Fuzzy Logic Automated Insulin Regulation

NCT03040414 | Completed Results DMC FDA Device

• 1 other identifier: UC4DK108611
• Study Type: interventional
• Target: 126
• Locations: 4 countries
• Sites: 7

Brief Summary

Adolescents and young adults with type 1 diabetes often have a difficult time achieving good glucose control, which is so important in reducing the risk for diabetes complications. Despite the use of multiple daily injections or insulin pumps and glucose sensors, there is still a need for many individuals to further improve glucose levels without causing low blood glucose levels (hypoglycemia) or adding to the daily burden of living with diabetes. Today an insulin pump can receive glucose readings from a continuous glucose monitor and adjust the insulin delivery in an attempt to keep glucose levels in a more optimal range. These systems are called hybrid closed loop (HCL). This means that much of the insulin delivery is automated, yet the patient still interacts regularly with the system, particularly to help determine the insulin dose to deliver to cover a meal. Results of early studies using HCL systems in adolescents and adults with type 1 diabetes are encouraging. The objective of this study is to compare the efficacy and safety of the automated insulin delivery (AID) system with proportional integral-derivative (PID) algorithm (Minimed 670G 3.0 HCL) to an AID system with combined PID and Fuzzy Logic Algorithm (Minimed 670G 4.0 Advanced Hybrid Closed-Loop (AHCL)). The trial will test the hypothesis that the Minimed AHCL can reduce daytime hyperglycemia, currently the biggest challenge for AID systems, without increasing hypoglycemia. Up to 124 adolescents and young adults (ages 14-\<30) will be recruited to test each system for three months in a randomized crossover trial. Investigators will compare how effective each hybrid closed loop system is at preventing high blood glucose readings during the day. The investigators will also evaluate the safety of each system and how participants adjust to the daily use of the technology.

Conditions

Type 1 Diabetes Mellitus

Keywords

Hybrid closed loop; Closed loop; Artificial pancreas

Outcome Measures

Primary Outcomes (2)

• Percentage of Time Glucose Levels Were > 180 mg/dL (10.0 mmol/L) From 6 AM to 11:59 PM

  Glucose levels based on sensor glucose data

  12 weeks for each arm of the crossover

• Non-inferiority for Percent of Time <54 mg/dL (3.0 mmol/L) During the Entire 24-hour Period.

  Glucose levels based on sensor glucose data

  12 weeks for each arm of the crossover

Secondary Outcomes (9)

• Efficacy: CGM Derived Indices: Mean Glucose Only

  12 weeks for each arm of the crossover

• Efficacy: CGM Derived Indices

  12 weeks for each arm of the crossover

• Efficacy: Amount of Total, Basal and Bolus Daily Insulin Over the First 84 Days of Each Treatment Period

  12 weeks for each arm of the crossover

• Efficacy: HbA1c

  Time Frame: End of crossover period 1 (Week 14 through 20, depending); and end of crossover period 2 (Week 26-32, depending)

• Efficacy: BMI for Participants Age ≥18 Years

  Time Frame: Screening visit, at initiation (Day 0); randomization (Week 2 through 8, depending); end of crossover period 1 (Week 14 through 20, depending); and end of crossover period 2 (Week 26-32, depending)

Other Outcomes (2)

• Amount of Total Insulin at Daytime, Nighttime and Post-meal

  12 weeks for each arm of the crossover

• Human Factors and Diabetes Technology Attitude and Human Factors Questionnaires

  Time Frame: Screening visit, at initiation (Day 0); end of crossover period 1 (Week 14 through 20, depending); and end of crossover period 2 (Week 26-32, depending)

Study Arms (2)

PID Algorithm

ACTIVE COMPARATOR

Participants will receive insulin delivered by the Medtronic Minimed 670G 3.0 HCL system using a PID algorithm..

Device: MedtronicMinimed 670G 3.0 hybrid closed loop system

PID + Fuzzy Logic Algorithm

EXPERIMENTAL

Participants will receive insulin delivered by the Medtronic advanced hybrid closed loop system (Minimed 670G 4.0 AHCL) with Guardian Sensor (3) continuous glucose monitoring sensor.

Device: Medtronic Minimed 670G 4.0 AHCL with Guardian Sensor (3) continuous glucose monitoring sensor.

Interventions

MedtronicMinimed 670G 3.0 hybrid closed loop system DEVICE

The components of the intervention are the insulin pump with insulin delivery algorithm (PID).

PID Algorithm

Medtronic Minimed 670G 4.0 AHCL with Guardian Sensor (3) continuous glucose monitoring sensor. DEVICE

The components of the intervention are the insulin pump with insulin delivery algorithm (PID + Fuzzy Logic) and Guardian Sensor (3).

PID + Fuzzy Logic Algorithm

Eligibility Criteria

• Age: 14 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Type 1 diabetes mellitus (as diagnosed clinically) for at least one year
• Age 14-\<30 years at enrollment
• For females, not currently known to be pregnant, be breast-feeding or planning to become pregnant within the study duration.
• Using an insulin pump or multiple daily injections of insulin
• Participant must be able to obtain U-100 rapid acting insulin analogues, Aspart or Lispro, for use during the study (since these are the only insulins approved for the study pump and the study is not supplying insulin)
• MDI users must be on a basal/bolus regimen
• Participants must have a minimum total daily dose (TDD) of at least eight units
• HbA1c from an approved HbA1c point of care analyzer with a value 7.0%-11.0%
• Willingness or ability to do carbohydrate counting
• In the investigator's judgment, able to understand and likely to be adherent to the protocol
• For subjects \<18 years old, living with one or more diabetes care partners (eg.g. parent/legal guardian), of whom at least one is committed to participating in study training for emergency procedures for severe hypoglycemia and able to contact the participant in case of an emergency.
• Have adequate internet access and a computer system that meets requirements for uploading data.
• For participants currently using CGM or insulin pump, willingness to discontinue personal CGM and pump when using the study CGM and pumps (note: including implantable CGMs).

You may not qualify if:

• Concomitant disease that influences metabolic control or HbA1c interpretation (e.g. anemia, significantly impaired hepatic function, confirmed gastroparesis, renal failure, history of adrenal insufficiency, sickle cell disease, haemoglobinopathy, or has received red blood cell transfusion or erythropoietin within three months prior to time of screening) or other medical condition which, in the Investigator's opinion, may compromise patient safety, affect outcome assessments, or affect the participant's ability to follow the protocol
• Oral or parenteral glucocorticoids taken within 1 month prior to enrollment, or plans to take oral or parenteral glucocorticoids within the planned study duration. Exceptions: Short term oral or parenteral glucocorticoids up to seven days
• Use of antidiabetic agents other than insulin
• Use of other medications, which in the judgment of the investigator would be a contraindication to participation in the study
• One or more episodes of severe hypoglycemia (hypoglycemia requiring treatment by another person) within the previous six months
• Known allergy to medical grade adhesives
• Participation in another study of a medical device or drug that could affect glucose measurements or glucose management or receipt of any investigational medical product within 1 month prior to enrollment
• Current eating disorder such as anorexia or bulimia
• Currently abusing illicit drugs, marijuana, prescription drugs, or alcohol
• Visual impairment or hearing loss, which may compromise the participant's ability to perform all study procedures safely, as determined by the investigator
• One or more episodes of diabetic ketoacidosis (DKA) requiring hospitalization within six months prior to screening
• Working night shifts
• Untreated celiac disease, hyperthyroidism, or hypothyroidism
• Clinically significant nephropathy (eGFR \<45 mL/min) or on dialysis. Creatinine to determine eGFR must have been obtained as part of usual care within 12 months prior to enrollment (if not available, at time of enrollment, screening can proceed but it must be available prior to randomization)

Sponsors & Collaborators

• HealthPartners Institute: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Medtronic: collaborator
• Jaeb Center for Health Research: collaborator
• Schneider Children's Medical Center, Israel: collaborator
• University of Ljubljana: collaborator
• Yale University: collaborator
• Joslin Diabetes Center: collaborator
• University of Florida: collaborator
• Stanford University: collaborator
• International Diabetes Center at Park Nicollet: collaborator
• Kinderkrankenhaus auf der Bult: collaborator
• University of Minnesota: collaborator

Study Sites (7)

Yale University

New Haven, Connecticut, 06510, United States

Location

University of Florida

Gainesville, Florida, 32611, United States

Location

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

International Diabetes Center

Saint Louis Park, Minnesota, 55416, United States

Location

Kinderkrankenhaus Auf Der Bult

Hanover, 30173, Germany

Location

Schneider Children's Medical Center of Israel

Petah Tikva, 4920235, Israel

Location

University of Ljubljana

Ljubljana, Slovenia

Location

Related Publications (11)

• Bergenstal RM, Tamborlane WV, Ahmann A, Buse JB, Dailey G, Davis SN, Joyce C, Peoples T, Perkins BA, Welsh JB, Willi SM, Wood MA; STAR 3 Study Group. Effectiveness of sensor-augmented insulin-pump therapy in type 1 diabetes. N Engl J Med. 2010 Jul 22;363(4):311-20. doi: 10.1056/NEJMoa1002853. Epub 2010 Jun 29.

  PMID: 20587585 BACKGROUND

• Phillip M, Battelino T, Atlas E, Kordonouri O, Bratina N, Miller S, Biester T, Stefanija MA, Muller I, Nimri R, Danne T. Nocturnal glucose control with an artificial pancreas at a diabetes camp. N Engl J Med. 2013 Feb 28;368(9):824-33. doi: 10.1056/NEJMoa1206881.

  PMID: 23445093 BACKGROUND

• Bergenstal RM, Klonoff DC, Garg SK, Bode BW, Meredith M, Slover RH, Ahmann AJ, Welsh JB, Lee SW, Kaufman FR; ASPIRE In-Home Study Group. Threshold-based insulin-pump interruption for reduction of hypoglycemia. N Engl J Med. 2013 Jul 18;369(3):224-32. doi: 10.1056/NEJMoa1303576. Epub 2013 Jun 22.

  PMID: 23789889 BACKGROUND

• Nimri R, Muller I, Atlas E, Miller S, Fogel A, Bratina N, Kordonouri O, Battelino T, Danne T, Phillip M. MD-Logic overnight control for 6 weeks of home use in patients with type 1 diabetes: randomized crossover trial. Diabetes Care. 2014 Nov;37(11):3025-32. doi: 10.2337/dc14-0835. Epub 2014 Jul 30.

  PMID: 25078901 BACKGROUND

• Nimri R, Phillip M. Artificial pancreas: fuzzy logic and control of glycemia. Curr Opin Endocrinol Diabetes Obes. 2014 Aug;21(4):251-6. doi: 10.1097/MED.0000000000000073.

  PMID: 24937038 BACKGROUND

• Nimri R, Muller I, Atlas E, Miller S, Kordonouri O, Bratina N, Tsioli C, Stefanija MA, Danne T, Battelino T, Phillip M. Night glucose control with MD-Logic artificial pancreas in home setting: a single blind, randomized crossover trial-interim analysis. Pediatr Diabetes. 2014 Mar;15(2):91-9. doi: 10.1111/pedi.12071. Epub 2013 Aug 15.

  PMID: 23944875 BACKGROUND

• Bergenstal RM, Garg S, Weinzimer SA, Buckingham BA, Bode BW, Tamborlane WV, Kaufman FR. Safety of a Hybrid Closed-Loop Insulin Delivery System in Patients With Type 1 Diabetes. JAMA. 2016 Oct 4;316(13):1407-1408. doi: 10.1001/jama.2016.11708. No abstract available.

  PMID: 27629148 BACKGROUND

• Nimri R, Bratina N, Kordonouri O, Avbelj Stefanija M, Fath M, Biester T, Muller I, Atlas E, Miller S, Fogel A, Phillip M, Danne T, Battelino T. MD-Logic overnight type 1 diabetes control in home settings: A multicentre, multinational, single blind randomized trial. Diabetes Obes Metab. 2017 Apr;19(4):553-561. doi: 10.1111/dom.12852. Epub 2017 Jan 19.

  PMID: 27981804 BACKGROUND

• Dovc K, Battelino T, Beck RW, Sibayan J, Bailey RJ, Calhoun P, Turcotte C, Weinzimer S, Smigoc Schweiger D, Nimri R, Bergenstal RM. Impact of Temporary Glycemic Target Use in the Hybrid and Advanced Hybrid Closed-Loop Systems. Diabetes Technol Ther. 2022 Nov;24(11):848-852. doi: 10.1089/dia.2022.0153. Epub 2022 Aug 9.

  PMID: 35848991 DERIVED

• Hood KK, Laffel LM, Danne T, Nimri R, Weinzimer SA, Sibayan J, Bailey RJ, Schatz D, Bratina N, Bello R, Punel A, Calhoun P, Beck RW, Bergenstal RM, Phillip M. Lived Experience of Advanced Hybrid Closed-Loop Versus Hybrid Closed-Loop: Patient-Reported Outcomes and Perspectives. Diabetes Technol Ther. 2021 Dec;23(12):857-861. doi: 10.1089/dia.2021.0153. Epub 2021 Oct 26.

  PMID: 34270328 DERIVED

• Bergenstal RM, Nimri R, Beck RW, Criego A, Laffel L, Schatz D, Battelino T, Danne T, Weinzimer SA, Sibayan J, Johnson ML, Bailey RJ, Calhoun P, Carlson A, Isganaitis E, Bello R, Albanese-O'Neill A, Dovc K, Biester T, Weyman K, Hood K, Phillip M; FLAIR Study Group. A comparison of two hybrid closed-loop systems in adolescents and young adults with type 1 diabetes (FLAIR): a multicentre, randomised, crossover trial. Lancet. 2021 Jan 16;397(10270):208-219. doi: 10.1016/S0140-6736(20)32514-9.

  PMID: 33453783 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Amy Becker LaFrance, Sr. Manager, Research Project Management Office
• Organization: HealthPartners Institute

Amy.B.LaFrance@healthpartners.com

952.967.5079

Study Officials

• Richard Bergenstal, MD

  International Diabetes Center, HealthPartners Institute

  PRINCIPAL INVESTIGATOR

• Moshe Phillip, MD

  Schneider Children's Medical Center, Israel

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open label
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized crossover trial with two 12-week crossover periods in auto mode preceded by a run-in phase.

Study Record Dates

• First Submitted: January 31, 2017
• First Posted: February 2, 2017
• Study Start: June 3, 2019
• Primary Completion: April 20, 2020
• Study Completion: April 20, 2020
• Last Updated: April 20, 2021
• Results First Posted: April 20, 2021

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1); DE (1); SL (1); US (4)