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Screening for Cardiac Amyloidosis Using Nuclear Imaging for Minority Populations (SCAN-MP)

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ClinicalTrials.gov Identifier: NCT03812172
Recruitment Status : Not yet recruiting
First Posted : January 23, 2019
Last Update Posted : March 28, 2019
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Boston Medical Center
Harlem Hospital Center
The Scripps Research Institute
Information provided by (Responsible Party):
Mathew Maurer, Columbia University

Brief Summary:
In this study, the investigators will recruit a cohort of elderly Black and Hispanic patients with heart failure to define the number of patients who have cardiac amyloidosis by utilizing highly sensitive heart imaging and blood tests. The investigators will also explore differences in genetics and sex as they relate to heart failure disease progression in cardiac amyloidosis.

Condition or disease Intervention/treatment
Amyloid Cardiomyopathy, Transthyretin-Related Drug: 99mTc-PYP

Detailed Description:
Heart failure with preserved ejection fraction (HFpEF) disproportionately afflicts older Black and Hispanic Americans. ATTR cardiac amyloidosis (ATTR CA) is caused by myocardial deposition of misfolded transthyretin protein (TTR or prealbumin) and is classified by the genetics of TTR into wild-type (ATTRwt) or hereditary (hATTR or ATTRm). ATTR CA, irrespective of genotype, is an age-dependent, often unrecognized, mechanism underlying HFpEF. While hATTR CA results from point mutations that promote TTR misfolding and amyloid aggregation, factors that contribute to ATTRwt CA are not well defined. While previously thought to be untreatable, promising therapies that have been recently reported are most effective if administered early in disease course. Only a small proportion of individuals with wild-type TTR will develop ATTRwt CA, overwhelmingly reported in Caucasian males beyond age 60 years. However, as an autosomal protein, allele distribution is not sex specific. For hATTR, a substitution of isoleucine for valine (Val122Ile) is the most frequent TTR mutation in the US, observed exclusively in Black Americans with an allele frequency of 3.4%. But there are no data regarding the prevalence of ATTRwt CA in African Americans and no data for ATTR CA prevalence, irrespective of genotype, in the Hispanic population. One of the reasons for the knowledge deficit is the challenge of diagnosis. Endomyocardial biopsy, while nearly 100% sensitive and specific, is impractical as a screening test and genotyping alone of patients is insufficient to identify ATTR CA because wild-type patients develop disease. In this study, the investigators will use a highly accurate technique for ATTR CA identification using Tc99m-pyrophosphate (PYP) imaging that avoids the need for biopsy. Tc99m-PYP myocardial uptake can occur before echocardiographic or clinical changes, suggesting enhanced sensitivity. While studies using the technique have suggested that 10-15% of elderly hospitalized patients with HF may have ATTR CA, Tc99m-PYP has not been applied broadly in HF patients as a means to facilitate early diagnosis. In addition, the investigators will test the diagnostic accuracy of a point-of-care diagnostic tool that utilizes a novel biomarker, retinol binding protein 4 (RBP4), and an assay to measure TTR stability. The overall hypothesis is that a significant proportion of HF in elderly Blacks and Hispanics is caused ATTR CA. Using these non-invasive tests, the investigators will establish the prevalence of ATTR CA and explore the relationship between RBP4 concentration and TTR stability in a prospective cohort study of elderly Black and Hispanic Americans with HF.

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Study Type : Observational
Estimated Enrollment : 800 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Screening for Cardiac Amyloidosis Using Nuclear Cardiology for Minority Populations
Estimated Study Start Date : May 2019
Estimated Primary Completion Date : May 2024
Estimated Study Completion Date : May 2024

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Blacks/Hispanics with Heart Failure
Blacks/Hispanics with heart failure due to transthyretin cardiac amyloidosis will be identified by 99mTc-PYP scintigraphy. Those with transthyretin cardiac amyloidosis will be further subtyped into those with a genetic cause (ATTRm) and those with a non-genetic cause (ATTRwt - wild type transthyretin cardiac amyloidosis).
Drug: 99mTc-PYP
10 mCi of 99mTc-PYP will be administered intravenously and imaging will be performed after 1 hour.
Other Name: Technetium-99m-Pyrophosphate




Primary Outcome Measures :
  1. Prevalence of Transthyretin Cardiac Amyloidosis in Caribbean Hispanics and Blacks with heart failure (HF) [ Time Frame: 5 years ]
    The prevalence of ATTR CA will be defined by the number of cases with significant myocardial retention of Tc-99 PYP including both ATTRwt and ATTRm CA as a percentage of total enrollment.


Secondary Outcome Measures :
  1. Prevalence of ATTRwt and ATTRm in Blacks and Caribbean Hispanics [ Time Frame: 5 years ]
    Among subjects with ATTR-CA we will determine the prevalence of ATTRwt and ATTRm from the Val122Ile mutation in Blacks and Caribbean Hispanics

  2. Sex distribution of ATTR cardiac amyloidosis [ Time Frame: 5 years ]
    The prevalence of ATTR cardiac amyloidosis will be calculated among men and women enrolled in this study

  3. Disease progression in ATTRwt compared to ATTRm [ Time Frame: 5 years ]
    In the ATTR CA group alone, a composite time-to-first-event endpoint at 1-year of death, heart failure hospitalization, or 30% decline in 6-minute hall walk will be compared between ATTRwt and ATTRm subjects.

  4. RBP4 in Urine [ Time Frame: 5 years ]
    Retinol binding protein 4 (RBB4) will be measured in urine.


Biospecimen Retention:   Samples With DNA
Participants in this study will provide samples of blood and urine which will be analyzed for specific biomarkers and stored for possible future research.


Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Blacks and Caribbean Hispanics with heart failure not primarily due to ischemic heart disease or valvular disease.
Criteria

Inclusion Criteria:

  1. Black or Hispanic of Caribbean origin.
  2. Age ≥ 60 years.
  3. Diagnosis of heart failure, confirmed by one of two methods:

    1. Modified criteria utilized by Rich et al. which include a history of acute pulmonary edema or the occurrence of at least two of the following that improved with diuretic therapy without another identifiable cause: dyspnea on exertion, paroxysmal nocturnal dyspnea, orthopnea, bilateral lower extremity edema or exertional fatigue, and
    2. National Health and Nutrition Examination Survey (NHANES) congestive heart failure (CHF) criteria with a score ≥3.
  4. Able to understand and sign the informed consent document after the nature of the study has been fully explained.

Exclusion Criteria:

  1. Primary amyloidosis (AL) or secondary amyloidosis (AA).
  2. Prior liver or heart transplantation.
  3. Active malignancy or non-amyloid disease with expected survival of less than 1 year.
  4. Heart failure, in the opinion of the investigator, primarily caused by either valve disease or ischemic heart disease.

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): NCT03812172


Contacts
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Contact: Stephen Helmke 212-932-4537 sh2669@cumc.columbia.edu
Contact: Mathew S. Maurer, MD 212-305-9808 msm10@cumc.columbia.edu

Locations
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United States, Massachusetts
Boston Medical Center Not yet recruiting
Boston, Massachusetts, United States, 02118
Contact: Denise Fine, MD    617-638-8716      
Principal Investigator: Frederick L. Ruberg, MD         
United States, New York
Allen Hospital Not yet recruiting
New York, New York, United States, 10032
Contact: Stephen Helmke    212-932-4537    sh2669@cumc.columbia.edu   
Principal Investigator: Mathew S. Maurer, MD         
Harlem Hospital Not yet recruiting
New York, New York, United States, 10037
Contact: Damian C. Kurian, MD    212-939-1000      
Principal Investigator: Damian C. Kurian, MD         
Sponsors and Collaborators
Mathew Maurer
National Heart, Lung, and Blood Institute (NHLBI)
Boston Medical Center
Harlem Hospital Center
The Scripps Research Institute
Investigators
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Principal Investigator: Mathew S. Maurer, MD Columbia University
Principal Investigator: Frederick L Ruberg, MD Boston Medical Center/Boston University Medical Center

Publications of Results:

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Responsible Party: Mathew Maurer, Arnold and Arlene Goldstein Professor of Cardiology, Columbia University
ClinicalTrials.gov Identifier: NCT03812172     History of Changes
Other Study ID Numbers: AAAR1528
HL139671-01A1 ( Other Grant/Funding Number: NHLBI )
First Posted: January 23, 2019    Key Record Dates
Last Update Posted: March 28, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Mathew Maurer, Columbia University:
Heart Failure
Cardiac Amyloidosis
TTR mutation
Blacks
Hispanics
Aging

Additional relevant MeSH terms:
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Cardiomyopathies
Amyloidosis
Heart Diseases
Cardiovascular Diseases
Proteostasis Deficiencies
Metabolic Diseases