Type 1 diabetes mellitus Nutritional, Metabolic, Endocrine Type 1 diabetes mellitus
Conditions
Interventions
The LEGEND-D trial is a pilot, randomised cross-over, single-centre, non-blinded, clinical trial which aims to investigate the effect low doses of glibenclamide (0.3 mg, 0.6 mg and 3 mg/day) and dapag
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Type 1 diabetes group: 1. Type 1 diabetes diagnosed =12 months prior to screening 2. Age 18-75 years 3. Either on insulin pump or multiple daily injections 4. HbA1c <10% (86 mmol/mol) at screening 5. Prior training regarding insulin dose-adjustment and management of hypoglycaemia 6. Willing and able to give informed consent for participation in the trial 7. In the Investigator’s opinion is able and willing to comply with all trial requirements Non-diabetic group: 1. Age 18-75 years 2. HbA1c =6.0% (42 mmol/mol) at screening 3. Willing and able to give informed consent for participation in the trial 4. In the Investigator’s opinion is able and willing to comply with all trial requirements
Exclusion criteria
Exclusion criteria: Type 1 diabetes group only: 1. An episode of diabetic ketoacidosis in the previous 1 month 2. Severe hypoglycaemia requiring third party intervention on more than one occasion in the preceding 12 months 3. Active diabetic retinopathy (including proliferative diabetic retinopathy or vitreous haemorrhage in the past 6 months) Type 1 diabetes and non-diabetic group: 1. Haemoglobin 2.5×upper limit of the assay normal range or known liver disease, specifically bilirubin >30 µmol/L that is associated with other evidence of liver failure. 6. Uncontrolled hypertension (>180 mmHg systolic or > 100 mmHg diastolic) 7. History of ischaemic heart disease (unless has had successful reperfusion), stroke/transient ischaemic attack, ventricular rhythm disturbances or thromboembolic disease 8. On beta-blocker medication 9. A history of heart failure (New York Heart Association Class 3 or 4) 10. Untreated Grave’s disease 11. History of ECG or stress test findings indicating active ischaemia or a condition that would compromise the participant’s safety 12. Known history of porphyria 13. Concomitant use of bosentan 14. Known or suspected allergy to the trial product or related products 15. Have received any investigational drug within 3 months prior to screening 16. Systemic (i.e. other than topical) corticosteroid treatment within 30 days prior to the start or at any time during the trial period 17. Major psychiatric disease including eating disorders, history of drug and alcohol abuse 18. Known malignancy or any other condition or circumstance which, in the opinion of the investigator, would affect the participant’s ability to participate in the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Concentration of plasma glucagon will be measured at 40 min during the hypoglycaemic phase of the hyper-insulinaemic hypo-glycaemic clamp, at baseline (no medication) and at each dose step of glibenclamide. This will be performed only in participants with type 1 diabetes | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Concentration of plasma glucagon measured during the hypoglycaemic phase of the hyperinsulinaemic hypoglycaemic clamp at 0, 15, 30 and 40 minutes. This will be carried out at baseline (no medication) for participants with and without type 1 diabetes, and at each dose step of glibenclamide for participants with type 1 diabetes. 2. Proportion of increase in plasma glucagon quantified by calculating the ratio between glucagon concentrations during the hypoglycaemic and euglycaemic phase at 0, 15, 30 and 40 min (e.g. glucagon concentration at 0 min during the hypoglycaemic phase divided by the glucagon concentration at 0 min during the euglycaemic phase). This will be carried out for participants with and without type 1 diabetes. 3. Percentage of time spent in hypoglycaemia (<4.0 mmol/L) measured from all Freestyle libre data collected at each dose step until the start of the hyper-insulinaemic hypo-glycaemic clamp from Freestyle Libre 2 data. This will be performed only on participants with type 1 diabetes. 4. Proportion of change in plasma glucagon measured by calculating the ratio between glucagon concentrations during the hypoglycaemic and euglycaemic phase at 0, 15, 30 and 40 min. This will be carried out at baseline (no medication) for participants with and without type 1 diabetes, and after a single dose of dapagliflozin 10 mg in participants with type 1 diabetes. 5. Proportion of change in plasma somatostatin measured by calculating the ratio between somatostatin concentrations during the hypoglycaemic and euglycaemic phase at 0, 15, 30 and 40 min. This will be carried out at baseline (no medication) for participants with and without type 1 diabetes, and after a single dose of dapagliflozin 10 mg in participants with type 1 diabetes. 6. Fasting C-peptide measured prior to the baseline hyperinsulinaemic hypoglycaemic clamp by quantifying plasma C-peptide level at the start of the hyperinsulinaemic hypoglycaemic clamp (participants with type 1 diabetes only). | — |
Countries
England, United Kingdom
Contacts
Public ContactNkemjika Abiakam
Outcome results
None listed