Dapagliflozin during exercise for the prevention of Hypoglycaemia in Type 1 diabetes

Phase 1

• Conditions: Type 1 diabetes mellitus; MedDRA version: 20.0 Level: PT Classification code 10067584 Term: Type 1 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders; Therapeutic area: Diseases [C] - Hormonal diseases [C19]

• Registration Number: EUCTR2017-003911-21-GB
• Lead Sponsor: niversity of Oxford

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-04-06
• Last Update Posted: 28 February 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 34

Inclusion Criteria

1. Age >18
2. Type 1 diabetes diagnosed at least 12months prior to screening test
3. On insulin pump or multiple daily injections
4. HbA1c <10% (86mmol/mol)
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. Willing to allow their General Practitioner and/or consultant, if appropriate, to be notified of participation in the trial.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 34
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

1. History of seizure 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 or planning to become pregnant 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. Renal impairment (eGFR <60ml/min/1.73m2)
6. Untreated Graves disease
7. ECG or stress test findings indicating active ischemia or a condition that would compromise the participant’s safety
8. Major psychiatric disease including diagnosed eating disorders, history of drug or alcohol abuse
9. Known or suspected allergy to trial medication
10. Oral or injectable steroid treatment 30 days prior to the start or at any time during the trial period
11. On beta-blocker medication
12. Known malignancy or any other condition or circumstance which, in the opinion of the investigator, would affect the patient’s ability to participate in the protocol
13. Receipt of any investigational trial drug within 3 month prior to participation in the current trial.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary end point(s): Time to hypoglycemia during exercise challenge (before and after dapagliflozin treatment), and between treatment groups.;Timepoint(s) of evaluation of this end point: Exercise challenge in part A and part B.;Main Objective: To determine whether dapagliflozin (either taken regularly or as a single dose) can delay/prevent the onset of hypoglycaemia during moderate intensity exercise.;<br> Secondary Objective: 1. Whether dapagliflozin can prevent late-onset exercise-induced hypoglycaemia (overnight or the following day).<br><br> 2. Measure the release of glucagon and somatostatin during and after exercise, on and off dapagliflozin.<br><br> 3. Determine the changes in plasma electrolytes during exercise.<br>

Secondary Outcome Measures

Name	Time	Method
<br> Secondary end point(s): 1.Duration of time in hypoglycaemia (categorised as <4mmol/L or <3mmol/L) from CGM recordings before and after dapagliflozin treatment, and between treatment groups.<br><br> 2.Concentration of plasma glucose, glucagon and somatostatin-14 (pancreatic-specific) at each 10min interval during exercise challenge.<br><br> 3.Concentration of plasma potassium, sodium, calcium and pH at each 10min interval during exercise challenge.<br> ;<br> Timepoint(s) of evaluation of this end point: 1.24-hour period after each exercise challenge.<br><br> 2.10 minute intervals during each exercise challenge.<br><br> 3.10 minute intervals during each exercise challenge.<br>