Type 1 diabetes Nutritional, Metabolic, Endocrine
Conditions
Interventions
Randomised (online tool) open-label trial.
Intervention arm:
Insulin as standard of care plus semaglutide by subcutaneous injection once weekly, starting dose 0.25 mg increasing to 1.0 mg.
Control a
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Age
10 Years to 24 Years
Inclusion criteria
Inclusion criteria: 1. Children and young people aged between 10 and 24 years inclusive at screening 2. Clinical diagnosis of T1D mellitus according to World Health Organisation (WHO) or American Diabetes Association (ADA) criteria for at least 12 months prior to screening 3. On supplementary insulin of more than 0.5 unit/kg/day, using either multiple daily injections (MDI) or Continuous Subcutaneous Insulin Infusion (CSII) 4. Stable insulin requirements for the previous 3 months prior to screening (plus or minus 20% TTD between the screening visit and last NHS clinic visit) 5. Already on Continuous Glucose Monitoring Sensor (CGMS) for at least the previous 4 weeks prior to screening 6. HbA1c between 58mmol/mol and 86mmol/mol (IFCC) at screening, inclusive. This is aligned to 7.5% and 10.0% (DCCT) 7. Willingness to submit CGMS data for monitoring hypoglycaemic events 8. Able and willing to comply with all relevant protocol procedures 9. If female of childbearing potential, or male of reproductive potential, is willing to abstain from heterosexual intercourse or use a highly effective contraception method for the duration of the study 10. Able to provide informed consent (if under the age of 16 years old, informed consent will be given by parent/guardian)
Exclusion criteria
Exclusion criteria: 1. T2D or known monogenic diabetes 2. BMI less than 25th centile for age and gender (based on WHO 2007 BMI charts) if under 18 years old, and BMI less than 20 kg/m2 if 18 years or older 3. Use of any anti-diabetic agent other than insulin within 90 days prior to screening 4. Using Do-It-Yourself Closed Loop systems/Open Artificial Pancreas System 5. History of more than two severe (level 3) hypoglycaemia episodes in the last 12 months (severe hypoglycaemia is defined as a hypoglycaemic event with severe cognitive impairment (including coma and convulsions) and/or altered physical functioning that requires assistance by another person to administer carbohydrates, glucagon, or intravenous dextrose for recovery) 6. History of hypoglycaemia unawareness or a Gold score (assessment of impaired awareness of hypoglycaemia) of more than 4, as judged by the local investigator 7. History of chronic pancreatitis or idiopathic acute pancreatitis 8. Suspicion of pancreatitis as determined amylase above 150 U/L at screening 9. Any episode of diabetic ketoacidosis requiring hospital admission in the last 6 months 10. Renal function impairment defined as estimated glomerular filtration rate less than 45 ml/min/1.73m2 or creatinine above 200 µmol/L at screening: 10.1. In participants under 18 years old: eGFR will be calculated using the Schwartz equation 10.2. In participants over 18 years old: eGFR will be calculated using the CKD-EPI Equation for Estimating GFR on the Natural Scale (see Appendix 2) (of protocol) 11. Serum creatinine within age and sex specific reference ranges (see Appendix 2 of protocol) 12. Proliferative Retinopathy (R3, NHS diabetic retinopathy screening programme) 13. Calcitonin value more than 18.7 ng/L at screening 14. Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia type 2 (MEN2) 15. Diagnosis of severe gastroparesis 16. If female of childbearing potential, is pregnant at the time of screening (confirmed by a positive pregnancy test) 17. If female of childbearing potential, is actively trying to get pregnant 18. Is currently breastfeeding 19. Has a known allergy relating to semaglutide that precludes their participation in the study, in the opinion of the local investigator 20. Has a medical, social, or psychological issue that precludes their participation in the study, in the opinion of the local investigator 21. Participation in another Clinical Trial of an Investigational Medicinal Product (CTIMP)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| HbA1c measured using capillary electrophoresis at 26 weeks post-randomisation | — |
Secondary
| Measure | Time frame |
|---|---|
| Clinical: (Outcomes ranked by importance; first outcome ranked highest) 1. HbA1c measured using capillary electrophoresis at 5 and 12 weeks post-randomisation 2. Achieving target HbA1c of 48 mmol/mol or less, measured using capillary electrophoresis at 26 weeks post-randomisation 3. Glucose time in range (TIR) as a percentage, measured by continuous glucose monitoring sensor (CGMS) at 5, 12 and 26 weeks post-randomisation 4. BMI-Standard Deviation Score measured using the formula weight in kg divided by height in metres squared at 26 weeks post-randomisation 5. Total daily dose (TDD) of insulin (mean over last 3 calendar days) calculated from patient- or device-reported dose at 26 weeks post-randomisation Safety: 1. The proportion of participants who experienced at least one of the following targeted AEs (anaphylaxis, nausea, vomiting, heartburn [reflux], diarrhoea, abdominal pain, heart palpitation/racing heart, skin itching, hives, dizziness, blurred vision, lack of concentration, fatigue, diabetic ketoacidosis, hypoglycaemia) which will be considered individually, and also as the total number of these targeted AEs over the 26-week post-randomisation period, measured using AE collection form at 3, 4 7, 9, 12, 18 and 26 weeks post-randomisation 2. The proportion of participants who experienced at least one of the following targeted SAEs (anaphylaxis, nausea, vomiting, heartburn [reflux], diarrhoea, abdominal pain, heart palpitation/racing heart, skin itching, hives, dizziness, blurred vision, lack of concentration, fatigue, diabetic ketoacidosis, hypoglycaemia) which will be considered individually, and also as the total number of these targeted serious adverse events over the 26-week post-randomisation period. measured using an SAE collection form at 3, 4, 7, 9, 12, 18 and 26 weeks post-randomisation 3. Height-Standard Deviation Score in participants who are under 16 years old and have not completed puberty at 26 weeks post-randomisation Exploratory outcomes: | — |
Countries
England, United Kingdom
Outcome results
None listed