Efficacy of Closed-loop Insulin Therapy in Adults Prone to Hypoglycemia (DCLP2)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Type 1 Diabetes Mellitus With Hypoglycemia
• Intervention / Treatment: Device: Closed-loop insulin infusion driven by continuous glucose monitoring through an algorithm, in free-life conditions; Device: Continuous Subcutaneous Insulin Infusion and Continuous Glucose Monitoring

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.

• Study Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Eric M RENARD, MD, PhD; Phone Number: +33 467 338 382; Email: e-renard@chu-montpellier.fr
• Study Contact Backup: Name: Jerome PLACE, MSc; Phone Number: +33 467 457 310; Email: jerome.place@umontpellier.fr

Study Locations

• France
  • Caen, France
    • Active, not recruiting
    • University Hospital of Caen
  • Montpellier, France, 34295
    • Recruiting
    • UH Montpellier
    • Contact: ERIC RENARD, MD; Phone Number: +33467338384; Email: e-renard@chu-montpellier.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Closed-Loop Control (CLC); Closed-loop subcutaneous insulin infusion driven by continuous glucose monitoring through an algorithm	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; Other Names: Artificial Pancreas
Active Comparator: Sensor Augmented Pump (SAP); Closed-loop subcutaneous insulin infusion and continuous glucose monitoring manage by patient	Device: 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; Other Names: Sensor Augmented Pump; CSII and CGM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	<2.5 low risk , [2.5-5] medium risk, >5 high risk	3 months
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)	<2.5 low risk , [2.5-5] medium risk, >5 high risk	3 months
HbA1c at 3 months		at 3 months
HbA1c change from baseline to 3 months		3 months
Fear of Hypoglycemia Survey	Total score from 0 (no fear) to 132 (important fear)	3 months
Hyperglycemia Avoidance Scale	Total score from 0 (do not avoid) to 40 (always avoid)	3 months
Diabetes Distress Scale	Total score range from 28 (low stress) to 168 (high stress)	3 months
Hypoglycemia Confidence Scale	Total score from 0 (no confidence) to 36 (very confident)	3 months
Clarke Hypoglycemia Awareness	Score range from 0 to 7. If more than 4 : reduced perception, if less : normal perception.	3 months
INSPIRE survey	Total score from 0 (high acceptance) to 110 (low acceptance)	3 months
System Usability Scale (SUS)	Total score from 0 (low acceptance) to 100 (high acceptance)	3 months
Insulin	Total daily insulin (units/kg), Basal: bolus insulin ratio	3 months
Weight and Body Mass Index (BMI)		3 months

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); University of Virginia; DexCom, Inc.; Tandem Diabetes Care, Inc.
• Investigators: Principal Investigator: Eric M RENARD, MD, PhD, Montpellier University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2020
• Primary Completion (Anticipated): November 3, 2022
• Study Completion (Anticipated): February 3, 2023

Study Registration Dates

• First Submitted: February 3, 2020
• First Submitted That Met QC Criteria: February 10, 2020
• First Posted (Actual): February 12, 2020

Study Record Updates

• Last Update Posted (Actual): December 15, 2021
• Last Update Submitted That Met QC Criteria: December 14, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Hypoglycemia; Type 1 diabetes; Closed-loop insulin infusion
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: RECHMPL19_0351-(7826); 2019-A01906-51 (Registry Identifier: IDRCB); CIV-FR-19-12-031026 (Registry Identifier: EUDAMED); UC4DK108483 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Sharing with NIDDK
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes