Sotagliflozin in Patients With Heart Failure Symptoms and Type 1 Diabetes

NCT06435156 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 01-50-233-SRA-2023-1376-M-B1007807
• Study Type: interventional
• Target: 320
• Locations: 1 country
• Sites: 15

Brief Summary

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.

Conditions

Type 1 Diabetes; Heart Failure

Keywords

Type 1 Diabetes; heart failure; Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors; sotagliflozin

Outcome Measures

Primary Outcomes (1)

• Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score

  To investigate the effect of sotagliflozin 200mg once daily in addition to standard of care on quality of life (QoL). KCCQ clinical summary score (no unit, ranges from 0 to 100 with higher scores reflecting better health status).

  From baseline to week 16

Secondary Outcomes (11)

• Change in KCCQ clinical summary score

  From baseline to week 4

• Change in KCCQ overall summary score

  From baseline to weeks 4 and 16

• Proportion of participants with a ≥5, ≥10 and ≥15 point increase in KCCQ clinical and overall summary scores

  From baseline to week 16

• Change in Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) and Change (DTSQc)

  From baseline to week 16

• Change in EQ-5D-5L questionnaire score

  From baseline to week 16

Other Outcomes (16)

• Change in New York Heart Association (NYHA) class

  From baseline to weeks 16 and 20

• Change in daily loop diuretic dose

  From baseline to week 16

• Change in systolic and diastolic blood pressure.

  From baseline to week 16

Study Arms (2)

Sotagliflozin

EXPERIMENTAL

Sotagliflozin oral tablet, 200mg once per day for 16 weeks.

Drug: Sotagliflozin

Placebo

PLACEBO COMPARATOR

Placebo oral tablet, 200mg once per day for 16 weeks.

Drug: Placebo

Interventions

Sotagliflozin DRUG

Sodium-glucose Co-transporter inhibitor

Sotagliflozin

Placebo DRUG

Matched placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 84 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Impaired left ventricular (LV) function (i.e. LVEF \<50% by any imaging modality) at any time
• 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.
• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Dundee: lead
• Lexicon Pharmaceuticals: collaborator
• Juvenile Diabetes Research Foundation: collaborator

Study Sites (15)

Aberdeen Royal Infirmary

Aberdeen, AB25 2ZN, United Kingdom

RECRUITING

Addenbrookes Hospital

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

Ninewells Hospital

Dundee, DD1 9SY, United Kingdom

RECRUITING

Royal Infirmary of Edinburgh

Edinburgh, EH16 4SA, United Kingdom

RECRUITING

Glasgow Royal Infirmary, Glasgow Clinical Research Facility

Glasgow, G31 2ER, United Kingdom

RECRUITING

Leicester General Hospital

Leicester, LE5 4PW, United Kingdom

RECRUITING

Aintree University Hospital

Liverpool, L9 7AL, United Kingdom

RECRUITING

Prince Philip Hospital

Llanelli, SA14 8QF, United Kingdom

RECRUITING

Guy's Hospital

London, SE1 9RT, United Kingdom

RECRUITING

St George's University Hospitals NHS Foundation Trust

London, SW17 0QT, United Kingdom

RECRUITING

Manchester Royal Infirmary Hospital

Manchester, M13 9WL, United Kingdom

RECRUITING

Wythenshawe Hospital

Manchester, M23 9LT, United Kingdom

RECRUITING

North Manchester General Hospital

Manchester, M8 5RB, United Kingdom

RECRUITING

Northern General Hospital

Sheffield, S5 7AU, United Kingdom

RECRUITING

Moorgreen Hospital

Southampton, SO30 3JB, United Kingdom

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Heart Failure

Interventions

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Heart Diseases; Cardiovascular Diseases

Study Officials

• Ify Mordi, MBChB, MD

  University of Dundee

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ify Mordi, MBChB, MD

CONTACT

+44 1382 385591; i.mordi@dundee.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Senior Lecturer and Honorary Consultant Cardiologist

Study Record Dates

• First Submitted: May 16, 2024
• First Posted: May 30, 2024
• Study Start: January 28, 2025
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2027
• Last Updated: August 21, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (15)