Type 1 Diabetes, Heart Failure Nutritional, Metabolic, Endocrine
Conditions
Interventions
Participants will be randomised using an Interactive Web-based Randomisation System to one of two groups: active vs placebo 1:1
Active arm: Sotagliflozin 200 mg oral tablets once per day for 16 weeks
Sponsors
University of Dundee
Eligibility
Sex/Gender
All
Age
18 Years to 85 Years
Inclusion criteria
Inclusion criteria: Current key inclusion criteria as of 11/05/2026: 1. Age 18 years to 29 ml/m2) within the last 24 months. or 5.5. Preserved LV systolic function (LVEF =50%) with left ventricular hypertrophy (2-dimensional 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 5.6. Preserved LV systolic function (LVEF =50%) with diastolic dysfunction (septal e’ 29 ml/m2) within the last 24 months. or 5.4. 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 5.5. 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. 6. New York Heart Association Class II-IV at screening. 7. 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. 8. Kansas City Cardiomyopathy clinical summary score <85 at screening.
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 12/03/2024: 1. 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. 2. End-stage heart failure requiring left ventricular assist devices, intra-aortic balloon pump, or any type of mechanical support at the time of randomisation. 3. Documented primary severe valvular heart disease, amyloidosis or hypertrophic cardiomyopathy as principal cause of heart failure as judged by the local investigator. 4. Respiratory disease thought to be the primary cause of dyspnoea as assessed by the local investigator. 5. Chronic kidney disease with estimated glomerular filtration rate <25ml/min/1.73m² at screening. 6. Moderate or severe hepatic impairment (e.g. Child-Pugh B and C) at screening as judged by the local investigator. 7. Use of sotagliflozin or any SGLT2 inhibitor within 1 month of screening or between screening and randomisation. 8. Previous hypersensitivity/intolerance to SGLT2 inhibitors. 9. Presence of malignancy with expected life expectancy <1 year at screening. 10. Severe hypoglycaemia (hospitalisation for hypoglycaemia or episode requiring external assistance to treat) within 1 month prior to screening or between screening and randomisation. 11. 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. 12. Pregnant or lactating women. 13. Women of childbearing age or male partners of women of childbearing age and not practicing an acceptable method of birth control, see section 8.11 14. On a ketogenic diet. 15. Unwilling/unable to share glucose and ketone monitoring data. 16. Unwilling to wear continuous glucose monitoring during the trial. 17. 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. _____ Previous exclusion criteria: 1. 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. 2. End-stage heart failure requiring left ventricular assist devices, intra-aortic balloon pump, or any type of mechanical support at the time of randomisation. 3. Documented primary severe valvular heart disease, amyloidosis or hypertrophic cardiomyopathy as principal cause of heart failure as judged by the local investigator. 4. Respiratory disease thought to be the primary cause of dyspnoea as assessed by the local investigator. 5. Chronic kidney disease with estimated glomerular filtration rate <25ml/min/1.73m² at screening. 6. Severe hepatic impairment at screening as judged by the local investigator. 7. Use of sotagliflozin or any SGLT2 inhibitor within 1 month of screening or between screening and randomisation. 8. Previous hypersensitivity/intolerance to SGLT2 inhibitors. 9. Presence of malignancy with expected life expectancy <1 year at screening. 10. Severe hypoglycaemia
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Quality of life measured using the change from baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score (Weeks 0 and 16) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Quality of life measured using the change from baseline in the KCCQ clinical summary score (Weeks 0 and 4) 2. Quality of life measured using the change from baseline in the KCCQ overall summary score (Weeks 0, 4 and 16) 3. Quality of life measured using the proportion of participants with a =5, =10 and =15 point increase in KCCQ clinical and overall summary scores (Weeks 0 and 16) 4. Quality of life measured using the change from baseline in the Diabetes Treatment Satisfaction Questionnaire (Weeks 0 and 16) 5. Quality of life measured using the change from baseline in EQ-5D-5L questionnaire score (Weeks 0 and 16) 6. Walking distance measured using the change from baseline in distance covered during 6-minute walk test (Weeks 0 and 16) 7. NT-proBNP measured using the change from baseline in NT-proBNP (Week 0 and 16) 8. Glycaemic control measured using the change from baseline in HbA1c (Week 0 and 16) 9. Safety and tolerability compared to placebo measured using the proportion of participants with level 2 or level 3 hypoglycaemia (Week 0 to 16 and 20) 10. Safety and tolerability compared to placebo measured using the proportion of participants with diabetic ketoacidosis (Week 0 to 16 and 20) 11. Safety and tolerability compared to placebo measured using the proportion of participants requiring hospitalisation due to heart failure (Week 0 to 16 and 20) | — |
Countries
England, Scotland, United Kingdom
Contacts
Public ContactSusan Long
Outcome results
None listed