A Phase 2 Double-blind Randomised Controlled Trial Studying the Effect of Sotagliflozin Versus Placebo in Individuals With Heart Failure and Type 1 Diabetes.

01-50-23

People with type 1 diabetes sometimes develop heart failure which can cause symptoms like breathlessness, tiredness or ankle swelling, reduced quality of life and lead to being admitted to hospital or suffering potential fatal consequences. This trial is investigating if a tablet called sotagliflozin, can improve quality of life in people with type 1 diabetes and heart failure. In addition, this trial will also assess the safety and tolerability of sotagliflozin in this population. In previous trials that included people with type 2 diabetes and heart failure sotagliflozin was shown to improve patients' symptoms of heart failure, quality of life and reduce the chance of people with heart failure being admitted to hospital or dying. However, people with type 1 diabetes and heart failure were not included in these trials meaning that it is not known if these benefits also apply to this population. This trial aims to recruit 320 people with type 1 diabetes and heart failure symptoms in multiple sites in the United Kingdom (UK). This trial will compare the health and quality of life of participants who take sotagliflozin tablets with participants who take placebo tablets, which is a dummy tablet that looks the same as sotagliflozin. Participants will be randomly allocated to one of two groups (i.e. one taking sotagliflozin and the other the placebo) and both the medical team and participants will not know in which group each participant is until the end of the study. Participants will be in the trial for approximately 6 months and will be given sotagliflozin or placebo tablets to take 1 per day for 4 months. The trial is expected to run for a total of 26 months.

2024-07-01

2026-06-01

2026-06-01

Not yet recruiting

Early phase I

320

Inclusion Criteria: * Age 18 years to \<85 years. * Type 1 diabetes. * Insulin dose ≥0.5 units/kg body weight at screening or body mass index (BMI) ≥25kg/m2 at screening * Using continuous glucose monitor at screening or willing to use one for the duration of the trial. * Diagnosis of heart failure (HF) regardless of left ventricular ejection fraction (LVEF), defined as one or more of the following: Previous HF hospitalisation where HF was documented as the primary cause of hospitalisation and there was a requirement for loop diuretics OR Impaired left ventricular (LV) function (i.e. LVEF \<50% by any imaging modality) at any time OR Preserved LV systolic function (LVEF ≥50%) with left atrial enlargement (2-dimensional echocardiographic measurement of left atrial width ≥3.8cm or left atrial length ≥5.0 cm or left atrial area ≥20cm2 or left atrial volume index \>29 ml/m2) within the last 24 months. OR Preserved LV systolic function (LVEF ≥50%) with left ventricular hypertrophy (2-dimensional echocardiographic measurement of end-diastolic interventricular septal diameter ≥1.2cm or end-diastolic left ventricular posterior wall diameter ≥1.2cm) within the last 24 months. OR Preserved LV systolic function (LVEF ≥50%) with echocardiographic diastolic dysfunction (septal e' \<7cm/sec or lateral e' \<10cm/sec or average E/e' ≥15) within the last 24 months. * New York Heart Association Class II-IV at screening. * Elevated N-terminal pro-B-type natriuretic peptide (≥250 ng/L for those in sinus rhythm, ≥400 ng/L if in atrial fibrillation) or B-type natriuretic peptide (≥75 ng/L for those in sinus rhythm, ≥100 ng/L if in atrial fibrillation) within 12 months of screening. * Kansas City Cardiomyopathy clinical summary score \<85 at screening. Exclusion Criteria: * Cardiac surgery (coronary artery bypass graft or valve replacement), type 1 myocardial infarction, implantation of cardiac device (including biventricular pacemaker) or cardiac mechanical support implantation within 1 month of screening, or between screening and randomisation, or planned during the trial. * End-stage heart failure requiring left ventricular assist devices, intra-aortic balloon pump, or any type of mechanical support at the time of randomisation. * Documented primary severe valvular heart disease, amyloidosis or hypertrophic cardiomyopathy as principal cause of heart failure as judged by the local investigator. * Respiratory disease thought to be the primary cause of dyspnoea as assessed by the local investigator. * Chronic kidney disease with estimated glomerular filtration rate \<25ml/min/1.73m2 at screening. * Moderate or severe hepatic impairment (e.g. Child-Pugh B and C) at screening as judged by the local investigator. * Use of sotagliflozin or any sodium-glucose co-transporter-2 inhibitors (SGLT2i) within 1 month of screening or between screening and randomisation. * Previous hypersensitivity/intolerance to SGLT2i. * Presence of malignancy with expected life expectancy \<1 year at screening. * Severe hypoglycaemia (hospitalisation for hypoglycaemia or episode requiring external assistance to treat) within 1 month prior to screening or between screening and randomisation. * One episode of diabetic ketoacidosis or nonketotic hyperosmolar state within 1 month of screening or between screening and randomisation, or ≥2 diabetic ketoacidosis or nonketotic hyperosmolar state events within 6 months of screening. * Pregnant or lactating women. * Women of childbearing age or male partners of women of childbearing age and not practicing an acceptable method of birth control * On a ketogenic diet. * Unwilling/unable to share glucose and ketone monitoring data. * Unwilling to wear continuous glucose monitoring during the trial. * Use of any investigational drugs within five times of the elimination half-life after the last dose or within 30 days, whichever is longer. Current enrolment in non-interventional, observational studies will be allowed.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 320, 'type': 'ESTIMATED'}}

2024-05-30