Efficacy of Closed-loop Insulin Therapy in Adults Prone to Hypoglycemia
- Conditions
- Type 1 Diabetes Mellitus With Hypoglycemia
- Interventions
- Device: Closed-loop insulin infusion driven by continuous glucose monitoring through an algorithm, in free-life conditionsDevice: Continuous Subcutaneous Insulin Infusion and Continuous Glucose Monitoring
- Registration Number
- NCT04266379
- Lead Sponsor
- University Hospital, Montpellier
- Brief Summary
This study is a RCT of 3 month at home comparing closed-loop control (CLC) system vs sensor and pump therapy (S\&P), with a 3-month extension phase, in Type 1 diabetic patient prone to hypoglycemia. After a 2-week run-in phase with blinded CGM, patients who spent 5% or more time below 70mg/dL will be eligible to continue. They will will be randomly assigned 2:1 to the use of closed-loop control (CLC) using Tandem Control-IQ vs S\&P for 3 months, which is the timing of the primary outcome for the RCT. After 3 months, the S\&P group will use CLC for up to 3 months and the CLC group will continue using CLC for up to 3 additional months.
- Detailed Description
This study is randomized controlled trial of 3 month at home closed-loop control (CLC) system vs sensor and pump therapy (S\&P), with a 3-month extension phase. The objective is to assess the efficacy and safety of home use of a Control-to-Range (CTR) closed-loop (CL) system in patients with type 1 diabetes prone to hypoglycemia.
The CLC system will consist of Tandem Control-IQ Automated Insulin Delivery System (AIDS), including Tandem X2 insulin pump with embedded Control-IQ algorithm and Dexcom G6 CGM
After consent is signed, eligibility will be assessed. All participants will initiate a run-in phase of 2 weeks of blinded Dexcom G6 CGM wear and personal insulin pump.
Prior to overall initiation of the RCT, the time spent with CGM below 70 mg/dl during the run-in phase will be assessed. Only patients showing % time with CGM \<70 mg/dl of 5% or above can be randomized. Included patients who cannot be randomized will be replaced.
Subsequent participants who show randomization criteria during the run-in phase will be randomly assigned 2:1 to the use of closed-loop control (CLC) using Tandem Control-IQ vs S\&P for 3 months, which is the timing of the primary outcome for the RCT.
After 3 months, the S\&P group will use CLC for up to 3 months and the CLC group will continue using CLC for up to 3 additional months.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 72
- Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least one year and using insulin for at least 1 year
- Use of an insulin pump for at least 6 months
- Age ≥18 .0 years old
- HbA1c level <10.5% at screening
- Clarke score >3 and/or experience of severe hypoglycemia during the previous 6 months
- For females, not currently known to be pregnant If female and sexually active, must agree to use a form of contraception to prevent pregnancy while a participant in the study. A negative serum or urine pregnancy test will be required for all premenopausal women who are not surgically sterile. Participants who become pregnant will be discontinued from the study. Also, participants who during the study develop and express the intention to become pregnant within the timespan of the study will be discontinued.
- Willingness not to use glucose-lowering agents (such as Pramlintide, Metformin, GLP-1 analogs, SGLT2 inhibitors) during the study. This does not concern treatment with Metformin active and stable for more than 3 months prior the inclusion. Moreover, the use of SGLT2 inhibitors is not allowed in the 3 months prior to enrollment.
- Willingness to suspend use of any personal CGM for the duration of the clinical trial
- Willingness to establish network connectivity on at least a weekly basis
- Currently using no insulins other than one of the following rapid-acting insulins at the time of enrollment: insulin lispro (Humalog), insulin aspart (Novolog). Patients using glulisine (Apidra) may switch to lispro or aspart at least one month prior to enrollment.
- Investigator has confidence that the participant can successfully operate all study devices and is capable of adhering to the protocol
- Subject is covered by social health or similar insurance
- Informed consent form signed
- Use of SGLT2 inhibitors in the 3 months prior to enrollment
- Hemophilia or any other bleeding disorder
- A condition, which in the opinion of the investigator or designee, would put the participant or study at risk
- Participation in another pharmaceutical or device trial at the time of enrollment or during the study
- Employed by, or having immediate family members employed by Tandem or Dexcom
- Persons deprived of freedom, protected by law or vulnerable persons
- Any associated chronic disease or therapy (except insulin) affecting glucose metabolism
- Impaired renal function (Creatinine Clearance < 30 ml/min)
- Patient who had pancreas transplantation or pancreatic islet transplantation
- Patient having severe problems of uncorrected hearing and/or visual acuity
- Subjects with known allergy to CGM adhesives
- Patients that have frequent exposure to magnetic resonance imaging (MRI), computed tomography (CT) scan, or high-frequency electrical heat (diathermy) treatment
- Patient without any social or familial support able to intervene in case of severe hypoglycemic episode
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Closed-Loop Control (CLC) Closed-loop insulin infusion driven by continuous glucose monitoring through an algorithm, in free-life conditions Closed-loop subcutaneous insulin infusion driven by continuous glucose monitoring through an algorithm Sensor Augmented Pump (SAP) Continuous Subcutaneous Insulin Infusion and Continuous Glucose Monitoring Closed-loop subcutaneous insulin infusion and continuous glucose monitoring manage by patient
- Primary Outcome Measures
Name Time Method Difference in percent of time spent with blood glucose level below 70 mg/dL 3 months Baseline-treatment difference in % of time spent with blood glucose level below 70 mg/dL over the 3 months follow-up
- Secondary Outcome Measures
Name Time Method Percent of time within target range 70-180 mg/dL 3 months Percent of time spent with blood glucose level above 180 mg/dL 3 months Mean blood glucose level 3 months Percent of time spent with blood glucose level below 54 mg/dL 3 months Percent of time spent with blood glucose in range 70-140 mg/dL 3 months Glucose variability measured with the coefficient of variation (CV) 3 months Glucose variability measured with the standard deviation (SD) 3 months Percent of time spent with blood glucose level below 60 mg/dL 3 months Low blood glucose index (LBGI) 3 months \<2.5 low risk , \[2.5-5\] medium risk, \>5 high risk
Hypoglycemia events (defined as at least 15 consecutive minutes <70 mg/dL) 3 months Percent of time spent with blood glucose level above 250 mg/dL 3 months Percent of time spent with blood glucose level above 300 mg/dL 3 months High blood glucose index (HBGI) 3 months \<2.5 low risk , \[2.5-5\] medium risk, \>5 high risk
HbA1c at 3 months at 3 months HbA1c change from baseline to 3 months 3 months Fear of Hypoglycemia Survey 3 months Total score from 0 (no fear) to 132 (important fear)
Insulin 3 months Total daily insulin (units/kg), Basal: bolus insulin ratio
Weight and Body Mass Index (BMI) 3 months Hyperglycemia Avoidance Scale 3 months Total score from 0 (do not avoid) to 40 (always avoid)
Diabetes Distress Scale 3 months Total score range from 28 (low stress) to 168 (high stress)
Hypoglycemia Confidence Scale 3 months Total score from 0 (no confidence) to 36 (very confident)
Clarke Hypoglycemia Awareness 3 months Score range from 0 to 7. If more than 4 : reduced perception, if less : normal perception.
INSPIRE survey 3 months Total score from 0 (high acceptance) to 110 (low acceptance)
System Usability Scale (SUS) 3 months Total score from 0 (low acceptance) to 100 (high acceptance)
Trial Locations
- Locations (2)
UH Montpellier
🇫🇷Montpellier, France
University Hospital of Caen
🇫🇷Caen, France