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| Name | Class |
|---|---|
| American Heart Association | OTHER |
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The proposed studies will test this hypothesis by randomizing patients with AF to 2-HOBA or placebo 7 days prior to AF ablation to allow 2-HOBA to reach steady-state levels. We hypothesize that tissue injury from AF ablation causes a large release of ROS that react with lipids to generate IsoLGs (Figure 2). In the absence of 2-HOBA, IsoLGs will react within seconds to form IsoLG-macromolecule adducts in atrial tissue, promoting early recurrence of AF. In the presence of 2-HOBA, IsoLGs will rapidly react to form IsoLG-macromolecule adducts in atrial tissue, promoting early recurrence of AF. In the presence of 2-HOBA, IsoLG will preferentially bind to and therefore be inactivated by 2-HOBA thereby sparing injury to the atrial tissue caused by oxidative stress and its contribution to early recurrence of AF. Early recurrence of AF will be measured by ECGs that are recorded once per day by a smartwatch (Apple Watch, Apple Inc., Cupertino, CA) with additional ECGs recorded by the participant if they experience symptoms of AF, or if the smartwatch alerts the participant of a possible AF episode via its auto-detection AF monitoring algorithm. The Apple Watch's AF algorithm is based on sampling of heart rate and variability and will give an audible alarm if those parameters indicate a possible episode of AF. The smartwatch records a single-lead ECG if the participant touches the watch with their contralateral hand. The day and time of the episode is also stored by the smartwatch. At the end of the 28-day follow-up period, study personnel will review the stored ECGs. Blood will be drawn prior to ablation and on post-procedure Day 1 for measurement of IsoLG-adduct levels. DNA will be extracted to explore a pharmacogenomic interaction with haplotypes at the chromosome 4q25 AF risk locus, which: 1) is strongly associated with the development of AF and the early recurrence of AF after ablation27; and 2) has been reported to be a regulator of an anti-oxidant gene program in response to cardiac injury.
The proposed double-blind, randomized, placebo-controlled trial of 2-HOBA in patients undergoing AF ablation is designed to address the following Specific Aims:
Specific Aim 1: To test the hypothesis that treatment with 2-HOBA reduces early recurrence of AF (clinical endpoint)
Specific Aim 2: To test the hypothesis that treatment with 2-HOBA reduces circulating levels of IsoLG-adducts (biochemical endpoint)
Specific Aim 3: To explore the idea that genetic variation at the 4q25 (PITX2) AF susceptibility locus modulates the clinical and biochemical response to 2-HOBA
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 2-HOBA | Active Comparator | 2-Hydroxybenzylamine(2-HOBA) 250 mg three tabs TID (po) for seven days prior to ablation and 28 days post ablation. |
|
| Placebo | Placebo Comparator | Placebo- three tabs TID (po) for seven days prior to ablation and 28 days post-ablation |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 2-Hydroxybenzylamine | Drug | 2-HOBA (2-Hydroxybenzlamine) 750mg will be given TID seven days prior to ablation and 28 days post ablation. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients Atrial Fibrillation | Participants will wear a smartwatch linked to an iPhone to continually record heart rate, variability and detection of arrhythmias. Participants will record a daily ECG each morning upon waking via the watch. In addition, participants will be notified by the smartwatch of 1) detection of atrial fibrillation or atrial flutter, 2) persistent high HR (> 110 bpm) outside of exercise | Post-ablation through 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| The Change in IsoLG-adducts Levels From AF Pre-ablation to Post-procedure Day #1 | Circulating IsoLG adducts can be measured in the blood at different periods of time. | Pre-ablation and Post-procedure day #1 |
| Exploratory Secondary Outcome |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ben Shoemaker, MD | Vanderbilt University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vanderbilt University Medical | Nashville | Tennessee | 37232 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34454591 | Derived | O'Neill MJ, Yoneda ZT, Crawford DM, Ye F, Ao M, Pitchford LM, Rathmacher JA, Murray KT, Akers WS, Roden DM, Michaud GF, Shoemaker MB. 2-Hydroxybenzylamine (2-HOBA) to prevent early recurrence of atrial fibrillation after catheter ablation: protocol for a randomized controlled trial including detection of AF using a wearable device. Trials. 2021 Aug 28;22(1):576. doi: 10.1186/s13063-021-05553-6. |
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95 participants signed consent. 89 participants were randomized. 6 were withdrawn after enrollment and never randomized.
Eligible subjects will be identified through EPIC. The study team will approach the patient in person in Arrhythmia Clinic or by phone prior to AF ablation. Information describing the study, will be provided. The risks and benefits will be described along with potential treatment advances. Informed consent will be obtained with the option of phone consent with electronic signature.
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| ID | Title | Description |
|---|---|---|
| FG000 | 2-HOBA | 2-Hydroxybenzylamine(2-HOBA) 250 mg three tabs TID (po) for seven days prior to ablation and 28 days post ablation. 2-Hydroxybenzylamine: 2-HOBA (2-Hydroxybenzlamine) 750mg will be given TID seven days prior to ablation and 28 days post ablation. |
| FG001 | Placebo | Placebo- three tabs TID (po) for seven days prior to ablation and 28 days post-ablation Placebo: Placebo will be given TID for seven days prior to ablation and 28 days post ablation. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 2-HOBA | 2-Hydroxybenzylamine(2-HOBA) 250 mg three tabs TID (po) for seven days prior to ablation and 28 days post ablation. 2-Hydroxybenzylamine: 2-HOBA (2-Hydroxybenzlamine) 750mg will be given TID seven days prior to ablation and 28 days post ablation. |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Patients Atrial Fibrillation | Participants will wear a smartwatch linked to an iPhone to continually record heart rate, variability and detection of arrhythmias. Participants will record a daily ECG each morning upon waking via the watch. In addition, participants will be notified by the smartwatch of 1) detection of atrial fibrillation or atrial flutter, 2) persistent high HR (> 110 bpm) outside of exercise | Posted | Count of Participants | Participants | Post-ablation through 28 days |
|
First 28 days
Adverse event information was collected for any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, only if it was considered related to the participant's participation in the research. Adverse events were collected from the time the consent was signed through participant completion.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 2-HOBA | 2-Hydroxybenzylamine(2-HOBA) 250 mg three tabs TID (po) for seven days prior to ablation and 28 days post ablation. 2-Hydroxybenzylamine: 2-HOBA (2-Hydroxybenzlamine) 750mg will be given TID seven days prior to ablation and 28 days post ablation. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| nausea | Gastrointestinal disorders | Non-systematic Assessment | nausea |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| M.Benjamin Shoemaker,MD MSCI | Vanderbilt University Medical Center | 615-322-2318 | moore.b.shoemaker@vumc.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 2, 2021 | Oct 11, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D001281 | Atrial Fibrillation |
| ID | Term |
|---|---|
| D001145 | Arrhythmias, Cardiac |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| C032416 | 2-(aminomethyl)phenol |
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This will be a double-blind, randomized study. Eligible subjects will be randomized according to a permuted block scheme with a block size of balancing interval, varying randomly according to the outcome of a computer-generated random number. This ensures that the cumulative number of assignments to each treatment (2-HOBA or placebo) will be in balance after each block of assignments had been made. A statistician will design the randomization table and enable the randomization tool within REDCap. After a patient enrolls for the study, the study nurse will determine the treatment assignment using the randomization tool in REDCap.
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The participant, care provider and investigator will all be blinded to the assigned treatment arm.
| Placebo | Other | Placebo will be given TID for seven days prior to ablation and 28 days post ablation. |
|
AF burden obtained from smartwatch as defined by the percentage of time in AF compared to the time the smartwatch was worn.
| 28 days post ablation |
Placebo- three tabs TID (po) for seven days prior to ablation and 28 days post-ablation Placebo: Placebo will be given TID for seven days prior to ablation and 28 days post ablation. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Inter-Quartile Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Placebo- three tabs TID (po) for seven days prior to ablation and 28 days post-ablation Placebo: Placebo will be given TID for seven days prior to ablation and 28 days post ablation. |
|
|
| Secondary | The Change in IsoLG-adducts Levels From AF Pre-ablation to Post-procedure Day #1 | Circulating IsoLG adducts can be measured in the blood at different periods of time. | This outcome required blood draw collections 1 day post ablation. During the Covid pandemic, this became impractical on approx. half the patients. IsoLG levels were only collected and analyzed on patients for whom blood samples were available. | Posted | Median | Inter-Quartile Range | percentage of IsoLG in circ. monocytes | Pre-ablation and Post-procedure day #1 |
|
|
|
| Secondary | Exploratory Secondary Outcome | AF burden obtained from smartwatch as defined by the percentage of time in AF compared to the time the smartwatch was worn. | The Apple Watch tracings were available to adjudicate recurrence in the final study cohort. However, burden required more data collection. Two of the participants were unable to provide the data. 1 participant refused. Outcome measure three part B required blood draw collections 1 day post ablation. During the Covid pandemic, this became impractical on ~half the patients. Outcome measure B (isoLG levels) were only collected and analyzed on patients for whom blood samples were available | Posted | Median | Inter-Quartile Range | percentage of time in AF | 28 days post ablation |
|
|
|
| 0 |
| 43 |
| 0 |
| 43 |
| 3 |
| 43 |
| EG001 | Placebo | Placebo- three tabs TID (po) for seven days prior to ablation and 28 days post-ablation Placebo: Placebo will be given TID for seven days prior to ablation and 28 days post ablation. | 0 | 39 | 0 | 39 | 7 | 39 |
| Headache | Nervous system disorders | Non-systematic Assessment | headache |
|
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| D013568 |
| Pathological Conditions, Signs and Symptoms |