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

April 3, 2024 updated by: Mathew S. Maurer

Screening for Cardiac Amyloidosis With Nuclear Cardiology for Minority Populations

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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-HDP may be used in cases of interrupted supply of PYP) 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.

Study Type

Observational

Enrollment (Estimated)

800

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06519
        • Recruiting
        • Yale University/Yale New Haven Medical Center
        • Principal Investigator:
          • Ed Miller, MD, PhD
        • Contact:
          • Cinthia deFreitas, RN
          • Phone Number: 203-785-6315
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Recruiting
        • Boston Medical Center/Boston University Medical Center
        • Contact:
          • Denise Fine
          • Phone Number: 617-638-8716
        • Principal Investigator:
          • Frederick L. Ruberg, MD
    • New York
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Irving Medical Center
        • Contact:
        • Principal Investigator:
          • Mathew S. Maurer, MD
      • New York, New York, United States, 10037
        • Recruiting
        • Harlem Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Damian C. Kurian, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years and older (Adult, Older Adult)

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.

Description

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. Left ventricular septal OR inferolateral wall thickness ≥12 mm by echocardiography.
  5. Left ventricular Ejection fraction >30% by echocardiography.
  6. 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 severe left-sided valve disease. Note: if valve was repaired, subject may be considered as no longer with severe valve disease.Heart failure, in the opinion of the investigator, primarily caused by either valve disease or ischemic heart disease.
  5. Heart failure, in the opinion of the investigator, primarily caused by ischemic heart disease.
  6. Ventricular assist device or anticipated within the next 6 months.
  7. Impairment from stroke, injury or other medical disorder that precludes participation in the study.
  8. Disabling dementia or other mental or behavioral disease.
  9. Enrollment in a clinical trial not approved for co-enrollment.
  10. Expected use of continuous intravenous inotropic therapy in the next 6 months.
  11. High risk for non-adherence as determined by screening evaluation.
  12. Inability or unwillingness to comply with the study requirements.
  13. Chronic kidney disease with eGFR <15 mL/min/1.73 m2 or ESRD.
  14. Weight >350 lb.
  15. Nursing home resident.
  16. Other reason that would make the subject inappropriate for entry into this study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

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 (or 99mTc-HDP) 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 or 99m Tc-HDP
10-25 mCi of 99mTc-PYP (or 99m Tc-HDP) will be administered intravenously and imaging will be performed after 3 hours.
Other Names:
  • Technetium-99m-Pyrophosphate or Technetium-99m-HydroxyMethyleneDiphosphonate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
5 years

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mathew S. Maurer

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)
Yale University
Boston Medical Center
The Scripps Research Institute
Harlem Hospital Center

Investigators

  • Principal Investigator: Mathew S. Maurer, MD, Columbia University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 15, 2019

Primary Completion (Estimated)

June 1, 2024

Study Completion (Estimated)

June 1, 2024

Study Registration Dates

First Submitted

January 10, 2019

First Submitted That Met QC Criteria

January 17, 2019

First Posted (Actual)

January 23, 2019

Study Record Updates

Last Update Posted (Actual)

April 4, 2024

Last Update Submitted That Met QC Criteria

April 3, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AAAS4054
  • R01HL139671-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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