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

NCT ID: NCT05019027

Last Updated: 2025-10-23

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-31
• Study Completion Date: 2026-12-31

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, 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.

Conditions

Cardiac Amyloidosis; Heart Diseases; TTR Cardiac Amyloidosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

On-Off Sequence

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.

Group Type: OTHER

Beta blocker

Intervention Type: 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

Interventions

Beta blocker

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

Intervention Type: DRUG

Eligibility Criteria

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. Other compelling indication(s) for beta-blockers:

1. Angina

2. Acute coronary syndrome, myocardial infarction or coronary artery bypass surgery in prior 3 years

3. Atrial arrhythmia with hospitalization for rapid ventricular response, prior 1 year

4. Heart rate >100 bpm within the prior 3 months

5. Atrial arrhythmia with ventricular rate >90 beats per minute within the prior 3 months

6. 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)

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

1. Decompensated heart failure

2. Hospitalized in the past 30 days

3. Medication changes or procedures in the prior 14 days that could confound observations/data at Principal Investigator discretion

4. Anticipated medication changes or procedures in subsequent 3 months that could confound observations/data at PI discretion

5. Clinical instability from other medical issues

3. Estimated life expectancy <6 months

4. Moderate-severe dementia or psychiatric disorder precluding informed consent

5. Language barrier that will preclude informed consent and ability to comprehend study procedures

6. Non-compliance or inability to complete study procedures

7. Enrollment in a clinical trial not approved for co-enrollment

8. Any condition that, in Principal Investigator or treating physician's opinion, makes the patient unsuitable for study participation

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

U.S. Deprescribing Research Network

UNKNOWN

Sponsor Role: collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Parag Goyal, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

Weill Cornell Medicine

New York, New York, United States

Countries

United States

Other Identifiers

21-07023710

Identifier Type: -

Identifier Source: org_study_id