Efficacy of Closed-loop Insulin Therapy in Adults Prone to Hypoglycemia

Type 1 Diabetes Mellitus With Hypoglycemia Clinical Trial

— DCLP2  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04266379
• Other study ID #: RECHMPL19_0351-(7826)
• Secondary ID: 2019-A01906-51CI
• Status: Recruiting
• Phase: N/A
• Start date: May 13, 2020
• Est. completion date: February 3, 2023

Study information

• Verified date: December 2021
• Source: University Hospital, Montpellier
• Contact: Eric M RENARD, MD, PhD
• Phone: +33 467 338 382
• Email: e-renard[@]chu-montpellier.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: February 3, 2023
• Est. primary completion date: November 3, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Hypoglycemia
• Type 1 Diabetes Mellitus With Hypoglycemia

Intervention

Device:
• Closed-loop insulin infusion driven by continuous glucose monitoring through an algorithm, in free-life conditions
Continuous subcutaneous insulin infusion according to an automated algorithm from continuous glucose monitoring data
• Continuous Subcutaneous Insulin Infusion and Continuous Glucose Monitoring
Insulin delivered subcutaneously by a pump and manage by the patient with the help of a CGM sensor

Locations

Country	Name	City	State
France	University Hospital of Caen	Caen
France	UH Montpellier	Montpellier

Sponsors (5)

Lead Sponsor	Collaborator
University Hospital, Montpellier	DexCom, Inc., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Tandem Diabetes Care, Inc., University of Virginia

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in percent of time spent with blood glucose level below 70 mg/dL	Baseline-treatment difference in % of time spent with blood glucose level below 70 mg/dL over the 3 months follow-up	3 months
Secondary	Percent of time within target range 70-180 mg/dL		3 months
Secondary	Percent of time spent with blood glucose level above 180 mg/dL		3 months
Secondary	Mean blood glucose level		3 months
Secondary	Percent of time spent with blood glucose level below 54 mg/dL		3 months
Secondary	Percent of time spent with blood glucose in range 70-140 mg/dL		3 months
Secondary	Glucose variability measured with the coefficient of variation (CV)		3 months
Secondary	Glucose variability measured with the standard deviation (SD)		3 months
Secondary	Percent of time spent with blood glucose level below 60 mg/dL		3 months
Secondary	Low blood glucose index (LBGI)	<2.5 low risk , [2.5-5] medium risk, >5 high risk	3 months
Secondary	Hypoglycemia events (defined as at least 15 consecutive minutes <70 mg/dL)		3 months
Secondary	Percent of time spent with blood glucose level above 250 mg/dL		3 months
Secondary	Percent of time spent with blood glucose level above 300 mg/dL		3 months
Secondary	High blood glucose index (HBGI)	<2.5 low risk , [2.5-5] medium risk, >5 high risk	3 months
Secondary	HbA1c at 3 months		at 3 months
Secondary	HbA1c change from baseline to 3 months		3 months
Secondary	Fear of Hypoglycemia Survey	Total score from 0 (no fear) to 132 (important fear)	3 months
Secondary	Hyperglycemia Avoidance Scale	Total score from 0 (do not avoid) to 40 (always avoid)	3 months
Secondary	Diabetes Distress Scale	Total score range from 28 (low stress) to 168 (high stress)	3 months
Secondary	Hypoglycemia Confidence Scale	Total score from 0 (no confidence) to 36 (very confident)	3 months
Secondary	Clarke Hypoglycemia Awareness	Score range from 0 to 7. If more than 4 : reduced perception, if less : normal perception.	3 months
Secondary	INSPIRE survey	Total score from 0 (high acceptance) to 110 (low acceptance)	3 months
Secondary	System Usability Scale (SUS)	Total score from 0 (low acceptance) to 100 (high acceptance)	3 months
Secondary	Insulin	Total daily insulin (units/kg), Basal: bolus insulin ratio	3 months
Secondary	Weight and Body Mass Index (BMI)		3 months