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Prevalence and Prediction of ATTR in Ambulatory Patients With HFpEF (TTRinHFpEF)

Primary Purpose

Transthyretin Amyloidosis, Heart Failure, Heart Failure, Diastolic

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
99mTc-pyrophosphate Scintigraphy
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Transthyretin Amyloidosis focused on measuring Transthyretin Amyloidosis, Heart Failure, Heart Failure, Diastolic, Amyloidosis

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with a confirmed diagnosis of HFpEF.
  • Age ≥65 years old

Exclusion Criteria:

  • End stage chronic kidney disease on dialysis (CKD stage 5 as defined as eGFR <15mL/min)
  • no history of HFrEF (LVEF<40%) with the exception of low LVEF in the setting of acute decompensation, AF RVR, ACS/MI, etc
  • Negative 99mTc-pyrophosphate scan within a year
  • Unable to lie down for 15 minutes for the 99mTc-pyrophosphate scan
  • Known diagnosis of amyloidosis
  • Severe valvular heart disease that is uncorrected (moderate to severe is considered exclusionary)

Sites / Locations

  • Massachusetts General HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Patients 65 and older with Heart Failure with Preserved Ejection Fraction

Arm Description

Patients 65 years and older presenting to Massachusetts General Hospital with a known diagnosis of HFpEF and without a diagnosis of amyloidosis in the ambulatory (outpatient) setting will undergo a 99Tc-Pyrophosphate Scan to identify Cardiac Amyloidosis

Outcomes

Primary Outcome Measures

Diagnosis of 99mTc-pyrophosphate scan positive ATTR
A cardiac disease in which misfolded proteins aggregate into amyloid fibril and deposit interstitially, leading to diastolic dysfunction and heart failure

Secondary Outcome Measures

New York Heart Association function classification
Classifies the severity of a patients Heart Failure in terms of their limitations during physical activity
Impact of HF as assessed by Kansas City Cardiomyopathy Questionnaire
Kansas City Cardiomyopathy Questionnaire is a questionnaire that determines in the impact of Heart Failure on their health status, such as quality of life, symptoms, function, etc.)
Exercise capacity as determined by a 6-minute walk test
The 6 minute walk test is used to determine an objective measurement of a patients aerobic capacity and endurance

Full Information

First Posted
July 16, 2021
Last Updated
October 17, 2023
Sponsor
Massachusetts General Hospital
Collaborators
Akcea Therapeutics, Pfizer, Alnylam Pharmaceuticals, Eidos Therapeutics, a BridgeBio company
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1. Study Identification

Unique Protocol Identification Number
NCT05577819
Brief Title
Prevalence and Prediction of ATTR in Ambulatory Patients With HFpEF
Acronym
TTRinHFpEF
Official Title
Prevalence and Prediction of Transthyretin Amyloidosis in Ambulatory Patients With Heart Failure With Preserved Ejection Fraction
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 2, 2020 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
Akcea Therapeutics, Pfizer, Alnylam Pharmaceuticals, Eidos Therapeutics, a BridgeBio company

4. Oversight

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

5. Study Description

Brief Summary
Recent studies have shown that transthyretin amyloidosis (ATTR) can sometimes cause a type of heart failure where the pumping function of the heart is normal, also known as Heart Failure with Preserved Ejection Fraction (HFpEF) or diastolic heart failure. In this single center diagnostic study, we will evaluate for ATTR in patients with HFpEF in order to to determine how frequently this occurs and how we can predict which heart failure patients may have TTR amyloidosis. Our goal is to identify amyloidosis in heart failure patients earlier so that they can start treatment.
Detailed Description
Patients 65-years and older with HFpEF will be enrolled to participate in this single center, event driven (positive nuclear amyloid scan also known as 99mTc-pyrophosphate SPECT scan) study. During the single study visit the following will be obtained: 99mTc-pyrophosphate SPECT scan Blood and DNA (optional) sample collection Questionnaires in regards to neuropathy, carpal tunnel, frailty, and Heart failure symptoms and how they may affect ones quality of life 6-Minute Walk Test ECG (electrocardiogram) Echocardiogram Electronic health records will be reviewed for up to 5 years in order to determine hospitalization and survival of the study participants. Clinical outcomes of interest include a combined endpoint of days alive outside of the hospital from heart failure hospitalizations at one and five years, presence of autonomic neuropathy, presence of carpal tunnel syndrome, presence of polyneuropathy. Additionally, Individual clinical endpoints are also endpoints of interest. The results from this study will be used to determine how frequently heart failure patients have transthyretin amyloidosis in their heart and better understand their symptoms. We hope that better understanding transthyretin amyloidosis in heart failure patients will help us identify affected patients so that they can receive treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Transthyretin Amyloidosis, Heart Failure, Heart Failure, Diastolic, Amyloidosis
Keywords
Transthyretin Amyloidosis, Heart Failure, Heart Failure, Diastolic, Amyloidosis

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
515 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Patients 65 and older with Heart Failure with Preserved Ejection Fraction
Arm Type
Experimental
Arm Description
Patients 65 years and older presenting to Massachusetts General Hospital with a known diagnosis of HFpEF and without a diagnosis of amyloidosis in the ambulatory (outpatient) setting will undergo a 99Tc-Pyrophosphate Scan to identify Cardiac Amyloidosis
Intervention Type
Diagnostic Test
Intervention Name(s)
99mTc-pyrophosphate Scintigraphy
Other Intervention Name(s)
PYP Scan, Pyrophosphate Scan
Intervention Description
Cardiac Imaging Technique used to diagnose Transthyretin Cardiac Amyloidosis by use of 15 mCi of 99mTC-Pyrophosphate tracer
Primary Outcome Measure Information:
Title
Diagnosis of 99mTc-pyrophosphate scan positive ATTR
Description
A cardiac disease in which misfolded proteins aggregate into amyloid fibril and deposit interstitially, leading to diastolic dysfunction and heart failure
Time Frame
Day 1 (day of study visit)
Secondary Outcome Measure Information:
Title
New York Heart Association function classification
Description
Classifies the severity of a patients Heart Failure in terms of their limitations during physical activity
Time Frame
Day 1 (day of study visit)
Title
Impact of HF as assessed by Kansas City Cardiomyopathy Questionnaire
Description
Kansas City Cardiomyopathy Questionnaire is a questionnaire that determines in the impact of Heart Failure on their health status, such as quality of life, symptoms, function, etc.)
Time Frame
Day 1 (day of study visit)
Title
Exercise capacity as determined by a 6-minute walk test
Description
The 6 minute walk test is used to determine an objective measurement of a patients aerobic capacity and endurance
Time Frame
Day 1 (day of study visit)
Other Pre-specified Outcome Measures:
Title
Presence of autonomic neuropathy
Description
Medical records and phone follow-up with patients and/or their physicians will allow the investigators to ascertain vital status and any significant clinical events
Time Frame
Time from study Visit until the date of documented event up to 5 years after the study closure
Title
Presence of carpal tunnel syndrome
Description
Medical records and phone follow-up with patients and/or their physicians will allow the investigators to ascertain vital status and any significant clinical events
Time Frame
Time from study Visit until the date of documented event up to 5 years after the study closure
Title
Presence of polyneuropathy
Description
Medical records and phone follow-up with patients and/or their physicians will allow the investigators to ascertain vital status and any significant clinical events
Time Frame
Time from study Visit until the date of documented event up to 5 years after the study closure
Title
Combined endpoint of days alive outside of hospital from HF hospitalizations at one and five years
Description
Medical records and phone follow-up with patients and/or their physicians will allow the investigators to ascertain vital status and any significant clinical events
Time Frame
Time from study Visit until the date of documented event up to 5 years after the study closure
Title
Individual endpoints of all-cause mortality, cardiovascular mortality, all-cause hospitalizations, cardiovascular hospitalizations and HF hospitalizations.
Description
Medical records and phone follow-up with patients and/or their physicians will allow the investigators to ascertain vital status and any significant clinical events
Time Frame
Time from study Visit until the date of documented event up to 5 years after the study closure

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with a confirmed diagnosis of HFpEF. Age ≥65 years old Exclusion Criteria: End stage chronic kidney disease on dialysis (CKD stage 5 as defined as eGFR <15mL/min) no history of HFrEF (LVEF<40%) with the exception of low LVEF in the setting of acute decompensation, AF RVR, ACS/MI, etc Negative 99mTc-pyrophosphate scan within a year Unable to lie down for 15 minutes for the 99mTc-pyrophosphate scan Known diagnosis of amyloidosis Severe valvular heart disease that is uncorrected (moderate to severe is considered exclusionary)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jason Chen, BS
Phone
617-643-1695
Email
jchen134@mgh.harvard.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Laura Stockhausen, BS
Phone
617-724-1339
Email
lstockhausen@mgh.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hanna K Gaggin, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
NurAlima Grandison, BA
First Name & Middle Initial & Last Name & Degree
Hanna Gaggin, MD

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Prevalence and Prediction of ATTR in Ambulatory Patients With HFpEF

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