Study of MiniMed™ 640G Insulin Pump With SmartGuard™ in Prevention of Low Glucose Events in Adults With Type 1 Diabetes (SMILE)

A premarket, international multicenter, prospective, open label, adaptive, randomized controlled study.

The aim is to evaluate the efficacy of sensor augmented pump therapy with MiniMed™640G and SmartGuard™in preventing hypoglycemic events in comparison with continuous subcutaneous insulin infusion therapy in type 1 diabetes adults with an increased risk of hypoglycemia. The primary objective is to demonstrate a reduction in the mean number of hypoglycemic events when using the MiniMed™640G system with SmartGuard™ and the secondary objectives will aim at evaluating the difference in glycemic parameters and HbA1c.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Device: MiniMed™640G and Suspend before low; Device: MiniMed™640G

• Study Type: Interventional
• Enrollment (Actual): 153
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Besançon, France
    • CHU de Besancon
  • Grenoble, France
    • CHU Grenoble
  • Marseille, France
    • APHM - La Conception
  • Montpellier, France
    • CHU Montpellier - Hôpital Lapeyronie
• Italy
  • Bergamo, Italy
    • Ospedale Papa Giovanni XXIII
  • Milan, Italy
    • Ospedale S. Raffaele
  • Olbia, Italy
    • Ospedale S. Gionanni di Dio
• Netherlands
  • Gouda, Netherlands
    • Groene Hart Ziekenhuis
  • Rotterdam, Netherlands
    • Maasstad Ziekenhuis
  • Utrecht, Netherlands
    • UMC Utrecht
  • Zwolle, Netherlands
    • Isala
• United Kingdom
  • London, United Kingdom, SE5 9NU
    • King's College London
  • Manchester, United Kingdom
    • Manchester Diabetes Center
  • N. Yorkshire
    • Harrogate, N. Yorkshire, United Kingdom, HG2 7SX
      • Harrogate District Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 24 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 24-75 years old at time of screening.
• Diagnosed with Type 1 diabetes ≥10 years prior to screening.
• On pump therapy for ≥ 6 months prior to screening.
• Not on Real Time continuous glucose monitoring for ≥ 3 months prior to screening.
• HbA1c value ≥5.8% and ≤10.0% as assessed by local lab ≤ 15 days prior to screening or performed at screening.
• A documented Severe Hypoglycemia event ≤ 12 months prior to screening, OR Clarke score ≥4 assessed at time of screening, OR
• Gold score ≥4 assessed at time of screening.
• Subject is willing to sign and date informed consent, comply with all study procedures and wear all study devices as required during the study.

Exclusion Criteria:

• Untreated Addison's disease, thyroid disorder, growth hormone deficiency, hypopituitarism or definite gastroparesis, per investigator judgment.
• Subject is using Pramlintide (Symlin) SGLT2 inhibitor, GLP agonist at time of screening.
• Renal failure defined by creatinine clearance <30 ml/min, as assessed by local lab test ≤ 3 months before screening or performed at screening at local lab.
• Hearing or vision impairment hindering perception of glucose display and alarms, or otherwise incapable of using the study devices, per investigator judgment.
• Current pregnancy or intention to conceive.
• Any unresolved adverse skin condition in the area of sensor placement (e.g. psoriasis, rash, Staphylococcus infection).
• Alcohol or drug abuse, other than nicotine, per investigator judgment.
• Any other disease or condition that may preclude the patient from participating in the study, per investigator judgment.
• Legally incompetent, illiterate or vulnerable person.

Randomization Criteria:

• If subjects meet the above criteria, as well as all of the following criteria assessed at the end of the run-in period, they may continue to participate in the treatment period of the study:

  • Subject has worn two weeks the sensor with transmitter during the run-in period.
  • Subject has shown acceptable tolerance of sensor wear, per investigator judgment.
  • Subject performed ≥ 4 finger stick blood glucose measurements daily, as determined by CareLink™ Clinical data upload as the mean number of SMBG/day over the past 14 days (SMBG number / day ≥ 3.5 rounds up to 4).
  • Subject showed ability to comprehend the pump training and study procedures, per investigator judgment.

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: Treatment; MiniMed™640G and Suspend before Low feature of SmartGuard™ turned on.	Device: MiniMed™640G and Suspend before low; All enrolled subjects will start a run in phase, receive training and start pump therapy with the MiniMed™640G insulin pump and usage of blinded Continuous Glucose Monitoring. Eligible subjects that meet the randomization criteria assessed after the running phase will be randomized into the treatment or control arm. Treatment Arm: training and start of Sensor Augmented Pump therapy with Suspend before Low feature of SmartGuard turned ON. Control Arm: continuation of pump therapy alone with blinded continuous glucose monitoring for a total of 6 weeks during the treatment phase.; Other Names: MiniMed™640G and SmartGuard™; MiniMed™640G and Predictive Low Glucose Management
Active Comparator: Control; MiniMed™640G alone	Device: MiniMed™640G; Control Arm: continuation of pump therapy alone with blinded continuous glucose monitoring for a total of 6 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean Number of Sensor Glucose Hypoglycaemic Events Below or Equal to 55 mg/dL Per Patient/Week.	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean Time Spent of Sensor Glucose Values Below or Equal 55 mg/dL.	6 months
Mean Time Spent of Sensor Glucose Values Within Range and Including 70-180 mg/dL.	6 months

Collaborators and Investigators

• Sponsor: Medtronic Diabetes

Publications and helpful links

General Publications

• Habteab A, Castaneda J, de Valk H, Choudhary P, Bosi E, Lablanche S, de Portu S, Da Silva J, Vorrink-de Groot L, Shin J, Cohen O. Predicting Factors Associated with Hypoglycemia Reduction with Automated Predictive Insulin Suspension in Patients at High Risk of Severe Hypoglycemia: An Analysis from the SMILE Randomized Trial. Diabetes Technol Ther. 2020 Sep;22(9):681-685. doi: 10.1089/dia.2019.0495.
• Bosi E, Choudhary P, de Valk HW, Lablanche S, Castaneda J, de Portu S, Da Silva J, Re R, Vorrink-de Groot L, Shin J, Kaufman FR, Cohen O; SMILE Study Group. Efficacy and safety of suspend-before-low insulin pump technology in hypoglycaemia-prone adults with type 1 diabetes (SMILE): an open-label randomised controlled trial. Lancet Diabetes Endocrinol. 2019 Jun;7(6):462-472. doi: 10.1016/S2213-8587(19)30150-0. Epub 2019 Apr 29.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): October 1, 2018
• Study Completion (Actual): October 1, 2018

Study Registration Dates

• First Submitted: March 29, 2016
• First Submitted That Met QC Criteria: April 5, 2016
• First Posted (Estimate): April 12, 2016

Study Record Updates

• Last Update Posted (Actual): January 21, 2020
• Last Update Submitted That Met QC Criteria: January 10, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: CEP311

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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