Sodium Glucose Co-transporter (SGLT) Inhibitors in Nonobstructive Hypertrophic Cardiomyopathy

Обзор

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: 1. Will sotagliflozin be well tolerated in patients with nonobstructive HCM? 2. Will sotaglifozin improve exercise capacity, diastolic dysfunction and/or physical functioning in patients with nonobstructive HCM? 3. 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.

Вмешательства

• Препарат Sotagliflozin
  Sotagliflozin or placebo will be administered to each participant in a cross over study design. Each participant will receive active drug and placebo with randomization of the order in which they receive them.

Первичные конечные точки

• Number of participants with treatment-related adverse events [Срок оценки: Through study completion, 28 weeks]
• Intracavitary obstruction [Срок оценки: Through study completion, 28 weeks]
• Cardiac rhythm [Срок оценки: Through study completion, 28 weeks]
• Maximal exercise capacity [Срок оценки: Through study completion, 28 weeks]
• Submaximal exercise capacity [Срок оценки: Through study completion, 28 weeks]

Вторичные конечные точки (9)

• Systolic function [Срок оценки: Through study completion, 28 weeks]
• Contractility [Срок оценки: Through study completion, 28 weeks]
• Diastolic function [Срок оценки: Through study completion, 28 weeks]
• Left ventricular hypertrophy [Срок оценки: Through study completion, 28 weeks]
• Symptom scores [Срок оценки: Through study completion, 28 weeks]
• Symptom scores and quality of life [Срок оценки: Through study completion, 28 weeks]
• Biomarkers [Срок оценки: Through study completion, 28 weeks]
• Circulating metabolites [Срок оценки: Through study completion, 28 weeks]
• Measurement of periods of activity and rest [Срок оценки: Through study completion, 28 weeks]

Критерии участия

Критерии включения

• 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 1.
• 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.

Критерии исключения

• 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
• Hemoglobin < 10 g/dL
• Estimated glomerular filtration rate (eGFR) < 25 mL/min/1.73m\^2, or unstable or rapidly progressing renal disease at the time of randomization
• Subject inability/unwillingness to exercise
• Greater than moderate left sided valvular disease (mitral regurgitation, aortic stenosis, aortic regurgitation), moderate or greater mitral stenosis, or severe right-sided valvular disease based on baseline echo at the time of enrollment
• Current angina due to clinically significant epicardial coronary disease, as per investigator judgment
• Acute coronary syndrome or coronary intervention within the past 2 months
• Primary pulmonary artery hypertension (WHO Group 1 Pulmonary Arterial Hypertension)
• Clinically significant lung disease as defined by: Chronic Obstructive Pulmonary Disease meeting Stage III or greater GOLD criteria (FEV1<50% predicted), treatment with oral steroids within the past 6 months for an exacerbation of obstructive lung disease, or current use of supplemental oxygen aside from nocturnal oxygen for the treatment of obstructive sleep apnea.
• Clinically-significant ischemia, as per investigator's judgement, on stress testing without either (1) subsequent revascularization, (2) an angiogram demonstrating the absence of clinically significant epicardial coronary artery disease, as per investigator judgment; (3) a follow-up 'negative' stress test, particularly when using a more specific technique (i.e., a negative perfusion imaging test following a 'positive' ECG stress test)
• Symptomatic bradycardia or second- or third-degree heart block, in the absence of a pacemaker
• Significant liver disease impacting synthetic function or volume control (ALT/AST > 3x ULN, Albumin < 3.0 g/dL)
• Severe right ventricular dysfunction on baseline echocardiogram
• Orthostatic blood pressure response to the transition from supine to standing (>20 mmHg reduction in systolic blood pressure 2-3 minutes after standing)
• Active participation in another study that utilizes an investigational agent (observational studies/registries allowed)
• Any condition that, in the opinion of the investigator, will interfere with the completion of the study. This may include comorbid or psychiatric conditions that may impede successful completion of the protocol, or logistical concerns (e.g. inability to travel to the exercise unit).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of Pennsylvania — Philadelphia

Идентификаторы

NCT: NCT06433050 · 855065 · R61HL164376

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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