Sotagliflozin in patients with heart failure symptoms and type 1 diabetes
Trial ID: ISRCTN79322795
Other - Phase 2 - Recruiting
Background and study aims
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 potentially 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 we do not know if these benefits also apply to this population.
Who can participate?
People aged 18 to 85 years with type 1 diabetes and heart failure symptoms
What does the study involve?
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 about 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.
What are the possible benefits and risks of participating?
By taking part you are contributing to medical science. The results may help other people in the future. If we find that sotagliflozin does make people with type 1 diabetes and heart failure feel better, then we might use sotagliflozin to treat people like you in future.
You’ll be monitored closely during the trial by the trial team. If any of the investigations and assessments reveal any new clinically significant abnormality, we’ll tell you and either discuss this with your GP (with your consent) or refer you to a specialist clinic at the hospital. We’ll also be reviewing your current treatment for diabetes and heart failure and may be able to help improve this.
If sotagliflozin has the same effect as SGLT inhibitors have in people with type 2 diabetes or people without diabetes, and you are allocated to take sotagliflozin in this trial you might notice that your heart failure symptoms improve. You may also find that your glucose levels improve.
Diabetic ketoacidosis (DKA): SGLT2i therapy in type 1 diabetes is associated with an increased risk (~3%) of DKA. Participants will be asked to perform capillary ketone testing 4 times per day 3 days before and 3 days after initiation of active drug/placebo and 2 hours after changing each insulin giving set for those on insulin pump therapy as described earlier. They will also be given advice on ketone recording when unwell.
Hypoglycaemia: there is a small increased risk of severe hypoglycaemia with sotagliflozin. Once randomisation is complete, participants with a HbA1c <58mmol/l will have a 10% insulin dose reduction prior to taking their first dose of sotagliflozin/placebo to reduce the risk of severe hypoglycaemia. Further dose adjustments will be given to all participants throughout the trial if required.
All patients with type 1 diabetes will routinely be given advice about DKA and hypoglycaemia within their standard care. This prior knowledge will be supplemented with additional education around preventing, recognising and treating DKA and hypoglycaemia and will be given along with support information to take away. All participants will be using a continuous glucose monitoring system to record their blood glucose levels and will have a ketone meter to record ketone levels as advised. At each visit glucose and ketone readings will be reviewed with the participant and further advice on diabetes management given as required.
Genital/Urinary Tract Infections: Advice will be given on the risk of urogenital infection given at the randomisation visit as per standard initiation of SGLT2 inhibitors.
Volume Depletion: Advice will be given regarding “sick day rules” as per the STOP-DKA protocol
Deterioration in renal function: renal function will be assessed at visits 3, 5 and 7.
Attendance at research visits: where possible visits can be carried out via telephone or video calls.
Monitoring of glucose and ketone levels: PPI review highlighted that this may be a burden for participants. This has been kept to a minimum whilst still ensuring participant safety. All participants will be using continuous glucose monitoring (CGM) systems as standard care for people with type 1 diabetes, glucose monitoring will not therefore be more than usual for this population. We will encourage all participants to use a mobile app which records readings from the CGM this can be shared with the research team to allow for review of glucose readings for diabetes management and reduces the need for participants to document glucose readings.
Where is the study run from?
Ninewells Hospital and Medical School (UK)
When is the study starting and how long is it expected to run for?
January 2024 to October 2027
Who is funding the study?
Breakthrough T1D: Type 1 Diabetes (formerly Juvenile Diabetes Research Foundation United Kingdom).
Who is the main contact?
Ms Susan Long, sophist-trial@dundee.ac.uk
Conditions
- Type 1 Diabetes, Heart Failure
- Nutritional, Metabolic, Endocrine
Interventions
Eligibility
Inclusion criteria
- Current key inclusion criteria as of 11/05/2026:
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 a continuous glucose monitor at screening or willing to use one for the duration of the trial.
5. Diagnosis of heart failure (HF) or high-risk for HF, defined as any of the following:
5.1. NT- pro-BNP ≥250ng/L for those in atrial fibrillation/flutter, ≥125 ng/L for those in all other rhythms
or
5.2. Previous HF hospitalisation where HF was documented as the primary cause of hospitalisation and there was a requirement for loop diuretics
or
5.3. Impaired left ventricular (LV) function (i.e. LVEF <50% by any imaging modality) at any time
or
5.4. Preserved LV systolic function (LVEF ≥50%) with left atrial enlargement (2-dimensional 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
5.5. 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’ <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. Kansas City Cardiomyopathy clinical summary score <85 at screening.
Previous key 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 a 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 (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.
Sponsor
University of Dundee
Source: https://www.isrctn.com/
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