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Enrolling by Invitation

NCT Number: NCT05019027

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

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.

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Key information

Conditions

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

Age range

65 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Weill Cornell Medicine

New York, 10065, United States

About this study

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, participants will be on their beta-blocker (or the highest dose they can safely tolerate), as previously prescribed to the subjects by their physician. During the Off (B) period, their beta-blockers will be down-titrated and subsequently discontinued (or at the lowest dose they can safely tolerate); 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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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(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
  • Language barrier that will preclude informed consent and ability to comprehend study procedures
  • Non-compliance or inability to complete study procedures
  • Enrollment in a clinical trial not approved for co-enrollment
  • Any condition that, in Principal Investigator or treating physician's opinion, makes the patient unsuitable for study participation

Treatment and study plan

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

Primary outcomes

  1. 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).

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

    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.

  2. 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).

    Time frame: Baseline, End of Period 1 (Week 2, 3, 4, 5, or 6), End of Period 2 (Week 8, 9, 10, 11, or 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.

  3. 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.

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

    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 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)

    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)

    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.

Sponsors and collaborators

Lead sponsor

Weill Medical College of Cornell University

Other

Collaborators

  • U.S. Deprescribing Research Network

Registry information

Official study title

N-of-1 Trials to Promote Deprescribing in Older Adults With Transthyretin Cardiac Amyloidosis

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Aug 24, 2021
Registry last updated
Oct 23, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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