Sodium Glucose Co-transporter (SGLT) Inhibitors in Nonobstructive Hypertrophic Cardiomyopathy
Overview
- Phase
- Early Phase 1
- Intervention
- Sotagliflozin
- Conditions
- Hypertrophic Cardiomyopathy Without Obstruction
- Sponsor
- University of Pennsylvania
- Enrollment
- 26
- Locations
- 1
- Primary Endpoint
- Maximal exercise capacity
- Status
- Recruiting
- Last Updated
- 2 months ago
Overview
Brief Summary
The goal of this clinical trial is to learn if sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, works to treat symptomatic, nonobstructive hypertrophic cardiomyopathy (noHCM) in adult patients. It will also learn about the safety of sotagliflozin in this patient population. The main questions it aims to answer are:
- Will sotagliflozin be well tolerated in patients with nonobstructive HCM?
- Will sotaglifozin improve exercise capacity, diastolic dysfunction and/or physical functioning in patients with nonobstructive HCM?
- Will sotagliflozin improve circulating markers of cardiac metabolism in patients with nonobstructive HCM?
Researchers will compare sotagliflozin to a placebo (a look-alike substance that contains no drug) to see if sotagliflozin is effective at treating hypertrophic cardiomyopathy (HCM).
Participants will:
Take sotagliflozin or a placebo every day for 12 weeks. They will then cross-over (or switch) to taking placebo or sotagliflozin (whichever one they did not take initially) for an additional 12 weeks.
Visit the clinic once every 4-12 weeks for checkups, surveys, and tests including a stress test and echocardiogram.
Investigators
Sharlene Day
Associate Professor of Cardiovascular Medicine
University of Pennsylvania
Eligibility Criteria
Inclusion Criteria
- •Age at least 18 years, both sexes
- •Provision of signed and dated informed consent form
- •Stated willingness to comply with all study procedures and availability for the duration of the study
- •Ability to take oral medication and be willing to adhere to the study intervention.
- •For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 2 weeks after the end of administration of study drug.
- •Diagnosis of HCM with NYHA Class II-III functional class or New York Heart Association (NYHA) Class I with peak VO2 \< 90% on cardiopulmonary exercise stress testing performed at Visit
- •Left ventricular outflow tract gradient \< 50 mmHg at rest, with valsalva, and with exercise.
- •7\. Left ventricular ejection fraction \> 50% by echocardiogram or cardiac MRI based on the most recent assessment in the past year prior to screening and confirmed during Visit 1 echocardiogram.
- •8\. Stable medical therapy for at least 1 month prior to study enrollment.
Exclusion Criteria
- •Receiving therapy with an SGLT2 inhibitor within 8 weeks prior to enrollment or previous intolerance of an SGLT2 inhibitor
- •Type 1 diabetes mellitus
- •Age \<18 years old
- •Pregnant or lactating women: Women of childbearing potential will undergo a urine pregnancy test during the screening visit.
- •Uncontrolled atrial fibrillation, as defined by a resting heart rate \> 100 beats per minute at the time of the baseline assessment
- •Paroxysmal atrial fibrillation (Afib) or flutter with plans to attempt to restore sinus rhythm (with drug therapy, ablation, or DC cardioversion) during the study period.
- •Unable to attain a respiratory exchange ratio of at least 1.05 on cardiopulmonary exercise test (CPET) on the day of screening.
- •Septal reduction therapy within the previous 3 months.
- •Implantable cardio-defibrillator (ICD) implantation planned during the study period.
- •Implantation of a cardiac resynchronization therapy (CRT) device within 12 weeks prior to enrollment or intent to implant a CRT device during the study period
Arms & Interventions
Placebo first phase, Sotagliflozin second phase
Matching placebo once daily will be administered in the first phase, Sotagliflozin 400 mg once daily will be administered in the second phase
Intervention: Sotagliflozin
Sotagliflozin first phase, Placebo second phase
Sotagliflozin 400 mg once daily will be administered in the first phase, matching placebo once daily will be administered in the second phase
Intervention: Sotagliflozin
Outcomes
Primary Outcomes
Maximal exercise capacity
Time Frame: Through study completion, 28 weeks
Peak oxygen consumption in mL/min
Intracavitary obstruction
Time Frame: Through study completion, 28 weeks
Intracavitary left ventricular pressure gradient in mmHg
Cardiac rhythm
Time Frame: Through study completion, 28 weeks
New occurrence of cardiac arrhythmia measured by ambulatory monitoring
Number of participants with treatment-related adverse events
Time Frame: Through study completion, 28 weeks
Adverse event reporting
Submaximal exercise capacity
Time Frame: Through study completion, 28 weeks
Stroke volume augmentation at exercise steady state in mL/min
Secondary Outcomes
- Left ventricular hypertrophy(Through study completion, 28 weeks)
- Diastolic function(Through study completion, 28 weeks)
- Symptom scores and quality of life(Through study completion, 28 weeks)
- Measurement of periods of activity and rest(Through study completion, 28 weeks)
- Systolic function(Through study completion, 28 weeks)
- Symptom scores(Through study completion, 28 weeks)
- Biomarkers(Through study completion, 28 weeks)
- Circulating metabolites(Through study completion, 28 weeks)
- Contractility(Through study completion, 28 weeks)