None listed
Conditions
Brief summary
Although sodium glucose transporter inhibitors (SGLT2i) are approved in Australia (TGA) for the treatment of children with type 2 diabetes (T2D), their use in people with type 1 diabetes (T1D) is not approved due to the increased incidence of DKA. However, trials have utilised risk-minimising strategies in children and adults to reduce DKA and gain the overall benefits of SGLT2i in diabetes management. This study utilises a Dual Glucose and Ketone (DGK) monitor with a management plan to recognise early ketosis and intervene appropriately. This is a 14-week randomised controlled study in children with T1D on SGLTi (dapaglifozin). Two ketone thresholds available in real-time from DGK monitor will be evaluated at 1.0 mmol/L and 1.5 mmol/L with education provided regarding the user intervention. The primary objective is to determine whether DGK in conjunction with user response initiated at 1.0 mmol/L is more effective than 1.5 mmol/L in reducing the time spent with ketone levels greater than or equal to 3.0mmol/L. In this randomised parallel-arm study, participants will undergo a 2-week run-in period and will then be randomly assigned 1:1 to two groups. Group 1 will receive education about Algorithm 1 (responses at ketone threshold of 1.0 mmol/L) and Group 2 will receive education about Algorithm 2 (responses at ketone threshold of 1.5 mmol/L).
Interventions
Dapagliflozin is a SGLT2 inhibitor (SGLT2i) with the potential to improve glycaemia but has an increased risk of diabetic ketoacidosis (DKA) even without hyperglycaemia. This study utilises a Dual Glucose and Ketone (DGK) monitor with a management plan to recognise early ketosis and intervene appropriately.
Participants aged 13-24 years with type 1 diabetes (T1D) will undertake a 2-week run-in period during which they will wear an investigational Abbott Diabetic Glucose-Ketone Monitor (DGK), co
Dapagliflozin is a SGLT2 inhibitor (SGLT2i) with the potential to improve glycaemia but has an increased risk of diabetic ketoacidosis (DKA) even without hyperglycaemia. This study utilises a Dual Glucose and Ketone (DGK) monitor with a management plan to recognise early ketosis and intervene appropriately. Participants aged 13-24 years with type 1 diabetes (T1D) will undertake a 2-week run-in period during which they will wear an investigational Abbott Diabetic Glucose-Ketone Monitor (DGK), comprising a continuous ketone monitor (CKM) and continuous glucose monitor (CGM), and receive standard sick-day management education. The DGK device is a wearable sensor applied to the participant's skin according to the manufacturer's instructions. Following successful completion of the run-in period, participants will commence dapagliflozin (International Non-proprietary Name [INN]) 5 mg once daily, administered as an oral tablet, for 12 weeks in addition to their usual insulin therapy. Participants will then be randomised 1:1 to one of two intervention groups: Arm 1: DGK ketone alarm threshold set at 1.0 mmol/L Arm 2: DGK ketone alarm threshold set at 1.5 mmol/L The DGK continuously measures interstitial glucose and ketone levels and transmits readings every 5 minutes to a smartphone application. Participants in both groups will receive structured education by a Diabetes educator during the run-in period. They will also be provided with and trained in the use of a study blood glucose / ketone meter (Freestyle Optium / Precision Neo Blood Glucose Meter, Abbott Diabetes Care), which will be used for confirmatory blood glucose and ketone testing as clinically indicated. In addition, sick day education will be reinforced emphasising the review of ketone levels though no education regarding ketone threshold levels and response strategies will be provided. This education is based on the STICH protocol52 (Stop, Inject, Carbohydrate and Hydrate) principles. Participants will be instructed to wear the DGK continuously throughout the study. Adherence will be supported through device training, structured education, a 24-hour study support contact, participant diaries, and scheduled remote safety reviews at 48 hours, 2 weeks, 4 weeks, and 8 weeks following randomisation. Device data will be reviewed regularly to assess continuous sensor wear, ketone and glucose levels, and compliance with study procedures. Participants using multiple daily insulin injections will also maintain insulin dose diaries, and all participants will record dietary carbohydrate intake during specified study periods. To ensure the safety of participants whilst participating in the study, safety monitoring will occur remotely by telephone call by the study doctor or study coordinator. During these follow-ups, study DGK data will be reviewed using the cloud-based platform Libreview to ensure that their glucose and ketone levels are in a safe range, and that the DGK is being worn and functioning correctly. Any adverse events will also be recorded during these sessions. Safety monitoring will occur at 48 hours (Day 2 / Visit 3), two weeks (Week 2 / Visit 4), four weeks (Week 4 / Visit 5) and eight weeks (Week 8 / Visit 6) post-randomisation. More frequent reviews may be conducted if required depending upon the participant’ needs. Exercise sub-study (optional): Participation in the exercise sub-study is optional, and not all participants will take part. Only participants who provide separate consent for the sub-study and have been taking dapagliflozin (5 mg/day) for at least 4 weeks will be eligible. These participants will complete four supervised cycling exercise sessions (two morning high-intensity and two evening long-duration sessions) between Weeks 4 and 12. Sessions will be conducted at the study site to evaluate the impact of different DGK ketone alert thresholds (1.0 mmol/L vs 1.5 mmol/L) on post-exercise ketosis and will supervised by an endocrinologist and study nurse.. Blood glucose and ketone levels will be monitored throughout the sessions to ensure participant safety. During the morning high-intensity session, participants will undergo a total of 40 mins of exercise on a stationary bike, compromised of 20 mins (5x 4 mins) of high-intensity ( approximately 80-90% max heart rate using a heart rate monitor), interspersed with 20 mins (5x 4 mins) of low intensity cycling/ active rest, During the evening long-duration session, participants will complete a total of 60 mins continuous cycling on a stationary exercise bike at approximately 60% max heart rate. Immediately after, participants will then complete six high-intensity cycling sprints of 30 sec intervals, interspaced with 4 mins recovery (low intensity cycling or rest). Each session must be scheduled at least 24 hours apart to allow insulin-sensitising effects of antecedent exercise to wash out.
Sponsors
The Kids Research Institute Australia
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
13 Years to 24 Years
Healthy volunteers
No
Inclusion criteria
• Aged between 13 and 24 years of age inclusive • Diagnosed with T1D for at least 1 year • Insulin regimen either on MDI or insulin pump • Minimum total daily insulin dose 0.4 Units per kg/day (can be on insulin pump or Multiple Daily Injections (MDI)) • HbA1c <9% (86mmol/ mol) • Minimum daily carbohydrate intake of 100g • Willing to adhere to the study protocol • Ability to perform high-intensity exercise (specific to the exercise sub-study)
Exclusion criteria
• Pregnancy or planned pregnancy • eGFR <30ml/min/1.73m2 • History of DKA in the last 12 months • Use of low carbohydrate diet (<100g/day) • Diabetic gastroparesis • Tape allergy • Heavy alcohol use (15 standard drinks per week or binge drinking) • Use of SGLT inhibitor in the last month • Medications increasing the risk of DKA e.g. steroids, anorectic agents (eg phentermine, naltrexone HCl/bupropion HCl, and GLP 1 RA agonists). • Major medical or psychiatric illness that in the opinion of the investigator would interfere with protocol adherence or impact participant safety. If participants who were deemed eligible to participate at screening and were recruited into the study, lose the capacity to provide ongoing consent they will be withdrawn from the study.
Outcome results
None listed