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

Heart Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05019027
• Other study ID #: 21-07023710
• Status: Recruiting
• Phase: Phase 4
• Start date: January 31, 2024
• Est. completion date: September 2025

Study information

• Verified date: March 2024
• Source: Weill Medical College of Cornell University
• Contact: Princess Osma, BA
• Phone: 646-962-5910
• Email: pro4001[@]med.cornell.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: September 2025
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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 beta-blocker

1. Angina symptoms

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. Sinus tachycardia >100 bpm, atrial arrhythmia with ventricular rate >90 beats per minute, systolic blood pressure >160 mmHg

2. 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 the prior 14 days that could confound observations, per the Principal Investigator's discretion

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

Related Conditions & MeSH terms

• Amyloidosis
• Cardiac Amyloidosis
• Heart Diseases

Intervention

Drug:
• 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 will be subsequently discontinued. Other Names: acebutolol atenolol betaxolol bisoprolol carvedilol labetalol metoprolol succinate metoprolol tartrate nadolol nebivolol penbutolol pindolol propranolol sotalol

Locations

Country	Name	City	State
United States	Weill Cornell Medicine	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	U.S. Deprescribing Research Network

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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; Bi-weekly, End of Period 1 (Week 2, 3, 4, 5, or 6), End of Period 2 (Week 8, 9, 10, 11, or 12)
Primary	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	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.	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)