Empagliflozin as a Potential Therapeutic Solution for Patients With Brugada Syndrome

The goal of this clinical trial is to learn if Empagliflozin works to treat Brugada syndrome patients by affecting their electrocardiographic (ECG) patterns, and to evaluate its safety.

The main questions it aims to answer are:

• Does Empagliflozin improve specific electrocardiogram (ECG) patterns in Brugada syndrome patients, specifically by observing the change in J-point elevation recorded in V1 and V2 leads at the 4th, 3rd, and 2nd intercostal spaces (ICSs)? A responder is defined as a decrease in J-point elevation of ≥1 mm.
• What adverse events do participants experience when taking Empagliflozin, including hypotension, acute renal failure, hepatic injury, ketoacidosis, hypoglycemic events, urinary tract infections, genital infections, bone fractures, and events leading to lower limb amputation?

Researchers will compare each participant's ECG changes before and after three months of Empagliflozin treatment to assess its efficacy

Participants will:

• Take Empagliflozin once daily, starting at 10 mg. The dose will be increased to 25 mg at monthly follow-ups if participants are non-responders based on ECG ST-segment morphology. The total treatment period is three months.
• Visit the outpatient clinic monthly for three months of treatment to monitor efficacy and safety. The overall trial period, including screening, treatment, and follow-up, comprises five scheduled visits.

• Undergo a series of check-ups and tests, including:

  • 12-lead electrocardiography (ECG) recordings.
  • Monitoring and documentation of adverse events.
  • Blood and urine tests, such as complete blood count (CBC), liver function tests (AST/ALT), renal function tests (BUN/creatinine), electrolytes (sodium/potassium/calcium/magnesium/albumin), urinalysis, fasting glucose, HbA1c, and ketone measurements.

Study Overview

• Status: Not yet recruiting
• Conditions: Brugada Syndrome (BrS)
• Intervention / Treatment: Drug: Empagliflozin (EMPA)

Detailed Description

Inclusion Criteria

1. Patients diagnosed with Brugada syndrome and aged 18-99 years with spontaneous type 1 ECG, normal structural heart and patent coronary artery
2. Obtain written informed consent for participation in the clinical trial

Exclusion Criteria

1. Individuals with type 1 ECG pattern only observed with fever-induced or drug-induced were excluded from this exploratory study.
2. Current or prior use of an SGLT2 inhibitor within 12 weeks before screening or randomization
3. Known allergy or hypersensitivity to any SGLT2 inhibitor
4. History of ketoacidosis
5. Symptomatic hypotension or systolic blood pressure <90 mmHg or >180 mmHg
6. Heart failure
7. Acute myocardial infarction
8. ALT or AST >3× ULN at screening
9. Impaired renal function (eGFR <20 mL/min/1.73 m² [MDRD]), requiring dialysis, or functioning kidney transplant at screening
10. Pregnancy, nursing, or planning pregnancy during the trial
11. Enrollment in another investigational drug or device study or completion of such a study within the last 30 days
12. Known poor adherence to clinic visits or prescribed medications
13. Medical conditions that may limit trial participation, including severe respiratory disease, history of cancer with metastasis in the past four years (excluding non-melanoma skin cancer), or recent alcohol/substance misuse

Trial protocol The initial dose will start at 10 mg empagliflozin once a day, with monthly follow-ups for dose titration based on ECG ST-segment morphology done in lead V1, V2 at 4th, 3rd and 2nd intercostal spaces (ICSs). Responder is defined as any one of lead with a decrease in J-point elevation ≥1 mm from baseline. Responders will continue receiving 10 mg empagliflozin once a day, while non-responders will have their dose increased to 25 mg once a day.

This study followed a structured clinical trial protocol, including Screening, Treatment, and Follow-up periods. Participants underwent assessments at five scheduled visits corresponding to weeks -4 (screening), 4, 8, 12 (treatment phase), and 16 (follow-up). Peripheral blood mononuclear cell，(PBMC) will be collected and send to Stanford lab for Induced pluripotent stem cell (iPCS) once patient is enrolled in this study. Key evaluations included body weight (BW), automated office blood pressure (AOBP), and 12-lead electrocardiography (ECG). Safety monitoring encompassed adverse event documentation and laboratory tests with 15ml blood sample, including complete blood count (CBC), liver function tests (AST/ALT), renal function tests (BUN/creatinine), urinalysis, glucose AC, HbA1c, and ketone measurements. These assessments were conducted at predefined time points to ensure comprehensive monitoring of treatment effects and safety throughout the study duration.

Endpoints

Efficacy Endpoint Maximal change of type 1 Brugada ECG pattern recording with lead V1 and V2 in 4th, 3rd, and 2nd ICSs. Change of type 1 Brugada ECG pattern was defined as maximal J point elevation minus baseline J point elevation in the same leads. The responder is defined as decreased ≥ 1mm of J point in any one of above 6 leads.

Safety Endpoint Adverse event (AE) will be monitored as trail protocol. Adverse event including hypotension, symptomatic hypotension, acute renal failure, hepatic injury, ketoacidosis, hypoglycemic events, urinary tract infections, genital infections, bone fractures, events leading to lower limb amputation.

A serious adverse event (SAE) is any adverse event that results in death, is life-threatening, necessitates hospitalization or prolongation of existing hospitalization, causes significant disability or incapacity, leads to congenital anomalies or birth defects, or is deemed medically significant, potentially requiring intervention to prevent serious outcomes.

In accordance with the study protocol, the hospital will provide professional medical care and consultation in the event of adverse reactions or harm resulting from the clinical trial. Any adverse events will be reported to the Institutional Review Board (IRB) as required, with continuous monitoring of other participants' responses. All tests conducted are routine hospital examinations and pose no psychological harm to participants. Participant rights and protections will be upheld in accordance with the informed consent agreement.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: JYH-MING JIMMY JUANG, MD/PhD; Phone Number: +886-972651396; Email: jjmjuang@gmail.com
• Study Contact Backup: Name: HSINYU TSENG, MD; Phone Number: +886-972654628; Email: b97401042@gmail.com

Study Locations

• Taiwan
  • Taiwan
    • Taipei, Taiwan, Taiwan, 100
      • National Taiwan University Hospital
      • Contact: JYH-MING JIMMY JUANG, MD, PhD; Phone Number: +886972651396; Email: jjmjuang@gmail.com
      • Contact: HSINYU TSENG, MD; Phone Number: +886972654628; Email: b97401042@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients diagnosed with Brugada syndrome and aged 18-99 years with spontaneous type 1 ECG, normal structural heart and patent coronary artery
2. Obtain written informed consent for participation in the clinical trial

Exclusion Criteria:

1. Individuals with type 1 ECG pattern only observed with fever-induced or drug-induced were excluded from this exploratory study.
2. Current or prior use of an SGLT2 inhibitor within 12 weeks before screening or randomization
3. Known allergy or hypersensitivity to any SGLT2 inhibitor
4. History of ketoacidosis
5. Symptomatic hypotension or systolic blood pressure <90 mmHg or >180 mmHg
6. Heart failure
7. Acute myocardial infarction
8. ALT or AST >3× ULN at screening
9. Impaired renal function (eGFR <20 mL/min/1.73 m² [MDRD]), requiring dialysis, or functioning kidney transplant at screening
10. Pregnancy, nursing, or planning pregnancy during the trial
11. Enrollment in another investigational drug or device study or completion of such a study within the last 30 days
12. Known poor adherence to clinic visits or prescribed medications
13. Medical conditions that may limit trial participation, including severe respiratory disease, history of cancer with metastasis in the past four years (excluding non-melanoma skin cancer), or recent alcohol/substance misuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Empagliflozin	Drug: Empagliflozin (EMPA); Participants will take Empagliflozin once daily, starting at 10 mg. The dose will be increased to 25 mg at monthly follow-ups if participants are non-responders based on ECG ST-segment morphology. The total treatment period is three months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal change of type 1 Brugada pattern (defined as maximal J point deviation minus baseline J point hight) recording with 12-lead electrocardiogram within lead V1 and V2 in 4th, 3rd, and 2nd ICSs	Maximal Change of type 1 Brugada pattern (Coved ST segment elevation >2mm in >1 of V1-V3 followed by a negative T wave.) is defined as maximal J point deviation minus baseline J point elevation in the same leads. The responder is defined as decreased ≥ 1mm of J point in any one of above 6 leads.	From enrollment to the end of treatment at 8 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Related Adverse Events (Safety and Tolerability)	Adverse event (AE) will be monitored as trail protocol. Adverse event including hypotension, symptomatic hypotension, acute renal failure, hepatic injury, ketoacidosis, hypoglycemic events, urinary tract infections, genital infections, bone fractures, events leading to lower limb amputation.	From enrollment to the end of tial at 12 weeks

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Collaborators: Stanford University
• Investigators: Principal Investigator: Joseph Wu, MD, Phd, Stanford University; Principal Investigator: JYH-MING JIMMY JUANG, MD, PhD, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 15, 2025
• Primary Completion (Estimated): August 21, 2027
• Study Completion (Estimated): September 21, 2027

Study Registration Dates

• First Submitted: August 21, 2025
• First Submitted That Met QC Criteria: August 21, 2025
• First Posted (Estimated): August 28, 2025

Study Record Updates

• Last Update Posted (Estimated): September 12, 2025
• Last Update Submitted That Met QC Criteria: September 7, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Brugada Syndrome (BrS); Sodium-glucose cotransporter 2 inhibitors (SGLT-2i); Empaflifozin
• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Cardiovascular Diseases; Heart Diseases; Genetic Diseases, Inborn; Arrhythmias, Cardiac; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Brugada Syndrome; empagliflozin
• Other Study ID Numbers: 202506158MINB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No