search
Back to results

Exercise Training in Transthyretin Cardiac Amyloidosis

Primary Purpose

Amyloid Cardiomyopathy, Transthyretin Cardiac Amyloidosis

Status
Not yet recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Exercise Training
Sponsored by
Brigham and Women's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Amyloid Cardiomyopathy

Eligibility Criteria

60 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Diagnosis and typing of ATTR-CM by endomyocardial biopsy or by Grade 2 or Grade 3 pyrophosphate (PYP) positivity (exception: nonamyloid control arm in aim 1). Diagnosis of heart failure, with prior or current need of diuretics and increased N-terminal prohormone B-natureitic peptide (BNP) (≥450 pg/ml). Peak VO2 <80% predicted, indicating impaired aerobic capacity (for aim 2 only). Taking tafamidis (for aim 2 only) Able to walk 4 meters (with or without the use of an assistive device) and independent with basic activities of daily living at the time of enrolment. Adequate clinical stability has been achieved in the judgment of the investigator to allow participation in study assessments and the intervention. Signed informed consent document indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study. Exclusion Criteria: Acute myocardial infarction (Note: given that cardiac biomarkers such as troponin are frequently elevated in ATTR-CM patients, the diagnosis of acute myocardial infarction should be based on clinical diagnosis, not biomarkers alone) >70% obstructive coronary artery disease Severe aortic valve stenosis Already actively participating in formal, facility-based cardiac exercise Already engaging in regular moderate to vigorous exercise conditioning defined as > 30 minutes per day, ≥ twice per week consistently during the previous 6 weeks Ventricular assist device Light chain amyloidosis or other form of non-ATTR amyloidosis Advanced chronic kidney disease defined as estimated glomerular filtration rate <20 mL/min/1.73m2 Any organ transplantation Terminal illness other than HF with life expectancy < 1 year Pacemaker or implantable cardioverter-defibrillato (ICD) with heart rate limits < expected heart rates for exercise and unable to be reprogrammed Neuropathy due to transthyretin (TTR) mutation Impairment from stroke, injury or other medical disorder that precludes participation in the intervention Abnormal cardiopulmonary exercise testing (CPET) finding that requires further investigation and management Dementia that precludes ability to participate in exercise and follow study protocols High risk for non-adherence as determined by screening evaluation Inability or unwillingness to comply with the study requirements

Sites / Locations

  • Brigham and Women's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intervention arm

Arm Description

Outcomes

Primary Outcome Measures

peak oxygen consumption (VO2)
CPET performed at baseline and 12-weeks, following the exercise intervention will be used to measure aerobic capacity, peak VO2. The change in peak VO2 from baseline to 12 weeks is the primary outcome measure. An increase of > 1.0 ml/kg/min is considered a clinically meaningful increase

Secondary Outcome Measures

Kansas City Cardiomyopathy Questionnaire
Kansas City Cardiomyopathy Questionnaire (KCCQ) is a quality of life questionnaire. This will be recorded at baseline, 4-weeks and 12-weeks. The change in KCCQ score from baseline to 12 weeks is a secondary outcome. KCCQ scores are scaled from 0 to 100; where 0 denotes the lowest reportable health status and 100 the highest. An increase of 5 points is considered a clinically meaningful increase.
Lower extremity function
The short physical performance battery (SPPB) is an assessment of lower extremity function. The change in SPPB score from baseline to 12 weeks is a secondary outcome. This is a scale of 0-12, where 0 denotes the worst performance and 12 the highest. An increase of 1 point is considered a clinically meaningful increase.

Full Information

First Posted
March 22, 2023
Last Updated
April 4, 2023
Sponsor
Brigham and Women's Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT05797857
Brief Title
Exercise Training in Transthyretin Cardiac Amyloidosis
Official Title
Personalized Exercise Training to Improve Functional Capacity in Transthyretin Cardiac Amyloidosis
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 1, 2023 (Anticipated)
Primary Completion Date
June 30, 2027 (Anticipated)
Study Completion Date
June 30, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital

4. Oversight

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

5. Study Description

Brief Summary
Transthyretin cardiac amyloidosis causes debilitating heart failure in older adults. The proposed research will develop a personalized exercise training program to improve functional capacity in patients on optimal treatment for transthyretin cardiac amyloidosis. This is a vital next step to improve functional capacity and quality of life of people suffering from transthyretin cardiac amyloidosis.
Detailed Description
Heart failure (HF) affects over 5 million adults over the age of 65. Cardiac transthyretin amyloidosis (ATTR-CM) is a cause of HF in ~10% of older adults and leads to significant morbidity and mortality. Exercise intolerance is traditionally attributed to cardiac dysfunction but the contribution of other systems to this has not been studied. Musculoskeletal involvement is common in ATTR-CM and occur 5-10 years prior to onset of HF. Tafamidis, a transthyretin stabilizer, is the only approved treatment for ATTR-CM. It slows disease progression, prolongs life, and reduces HF hospitalizations. However, it does not improve functional capacity- no therapeutic intervention has been shown to do so in ATTR-CM. The idea behind this project is that skeletal muscle dysfunction from amyloidosis and HF severely limits exercise capacity and, thus, quality of life in ATTR-CM, and that targeted exercise training will improve quality of life by improving skeletal muscle performance and aerobic capacity. Cardiopulmonary exercise testing (CPET) and the short physical performance battery (SBBP), including a leg extensor muscle power assessment will be used to achieve the following specific aims; 1) to compare skeletal muscle performance in ATTR-CM and non-amyloid HF; and 2) to determine improvements in aerobic capacity and quality of life due to 12 weeks of supervised exercise training in patients with ATTR-CM. To achieve the second aim, we will use a personalized exercise intervention.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyloid Cardiomyopathy, Transthyretin Cardiac Amyloidosis

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Intervention arm
Arm Type
Experimental
Intervention Type
Other
Intervention Name(s)
Exercise Training
Intervention Description
A supervised, personalized exercise training program, which will consist of two 60-minute exercise training sessions per week.
Primary Outcome Measure Information:
Title
peak oxygen consumption (VO2)
Description
CPET performed at baseline and 12-weeks, following the exercise intervention will be used to measure aerobic capacity, peak VO2. The change in peak VO2 from baseline to 12 weeks is the primary outcome measure. An increase of > 1.0 ml/kg/min is considered a clinically meaningful increase
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Kansas City Cardiomyopathy Questionnaire
Description
Kansas City Cardiomyopathy Questionnaire (KCCQ) is a quality of life questionnaire. This will be recorded at baseline, 4-weeks and 12-weeks. The change in KCCQ score from baseline to 12 weeks is a secondary outcome. KCCQ scores are scaled from 0 to 100; where 0 denotes the lowest reportable health status and 100 the highest. An increase of 5 points is considered a clinically meaningful increase.
Time Frame
12 weeks
Title
Lower extremity function
Description
The short physical performance battery (SPPB) is an assessment of lower extremity function. The change in SPPB score from baseline to 12 weeks is a secondary outcome. This is a scale of 0-12, where 0 denotes the worst performance and 12 the highest. An increase of 1 point is considered a clinically meaningful increase.
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis and typing of ATTR-CM by endomyocardial biopsy or by Grade 2 or Grade 3 pyrophosphate (PYP) positivity (exception: nonamyloid control arm in aim 1). Diagnosis of heart failure, with prior or current need of diuretics and increased N-terminal prohormone B-natureitic peptide (BNP) (≥450 pg/ml). Peak VO2 <80% predicted, indicating impaired aerobic capacity (for aim 2 only). Taking tafamidis (for aim 2 only) Able to walk 4 meters (with or without the use of an assistive device) and independent with basic activities of daily living at the time of enrolment. Adequate clinical stability has been achieved in the judgment of the investigator to allow participation in study assessments and the intervention. Signed informed consent document indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study. Exclusion Criteria: Acute myocardial infarction (Note: given that cardiac biomarkers such as troponin are frequently elevated in ATTR-CM patients, the diagnosis of acute myocardial infarction should be based on clinical diagnosis, not biomarkers alone) >70% obstructive coronary artery disease Severe aortic valve stenosis Already actively participating in formal, facility-based cardiac exercise Already engaging in regular moderate to vigorous exercise conditioning defined as > 30 minutes per day, ≥ twice per week consistently during the previous 6 weeks Ventricular assist device Light chain amyloidosis or other form of non-ATTR amyloidosis Advanced chronic kidney disease defined as estimated glomerular filtration rate <20 mL/min/1.73m2 Any organ transplantation Terminal illness other than HF with life expectancy < 1 year Pacemaker or implantable cardioverter-defibrillato (ICD) with heart rate limits < expected heart rates for exercise and unable to be reprogrammed Neuropathy due to transthyretin (TTR) mutation Impairment from stroke, injury or other medical disorder that precludes participation in the intervention Abnormal cardiopulmonary exercise testing (CPET) finding that requires further investigation and management Dementia that precludes ability to participate in exercise and follow study protocols High risk for non-adherence as determined by screening evaluation Inability or unwillingness to comply with the study requirements
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sarah Cuddy, MD
Phone
617-732-8410
Email
scuddy1@bwh.harvard.edu

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
A limited access dataset generated from this project will rapidly be made available to the broader community for distribution to outside researchers according to established Mass General Brigham and NHLBI procedures and in accordance with NIH policies. Exercise training plans developed as part of this proposal will be made available.

Learn more about this trial

Exercise Training in Transthyretin Cardiac Amyloidosis

We'll reach out to this number within 24 hrs