Tafamidis utilizing cardiac imaging cardiac magnetic resonance imaging (CMR). We propose to pursue the following specific aims:

  1. Utilize CMR to assess stabilization of ATTR after Tafamidis therapy based on ECV.
  2. Investigate LV myocardial mass, native T1, T2, and extracellular volume mapping after 12 month follow-up.
  3. Utilize CMR indices (feature tracking, FTCMR) to correlate to echocardiographic indices (speckle tracking echocardiography, STE).

Condition or disease Intervention/treatment
Transthyretin Amyloidosis Diagnostic Test: Cardiac MRI

Detailed Description:

We hypothesize that individuals with earlier stages (NYHA Class I and Class II) of ATTRwt and ATTRm will demonstrate stabilization and potential regression of ATTR following 1 year of Tafamidis. In addition, we hypothesize that there are there may be an underlying natural mechanism that the body uses to reduce further reduce amyloid burden once Tafamidis has been initiated. This speculation is based upon the improved quality of life assessments obtained from the previously conducted randomized trial of subjects following Tafamidis. We propose to pursue the following specific aims:

  1. Utilize CMR to assess stabilization of ATTR after Tafamidis therapy based on ECV.
  2. Investigate LV myocardial mass, native T1, T2, and extracellular volume mapping after 12 month follow-up.
  3. Utilize CMR indices (feature tracking, FTCMR) to correlate to echocardiographic indices (speckle tracking echocardiography, STE).

We will enroll 131 patients with confirmed ATTR. All subjects enrolled will have a baseline comprehensive echocardiogram for demonstration of echocardiographic features of ATTR (end-diastolic IVS >12 mm) will be used to identify patients potentially with ATTR. Patients will be screened to exclude light chain amlyoidosis by either measuring the proportion of kappa: lambda light chains with the serum free light chain assay, and testing for immunofixation electrophoresis of serum and urine. Once patient has confirmed diagnosis of ATTR (PYP positive scoring >1.5 ratio) and undergone all baseline testing they will be ask to enroll in the study. Genetic testing (Invitae) will performed to further distinguish between mutation and wild type All patients will be required to sign informed consent agreeing to follow up testing at 1 year.

All subjects will undergo a comprehensive baseline echocardiogram, followed by a baseline CMR including native T1, T2, first pass perfusion, ECV for patients with GFR >30. Patients with GFR <30 only native T1 and T2 values will be extracted. If patients undergo implanted cardiac device during Tafamidis therapy, follow up CMR will only consist of featuring tracking values and LV mass. The LV mass and CMR feature tracking values will be extracted from all CMR studies. After one year of Tafamidis therapy, subjects will return to initial facility where testing was preformed to undergo a follow up CMR study.

We propose to collect and store blood samples for future analyses as directed by emerging evidence in there may be biomarkers yet identified for earlier detection of this disease. In view of recent advances in genomics and innovative technologies, including next-generation sequencing, we consider that the study is a resource for discovering novel genetic variants linked to ATTR.

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Study Type : Observational
Estimated Enrollment : 131 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: Transthyretin Amyloid Cardiomyopathy: Stabilization Assessed by Cardiac Magnetic Resonance
Actual Study Start Date : August 1, 2020
Estimated Primary Completion Date : August 1, 2022
Estimated Study Completion Date : August 1, 2023



Intervention Details:
  • Diagnostic Test: Cardiac MRI
    Lab work: Hs- Troponin, Serum NT-proBNP CMR: Native T1, Native T2, ECV, strain and strain rate.
    Other Name: Blood sample


Primary Outcome Measures :
  1. Stabilization of ATTR-CM [ Time Frame: 1 year ]
    stabilization as defined by reduction in ECV on CMR after one year of Tafamidis therapy



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
131 patients diagnosed with ATTR-CM being treated with Tafamidis
Criteria

Inclusion Criteria:

  • Patients will be included if they meet the following criteria:

    • 18 and 90 years of age
    • Transthyretin amyloid cardiomyopathy (ATTRwt or ATTRm) confirmed by genetic testing and/or presence of transthyretin precursor protein confirmed on immunohistochemical analysis, and/or scintigraphy
    • History of heart failure (NYHA I, II, or III)
    • Agreeable to treatment with Tafamidis

Exclusion Criteria:

  • Patients will be excluded if any one of the following criteria are not met:

    • Heart failure not due to transthyretin amyloid cardiomyopathy
    • New York Heart Association (NYHA) class IV heart failure
    • Presence of light-chain amyloidosis (serum or urine)
    • Implanted cardiac device
    • Previous treatment with Tafamidis/ Patisrian/ Diflusnial/ Inotersen

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04513600


Contacts
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Contact: Wojciech Mazur, MD 513-206-1120 wojciech.mazur@thechristhospital.com
Contact: Cassady Palmer, BS 513-585-1400 cassady.palmer@thechristhospital.com

Locations
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United States, Ohio
The Christ Hospital Recruiting
Cincinnati, Ohio, United States, 45219
Contact: Wojciech Mazur, MD    513-206-1120    wojciech.mazur@thechristhospital.com   
Contact: Cassady Palmer, BS    513-585-1400    cassady.palmer@thechristhospital.com   
Sponsors and Collaborators
The Christ Hospital
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Responsible Party: Dr. Wojciech Mazur, Director of Advanced Cardiac Imaging, The Christ Hospital
ClinicalTrials.gov Identifier: NCT04513600    
Other Study ID Numbers: 20-02
First Posted: August 14, 2020    Key Record Dates
Last Update Posted: August 14, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Cardiomyopathies
Amyloidosis
Heart Diseases
Cardiovascular Diseases
Proteostasis Deficiencies
Metabolic Diseases