Clinical trial NCT04266379: Efficacy of Closed-loop Insulin Therapy in Adults Prone to Hypoglycemia
Official title: A Randomized Clinical Trial to Assess the Efficacy of Adjunctive Closed Loop Control Versus Sensor and Pump Therapy in the Management of Type 1 Diabetes Prone to Hypoglycemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Type 1 Diabetes Mellitus With Hypoglycemia
Keywords: Type 1 diabetes
Hypoglycemia
Closed-loop insulin infusion
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
Collaborators: name: Tandem Diabetes Care, Inc.
name: DexCom, Inc.
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: University of Virginia
First posted: 2020-02-12
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least one year and using insulin for at least 1 year
2. Use of an insulin pump for at least 6 months
3. Age ≥18 .0 years old
4. HbA1c level \<10.5% at screening
5. Clarke score \>3 and/or experience of severe hypoglycemia during the previous 6 months
6. 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.
7. 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.
8. Willingness to suspend use of any personal CGM for the duration of the clinical trial
9. Willingness to establish network connectivity on at least a weekly basis
10. 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.
11. Investigator has confidence that the participant can successfully operate all study devices and is capable of adhering to the protocol
12. Subject is covered by social health or similar insurance
13. Informed consent form signed

Exclusion Criteria:

1. Use of SGLT2 inhibitors in the 3 months prior to enrollment
2. Hemophilia or any other bleeding disorder
3. A condition, which in the opinion of the investigator or designee, would put the participant or study at risk
4. Participation in another pharmaceutical or device trial at the time of enrollment or during the study
5. Employed by, or having immediate family members employed by Tandem or Dexcom
6. Persons deprived of freedom, protected by law or vulnerable persons
7. Any associated chronic disease or therapy (except insulin) affecting glucose metabolism
8. Impaired renal function (Creatinine Clearance \< 30 ml/min)
9. Patient who had pancreas transplantation or pancreatic islet transplantation
10. Patient having severe problems of uncorrected hearing and/or visual acuity
11. Subjects with known allergy to CGM adhesives
12. Patients that have frequent exposure to magnetic resonance imaging (MRI), computed tomography (CT) scan, or high-frequency electrical heat (diathermy) treatment
13. Patient without any social or familial support able to intervene in case of severe hypoglycemic episode

Primary outcomes:
measure: Difference in percent of time spent with blood glucose level below 70 mg/dL
timeFrame: 3 months
Secondary outcomes:
measure: Percent of time within target range 70-180 mg/dL
timeFrame: 3 months
measure: Percent of time spent with blood glucose level above 180 mg/dL
timeFrame: 3 months
measure: Mean blood glucose level
timeFrame: 3 months
measure: Percent of time spent with blood glucose level below 54 mg/dL
timeFrame: 3 months
measure: Percent of time spent with blood glucose in range 70-140 mg/dL
timeFrame: 3 months
measure: Glucose variability measured with the coefficient of variation (CV)
timeFrame: 3 months
measure: Glucose variability measured with the standard deviation (SD)
timeFrame: 3 months
measure: Percent of time spent with blood glucose level below 60 mg/dL
timeFrame: 3 months
measure: Low blood glucose index (LBGI)
timeFrame: 3 months
measure: Hypoglycemia events (defined as at least 15 consecutive minutes <70 mg/dL)
timeFrame: 3 months
measure: Percent of time spent with blood glucose level above 250 mg/dL
timeFrame: 3 months
measure: Percent of time spent with blood glucose level above 300 mg/dL
timeFrame: 3 months
measure: High blood glucose index (HBGI)
timeFrame: 3 months
measure: HbA1c at 3 months
timeFrame: at 3 months
measure: HbA1c change from baseline to 3 months
timeFrame: 3 months
measure: Fear of Hypoglycemia Survey
timeFrame: 3 months
measure: Hyperglycemia Avoidance Scale
timeFrame: 3 months
measure: Diabetes Distress Scale
timeFrame: 3 months
measure: Hypoglycemia Confidence Scale
timeFrame: 3 months
measure: Clarke Hypoglycemia Awareness
timeFrame: 3 months
measure: INSPIRE survey
timeFrame: 3 months
measure: System Usability Scale (SUS)
timeFrame: 3 months
measure: Insulin
timeFrame: 3 months
measure: Weight and Body Mass Index (BMI)
timeFrame: 3 months
Other outcomes:
Locations:
city: Caen
country: France
facility: University Hospital of Caen
city: Montpellier
country: France
facility: UH Montpellier
Study officials:
affiliation: Montpellier University Hospital
name: Eric M RENARD, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: