Cardiac AmyloidosisPhase 4NCT05019027
N-of-1 for Beta-Blockers in Cardiac Amyloidosis
A Phase 4 study testing Beta blocker in people with Cardiac Amyloidosis and Heart Diseases, run by Weill Medical College of Cornell University at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Cardiac Amyloidosis, Heart Diseases, TTR Cardiac Amyloidosis
- What is being tested?
- Beta blocker
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Jan 2024to 4 Jun 2026
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Ambulatory adults age ≥65 years with TTR-cardiac amyloidosis (confirmed by PYP scan or biopsy)
- Taking beta-blocker
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: N-of-1 Trials to Promote Deprescribing in Older Adults With Transthyretin 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.
Read the 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
- Being tested
- Beta blocker
- Keywords
- beta blocker, cardiac amyloidosis, HFpEF, deprescribing, heart failure
- Medical subject headings
- Amyloid Neuropathies, Familial, Heart Diseases, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Beta blockerDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Beta blocker |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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)
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.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2021
- Study start31 Jan 2024
- Primary completion4 Jun 2026
- Study completion4 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiac AmyloidosisStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Collaborators
- U.S. Deprescribing Research Network, National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Parag Goyal, MD, MSc, Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05019027
- Sponsor's protocol ID
- 21-07023710
- Other IDs
- R24AG064025
- Status last verified
- Jul 2026
- First submitted
- 17 Aug 2021
- Last updated
- 29 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- N-of-1 Trials to Promote Deprescribing in Older Adults With Transthyretin Cardiac Amyloidosis
- ClinicalTrials.gov ID
- NCT05019027
- Acronym / sponsor ID
- 21-07023710
- Conditions
- Cardiac Amyloidosis, Heart Diseases, TTR Cardiac Amyloidosis
- Keywords
- beta blocker, cardiac amyloidosis, HFpEF, deprescribing, heart failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Collaborators
- U.S. Deprescribing Research Network, National Institute on Aging (NIA)
- Study start
- 31 Jan 2024 (actual)
- Primary completion
- 4 Jun 2026 (actual)
- Study completion
- 4 Jun 2026 (actual)
- First posted
- 24 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| On-Off Sequence | Other | Drug: Beta blockerThis 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. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (2 listed)
- Ambulatory adults age ≥65 years with TTR-cardiac amyloidosis (confirmed by PYP scan or biopsy)
- Taking beta-blocker
Key exclusion criteria (19 listed)
- Other compelling indication(s) for beta-blockers:
- Clinical instability (N-of-1 trials are appropriate for stable conditions only)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Beta blockerThe 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 | Drug | On-Off Sequence |
Primary outcome
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.
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.
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.
1 secondary outcome
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Parag Goyal, MD, MSc principal investigator
Weill Medical College of Cornell University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Beta blocker in people with Cardiac Amyloidosis and Heart Diseases, run by Weill Medical College of Cornell University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2026.