Sotagliflozin in patients with heart failure symptoms and type 1 diabetes
| ISRCTN | ISRCTN79322795 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN79322795 |
| IRAS number | 1007807 |
| ClinicalTrials.gov number | NCT06435156 |
| Secondary identifying numbers | 01-50-23, IRAS 1007807, CPMS 61046 |
- Submission date
- 23/01/2024
- Registration date
- 12/03/2024
- Last edited
- 14/04/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English Summary
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 June 2026
Who is funding the study?
Juvenile Diabetes Research Foundation United Kingdom
Who is the main contact?
Dr Joel Rocha, sophist-trial@dundee.ac.uk
Contact information
Scientific, Principal Investigator
Ninewells Hospital and Medical School
Dundee
DD1 9SY
United Kingdom
| Phone | +44 (0)1382 385591 |
|---|---|
| i.mordi@dundee.ac.uk |
Public
Tayside Clinical Trials Unit (TCTU)
Tayside Medical Science Centre (TASC)
Residency Block, Level 3 George Pirie Way
Ninewells Hospital and Medical School
Dundee
DD1 9SY
United Kingdom
| Phone | +44 (0)1382 388596 |
|---|---|
| sophist-trial@dundee.ac.uk |
Study information
| Study design | Interventional double-blind randomized parallel group placebo-controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised parallel trial |
| Study setting(s) | Hospital |
| Study type | Safety, Efficacy |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | A phase 2 double-blind randomised controlled trial studying the effect of sotagliflozin 200mg once daily versus placebo in individuals with heart failure and type 1 diabetes on quality of life measured using the Kansas City Cardiomyopathy Questionnaire |
| Study acronym | SOPHIST |
| Study hypothesis | Primary objectives: To investigate the effect of sotagliflozin 200mg once daily in addition to standard of care on quality of life Secondary objectives: 1. To investigate the effect of sotagliflozin 200mg once daily in addition to standard of care on walking distance 2. To investigate the effect of sotagliflozin 200mg once daily in addition to standard of care on NT-proBNP 3. To investigate the effect of sotagliflozin 200mg once daily in addition to standard of care on glycaemic control 4. To provide information on safety and tolerability of sotagliflozin 200mg once daily in addition to standard of care compared to placebo |
| Ethics approval(s) |
Approved 11/03/2024, Yorkshire & The Humber - Leeds West Research Ethics Committee (NHSBT Newcastle Blood Donor Centre, Holland Drive, Newcastle upon Tyne, NE2 4NQ, United Kingdom; +44 207 104 8141; leedswest.rec@hra.nhs.uk), ref: 24/YH/0028 |
| Condition | Type 1 Diabetes, Heart Failure |
| Intervention | 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 Placebo arm: Matching placebo, 200 mg oral tablets once per day for 16 weeks Participants in both arms will be assessed during the treatment period (i.e. 16 weeks) and at follow-up 4 weeks later (i.e. week 20). |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Prophylaxis, Therapy |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Sotagliflozin |
| Primary outcome measure | Quality of life measured using the change from baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score (Weeks 0 and 16) |
| Secondary outcome measures | 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) |
| Overall study start date | 18/01/2024 |
| Overall study end date | 01/06/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 85 Years |
| Sex | Both |
| Target number of participants | 320 |
| Participant 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. |
| Participant 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. |
| Recruitment start date | 28/01/2025 |
| Recruitment end date | 01/11/2025 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
Study participating centres
Dundee
DD1 9SY
United Kingdom
Leicester
LE5 4PW
United Kingdom
West End
Southampton
SO30 3JB
United Kingdom
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Wythenshawe
Manchester
M23 9LT
United Kingdom
London
SW17 0QT
United Kingdom
Old Dalkeith Road
Lothian
EH16 4SA
United Kingdom
Dafen
Llanelli
SA14 8QF
United Kingdom
Glasgow
G4 0SF
United Kingdom
Sponsor information
University/education
Ninewells Hospital and Medical School
Dundee
DD1 9SY
Scotland
United Kingdom
| Phone | +44 (0)1382 383297 |
|---|---|
| TASCgovernance@dundee.ac.uk | |
| Website | https://www.dundee.ac.uk/tasc/ |
"ROR" |
https://ror.org/03h2bxq36 |
Funders
Funder type
Charity
Government organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Juvenile Diabetes Research Foundation Ltd, JUVENILE DIABETES RESEARCH FOUNDATION LIMITED, JDRF UK, JDRF
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/06/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Peer reviewed scientific journals Internal report Conference presentation Publication on website Submission to regulatory authorities Other Consent will be sought for data to be shared for the purposes of research. Any information which identifies the participant will be removed prior to sharing. |
| IPD sharing plan | Datasets of pseudo-anonymised individual participant data generated and/or analysed during the current study will be available upon request from the Chief Investigator Dr Ify Mordi (i.mordi@dundee.ac.uk) at the end of the trial (i.e. when all endpoints/outcomes have been met, key analyses are complete and results published in peer-reviewed scientific journals). Data will remain available for at least 25 years. Data will only be released for legitimate secondary research purposes, where the Chief Investigator (Dr Ify Mordi) agrees that the proposed use has scientific value and will be carried out to a high standard (in terms of scientific rigour and information governance and security), and that there are resources available to satisfy the request. Data will only be released in line with participants' consent, all applicable laws relating to data protection and confidentiality, and any existing contractual obligations. No individual participant data will be released before an appropriate agreement is in place setting out the conditions of release. The agreement will govern data retention, usually stipulating that data recipients must delete their copy of the released data at the end of the planned project. |
Editorial Notes
14/04/2025: The study participating centre Glasgow Royal Infirmary was added.
07/04/2025: The study participating centres Royal Infirmary in Edinburgh and Prince Philip Hospital in Llanelli were added.
27/03/2025: The study participating centre St Georges Hospital was added.
21/03/2025: The study participating centre Manchester Wythenshawe Hospital was added.
19/03/2025: The study participating centre Addenbrookes was added.
19/02/2025: The study participating centre Moorgreen Hospital was added.
03/02/2025: The study participating centre Leicester General Hospital was added.
29/01/2025: The recruitment start date was changed from 03/02/2025 to 28/01/2025.
20/01/2025: The study website was added.
17/01/2025: The recruitment start date was changed from 06/01/2025 to 03/02/2025.
31/10/2024: The recruitment start date was changed from 01/11/2024 to 06/01/2025.
27/08/2024: The recruitment start date was changed from 01/09/2024 to 01/11/2024.
28/06/2024: The following changes were made:
1. The recruitment start date was changed from 30/06/2024 to 01/09/2024.
2. ClinicalTrials.gov number added.
01/05/2024: The recruitment start date was changed from 01/05/2024 to 30/06/2024.
05/04/2024: Internal review.
12/03/2024: The following changes were made to the trial record:
1. The exclusion criteria were changed.
2. The ethics approval was added.
23/01/2024: Trial's existence confirmed by NHS HRA.
