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N-of-1 for Beta-Blockers in Cardiac Amyloidosis

Primary Purpose

Cardiac Amyloidosis, Heart Diseases

Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Beta blocker
Sponsored by
Weill Medical College of Cornell University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Cardiac Amyloidosis focused on measuring beta blocker, cardiac amyloidosis, HFpEF, deprescribing, heart failure

Eligibility Criteria

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

Inclusion Criteria:

  1. Ambulatory adults age ≥65 years with TTR-cardiac amyloidosis (confirmed by PYP scan or biopsy)
  2. Taking beta-blocker

Exclusion Criteria:

  1. Alternate causes of HFpEF Syndrome:

    1. Severe aortic stenosis and mitral stenosis
    2. Constrictive pericarditis
    3. High Output HF

  2. Other compelling indication beta-blocker

    1. Hypertrophic cardiomyopathy
    2. Angina symptoms
    3. Acute coronary syndrome, myocardial infraction or coronary artery bypass surgery in prior 3 years
    4. Atrial arrhythmia with hospitalization for rapid ventricular response, prior 1 year
    5. Sinus tachycardia >100 bpm, atrial arrhythmia with ventricular rate >90 beats per minute, systolic blood pressure >160 mmHg

  3. Clinical instability (N-of-1 trials are appropriate for stable conditions only)

    1. Decompensated heart failure
    2. Hospitalized in past 30 days
    3. Medication changes or procedures in prior 14 days that could confound observations, per PI discretion
  4. Estimated life expectancy <6 months
  5. Moderate-severe dementia or psychiatric disorder precluding informed consent
  6. Any condition that, in Principal Investigator's opinion, makes the patient unsuitable for study participation

Sites / Locations

  • Weill Cornell MedicineRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

On-Off Sequence

Arm Description

This arm will follow an On-Off sequence. This is the only arm in the study. Subjects will begin in the On phase (Period 1), maintaining their beta-blocker dosage as previously prescribed to the subjects by their physician. Subjects will then continue to the Off phase (Period 2) where they will down-titrate their beta-blocker by 50% each week until they are completely off the drug for a total of two weeks. At the end of Period 2, the subjects will have their End of Intervention visit in which they will determine if they would like to continue or discontinue their beta-blockers for the foreseeable future.

Outcomes

Primary Outcome Measures

The change in exercise capacity when on beta-blocker versus when off beta-blocker, as measured by peak oxygen consumption (VO2) during Cardiopulmonary Exercise Test (CPET).
To understand the changes in exercise capacity between the On and Off phase via a Peak oxygen consumption (VO2) Cardiopulmonary Exercise Test. Cardiopulmonary exercise testing (CPET) measures breath-by-breath oxygen production during symptom-limited exercise on a stationary bike or treadmill. This permits calculation of peak oxygen consumption (VO2). Percent predicted peak VO2 for body weight will also be calculated.
The change in patient-reported health status when on beta-blocker versus when off beta-blocker, as measured by Kansas City Cardiomyopathy Questionnaire (KCCQ-12).
The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a heart failure-specific health status survey. Questions are ranked on 5- to 7-point Likert scales, with higher scores indicating better health status.
The change in patient-reported quality of life when on beta-blocker versus when off beta-blocker, as measured by the EuroQol-5d Visual Analogue Scale.
The EuroQol-5D Visual Analogue System (EQ-5D VAS) indicates patient-perceived health on a vertical visual analogue scale. The scale ranges from 0, indicating poorest health, to 100, indicating best health.

Secondary Outcome Measures

Change in patient-reported quality of life when on beta-blocker, as measured by the Patient-Reported Outcome Measurement Information System-29 (PROMIS-29)
Patient-Reported Outcome Measurement Information System-29 (PROMIS-29) is a health-related quality of life survey, with questions from 6 domains: depression, anxiety, physical function, pain interference, sleep disturbance, and ability to engage in social roles and activities. Questions are ranked on a 5-point Likert scale, with higher scores at times indicating better quality of life, and at other times indicating poorer quality of life. There is a pain rating scale ranging from 0 to 10, with higher scores indicating higher pain level. Scores are reported for each domain, as well as for pain rating.

Full Information

First Posted
August 17, 2021
Last Updated
August 15, 2023
Sponsor
Weill Medical College of Cornell University
Collaborators
U.S. Deprescribing Research Network
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1. Study Identification

Unique Protocol Identification Number
NCT05019027
Brief Title
N-of-1 for Beta-Blockers in Cardiac Amyloidosis
Official Title
N-of-1 Trials to Promote Deprescribing in Older Adults With Transthyretin Cardiac Amyloidosis
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 2023 (Anticipated)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
September 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Weill Medical College of Cornell University
Collaborators
U.S. Deprescribing Research Network

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The study team will generate preliminary data on whether patients with cardiac amyloidosis feel better when their beta-blocker is stopped. To achieve this objective, 20 N-of-1 trials (on vs. off) will be conducted, and the study team will subsequently interview participants to better understand their outcomes. Each subject will participate in 2 periods lasting between up to 6 weeks each based on each patient's health profile. We will also engage stakeholders to understand the acceptability and feasibility of deprescribing N-of-1 trials. The N-of-1 trials will be iteratively refined in real-time based on feedback.
Detailed Description
The intervention is an unblinded NIH Stage I of Behavioral Intervention Development trial, using a single-arm crossover withdrawal/reversal design (On [A] vs. Off [B]) with 2 periods, each period lasting up to 6 weeks, allowing for down-titration and washout. During the On (A) period, subjects will be on their beta-blocker, previously prescribed to the subjects by their physician. During the Off (B) period, their beta-blockers will be down-titrated and subsequently discontinued; we will decrease the dose of beta-blocker by 50% every week regardless of which beta-blocker they are on, similar to an algorithm used in a prior deprescribing trial.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiac Amyloidosis, Heart Diseases
Keywords
beta blocker, cardiac amyloidosis, HFpEF, deprescribing, heart failure

7. Study Design

Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
On-Off Sequence
Arm Type
Other
Arm Description
This arm will follow an On-Off sequence. This is the only arm in the study. Subjects will begin in the On phase (Period 1), maintaining their beta-blocker dosage as previously prescribed to the subjects by their physician. Subjects will then continue to the Off phase (Period 2) where they will down-titrate their beta-blocker by 50% each week until they are completely off the drug for a total of two weeks. At the end of Period 2, the subjects will have their End of Intervention visit in which they will determine if they would like to continue or discontinue their beta-blockers for the foreseeable future.
Intervention Type
Drug
Intervention Name(s)
Beta blocker
Intervention Description
The intervention is a single-arm crossover withdrawal/reversal design (On vs Off) with 2 total periods, each period lasting between up to 6 weeks. During the On period, subjects will be on their beta blocker. During the Off period, their beta blockers will be down-titrated by 50% each week and will be subsequently discontinued. Other Names: acebutolol atenolol betaxolol bisoprolol carvedilol labetalol metoprolol succinate metoprolol tartrate nadolol nebivolol penbutolol pindolol propranolol sotalol
Primary Outcome Measure Information:
Title
The change in exercise capacity when on beta-blocker versus when off beta-blocker, as measured by peak oxygen consumption (VO2) during Cardiopulmonary Exercise Test (CPET).
Description
To understand the changes in exercise capacity between the On and Off phase via a Peak oxygen consumption (VO2) Cardiopulmonary Exercise Test. Cardiopulmonary exercise testing (CPET) measures breath-by-breath oxygen production during symptom-limited exercise on a stationary bike or treadmill. This permits calculation of peak oxygen consumption (VO2). Percent predicted peak VO2 for body weight will also be calculated.
Time Frame
End of Period 1 (Week 2, 3, 4, 5, or 6) and Period 2 (Week 8, 9, 10, 11, or 12)
Title
The change in patient-reported health status when on beta-blocker versus when off beta-blocker, as measured by Kansas City Cardiomyopathy Questionnaire (KCCQ-12).
Description
The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a heart failure-specific health status survey. Questions are ranked on 5- to 7-point Likert scales, with higher scores indicating better health status.
Time Frame
Baseline; Bi-weekly, End of Period 1 (Week 2, 3, 4, 5, or 6), End of Period 2 (Week 8, 9, 10, 11, or 12)
Title
The change in patient-reported quality of life when on beta-blocker versus when off beta-blocker, as measured by the EuroQol-5d Visual Analogue Scale.
Description
The EuroQol-5D Visual Analogue System (EQ-5D VAS) indicates patient-perceived health on a vertical visual analogue scale. The scale ranges from 0, indicating poorest health, to 100, indicating best health.
Time Frame
Baseline; End Period 1 (Weeks 2, 3, 4, 5, or 6), End of Period 2 (Weeks 8, 9, 10, 11, or 12)
Secondary Outcome Measure Information:
Title
Change in patient-reported quality of life when on beta-blocker, as measured by the Patient-Reported Outcome Measurement Information System-29 (PROMIS-29)
Description
Patient-Reported Outcome Measurement Information System-29 (PROMIS-29) is a health-related quality of life survey, with questions from 6 domains: depression, anxiety, physical function, pain interference, sleep disturbance, and ability to engage in social roles and activities. Questions are ranked on a 5-point Likert scale, with higher scores at times indicating better quality of life, and at other times indicating poorer quality of life. There is a pain rating scale ranging from 0 to 10, with higher scores indicating higher pain level. Scores are reported for each domain, as well as for pain rating.
Time Frame
Baseline; Weekly for up to 12 weeks; End of Period 1 (Week 2, 3, 4, 5, or 6), Period 2 (Week 8, 9, 10, 11, or 12)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Ambulatory adults age ≥65 years with TTR-cardiac amyloidosis (confirmed by PYP scan or biopsy) Taking beta-blocker Exclusion Criteria: Other compelling indication beta-blocker Angina symptoms Acute coronary syndrome, myocardial infarction or coronary artery bypass surgery in prior 3 years Atrial arrhythmia with hospitalization for rapid ventricular response, prior 1 year Sinus tachycardia >100 bpm, atrial arrhythmia with ventricular rate >90 beats per minute, systolic blood pressure >160 mmHg Clinical instability (N-of-1 trials are appropriate for stable conditions only) Decompensated heart failure Hospitalized in past 30 days Medication changes or procedures in the prior 14 days that could confound observations, per the Principal Investigator's discretion Estimated life expectancy <6 months Moderate-severe dementia or psychiatric disorder precluding informed consent Any condition that, in Principal Investigator's opinion, makes the patient unsuitable for study participation
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Princess Osma, BA
Phone
646-962-5910
Email
pro4001@med.cornell.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Kate Zarzuela, MD
Phone
646-962-5909
Email
kaz4004@med.cornell.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Parag Goyal, MD, MSc
Organizational Affiliation
Weill Medical College of Cornell University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Weill Cornell Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Princess Osma, BA
Phone
646-962-5910
Email
pro4001@med.cornell.edu
First Name & Middle Initial & Last Name & Degree
Kate Zarzuela, MD
Phone
646-962-5909
Email
kaz4004@med.cornell.edu
First Name & Middle Initial & Last Name & Degree
Parag Goyal, MD, MSc

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

N-of-1 for Beta-Blockers in Cardiac Amyloidosis

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