Dapagliflozin During Exercise for the PrevenTion of Hypoglycaemia

• Status: Suspended
• Trial end date: 2021-12-22
• Target enrollment: 0
• Participant gender: All

Summary

There are approximately 400,000 people in the UK who are living with type 1 diabetes (T1DM), of whom 29,000 are children.

People with T1DM experience on average 2 episodes of symptomatic hypoglycaemia per week , and exercise (especially aerobic) increases this risk . Strategies to prevent hypoglycaemia during and after exercise include increasing glucose consumption and reducing insulin dose, however overcompensation may result in worsening of blood glucose control.

Dysregulated glucagon secretion, manifested as a reduced counter-regulatory response during hypoglycaemia, is a key feature in T1DM, occurring soon after diagnosis.

Anecdotal evidence suggests that SGLT-2 (sodium/glucose cotransporter-2) inhibitors (SGLT2i) such as dapagliflozin prevent exercise-induced hypoglycaemia in T1DM. SGLT2is promote glucose excretion without causing hypoglycaemia.Paradoxically, given their mode of action, they increase plasma glucose and stimulate glucagon secretion. Studies in diabetic rats indicate that the physiological counter-regulatory response is suppressed in insulin-treated diabetes, a defect that can be corrected by somatostatin antagonists.

The DEPTH trial will test the novel hypothesis that hypoglycaemia results from hypersecretion of somatostatin, and that this defect can be corrected by SGLT2i. As these medications are already in clinical use, our findings may be rapidly translated into practice. Understanding these key processes has the potential to generate novel therapeutic strategies to improve glycaemic control, thereby facilitating a more active lifestyle in people with T1DM.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Oxford
• Collaborators: Oxford Brookes University; The Leona M. and Harry B. Helmsley Charitable Trust
• Treatments: Dapagliflozin

Criteria

Inclusion criteria:

1. Age 18-74

2. T1DM diagnosed at least 12 months prior to screening test

3. On insulin pump or multiple daily injections

4. HbA1c <10% (86 mmol/L)

5. Engage in some form of regular exercise

6. Have experienced at least one episode of exercise-induced hypoglycaemia

7. Adequate treatment of celiac disease if it exists.

8. Willing and able to give informed consent for participation in the trial

9. In the Investigator's opinion is able and willing to comply with all trial requirements

10. Will allow their General Practitioner to be notified of participation in the trial.

Exclusion criteria:

1. History of seizures or coma associated with hypoglycaemia in the past 2 years.

2. Active diabetic retinopathy ( including proliferative diabetic retinopathy or vitreous haemorrhage in the past 6 months).

3. Pregnant, breastfeeding, planning to become pregnant or not using adequate contraception methods (females only) during the course of the study

4. History of ischemic heart disease ( unless has had successful reperfusion), stroke/TIA, ventricular rhythm disturbances or thromboembolic disease.

5. A history of hypotension if currently on antihypertensive therapy

6. An episode of diabetic ketoacidosis in the previous 1 month

7. Currently on loop diuretics

8. On beta-blocker medication

9. A history of heart failure (NYHA Class 3 or 4)

10. A history of rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption

11. Renal impairment ( eGFR<60 ml/min/1.73m2)

12. Untreated Graves disease

13. ECG or stress test findings indicating active ischemia or a condition that would compromise the participant's safety

14. Major psychiatric disease including diagnosed eating disorders, history of drug or alcohol abuse.

15. Known or suspected allergy to trial medication

16. Oral or injectable steroid treatment 30 days prior to the start or at any time during the trial period

17. Known malignancy or any other condition or circumstances which, in the opinion of the investigator, would affect the patient's ability to participate in the protocol.

18. Receipt of any investigational trial drug within 3 months prior to participation in the current trial.