2-Hydroxybenzylamine (2-HOBA) to Prevent Early Recurrence of Atrial Fibrillation After Catheter-based Ablation

NCT04433091 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 192520
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Atrial Fibrillation

Keywords

Ablation

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• The Change in IsoLG-adducts Levels From AF Pre-ablation to Post-procedure Day #1

  Pre-ablation and Post-procedure day #1

• Exploratory Secondary Outcome

  28 days post ablation

Study Arms (2)

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.

Drug: 2-Hydroxybenzylamine

Placebo

PLACEBO COMPARATOR

Placebo- three tabs TID (po) for seven days prior to ablation and 28 days post-ablation

Other: Placebo

Interventions

2-Hydroxybenzylamine DRUG

2-HOBA (2-Hydroxybenzlamine) 750mg will be given TID seven days prior to ablation and 28 days post ablation.

Also known as: 2- HOBA

2-HOBA

Placebo OTHER

Placebo will be given TID for seven days prior to ablation and 28 days post ablation.

Placebo

Eligibility Criteria

• Age: 22 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• First time AF ablation with radiofrequency or cryo ablation
• Repeat AF ablation if the patient has persistent AF and ablation of non-pulmonary vein substrate is planned (e.g. posterior wall ablation, mitral or roof line, etc)
• Able to provide written, informed consent
• years of age or older

You may not qualify if:

• Planned surgical or hybrid (surgical + catheter) ablation
• Amiodarone within past 3 months
• Use of oral steroids or colchicine
• Pro-inflammatory, rheumatologic disorder (e.g. RA, SLE, IBD, psoriasis, ankylosing spondylitis)
• NYHA Class III/IV Heart Failure
• LVEF \<35%
• Active ischemia
• Hypertrophic Cardiomyopathy
• Cardiac or thoracic surgery within 6 months
• Expected life span \< 1 year
• Creatinine clearance \<30 ml/min
• Prior or planned heart transplantation
• Pregnant women
• Aspirin allergy
• Current use of MAO-I

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• American Heart Association: collaborator

Study Sites (1)

Vanderbilt University Medical

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• 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.

  PMID: 34454591 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

2-(aminomethyl)phenol

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: M.Benjamin Shoemaker,MD MSCI
• Organization: Vanderbilt University Medical Center

moore.b.shoemaker@vumc.org

615-322-2318

Study Officials

• Ben Shoemaker, MD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The participant, care provider and investigator will all be blinded to the assigned treatment arm.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc Professor

Model Details: 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.

Study Record Dates

• First Submitted: June 3, 2020
• First Posted: June 16, 2020
• Study Start: May 15, 2020
• Primary Completion: January 30, 2022
• Study Completion: January 30, 2023
• Last Updated: November 21, 2024
• Results First Posted: November 21, 2024

Record last verified: 2024-11

Locations

US (1)