Sotagliflozin in patients with heart failure symptoms and type 1 diabetes

Phase 2

• Conditions: Type 1 Diabetes, Heart Failure; Nutritional, Metabolic, Endocrine

• Registration Number: ISRCTN79322795
• Lead Sponsor: niversity of Dundee

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-03-12
• Last Update Posted: 9 September 2024
• Study Completion: 2026-06-01

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 320

Inclusion Criteria

1. Age 18 years to <85 years.
2. Type 1 diabetes.
3. Insulin dose =0.5 units/kg body weight at screening or BMI =25kg/m2 at screening
4. Using continuous glucose monitor at screening or willing to use one for the duration of the trial.
5. Diagnosis of heart failure (HF) regardless of left ventricular ejection fraction (LVEF), defined as one or more of the following:
5.1. Previous HF hospitalisation where HF was documented as the primary cause of hospitalisation and there was a requirement for loop diuretics
or
5.2. Impaired left ventricular (LV) function (i.e. LVEF <50% by any imaging modality) at any time
or
5.3. 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
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

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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Quality of life measured using the change from baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score (Weeks 0 and 16)