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

NCT05019027 | Enrolling By Invitation Phase 4 DMC FDA Drug

• 1 other identifier: 21-07023710
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Cardiac Amyloidosis; Heart Diseases; TTR Cardiac Amyloidosis

Keywords

beta blocker; cardiac amyloidosis; HFpEF; deprescribing; heart failure

Outcome Measures

Primary Outcomes (3)

• 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.

  End of Period 1 (Week 2, 3, 4, 5, or 6) and Period 2 (Week 8, 9, 10, 11, or 12)

• 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.

  Baseline, End of Period 1 (Week 2, 3, 4, 5, or 6), End of Period 2 (Week 8, 9, 10, 11, or 12)

• 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.

  Baseline; End Period 1 (Weeks 2, 3, 4, 5, or 6), End of Period 2 (Weeks 8, 9, 10, 11, or 12)

Secondary Outcomes (1)

• Change in patient-reported quality of life when on beta-blocker, as measured by the Patient-Reported Outcome Measurement Information System-29 (PROMIS-29)

  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)

Study Arms (1)

On-Off Sequence

OTHER

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), where they will be on their beta-blocker (or the highest dose they can safely tolerate) 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 (or the lowest dose they can safely tolerate) for a total of two weeks. At the end of Period 2, the subjects will have their End of Intervention visit to determine if they would like to continue or discontinue their beta-blockers for the foreseeable future.

Drug: Beta blocker

Interventions

Beta blocker DRUG

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 until subsequently discontinued (or the lowest dose the subject can safely tolerate). Other Names: * acebutolol * atenolol * betaxolol * bisoprolol * carvedilol * labetalol * metoprolol succinate * metoprolol tartrate * nadolol * nebivolol * penbutolol * pindolol * propranolol

On-Off Sequence

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Other compelling indication(s) for beta-blockers:
• Angina
• 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
• Heart rate \>100 bpm within the prior 3 months
• Atrial arrhythmia with ventricular rate \>90 beats per minute within the prior 3 months
• Systolic blood pressure readings \>160 mmHg within the prior 1 month, unless classified as white coat hypertension/effect (e.g., migraine prevention, anxiety symptom management, hyperthyroidism, essential tumor reduction)
• Clinical instability (N-of-1 trials are appropriate for stable conditions only)
• Decompensated heart failure
• Hospitalized in the past 30 days
• Medication changes or procedures in the prior 14 days that could confound observations/data at Principal Investigator discretion
• Anticipated medication changes or procedures in subsequent 3 months that could confound observations/data at PI discretion
• Clinical instability from other medical issues
• Estimated life expectancy \<6 months
• Moderate-severe dementia or psychiatric disorder precluding informed consent

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• U.S. Deprescribing Research Network: collaborator

Study Sites (1)

Weill Cornell Medicine

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Amyloid Neuropathies, Familial; Heart Diseases; Heart Failure

Interventions

Adrenergic beta-Antagonists

Condition Hierarchy (Ancestors)

Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Amyloid Neuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amyloidosis, Familial; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Amyloidosis; Proteostasis Deficiencies; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs

Study Officials

• Parag Goyal, MD, MSc

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2021
• First Posted: August 24, 2021
• Study Start: January 31, 2024
• Primary Completion: March 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: October 23, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)