Fuzzy Logic Automated Insulin Regulation (FLAIR)
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|ClinicalTrials.gov Identifier: NCT03040414|
Recruitment Status : Completed
First Posted : February 2, 2017
Results First Posted : April 20, 2021
Last Update Posted : April 20, 2021
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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.
|Condition or disease||Intervention/treatment||Phase|
|Type 1 Diabetes Mellitus||Device: MedtronicMinimed 670G 3.0 hybrid closed loop system Device: Medtronic Minimed 670G 4.0 AHCL with Guardian Sensor (3) continuous glucose monitoring sensor.||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||126 participants|
|Intervention Model:||Crossover Assignment|
|Intervention Model Description:||Randomized crossover trial with two 12-week crossover periods in auto mode preceded by a run-in phase.|
|Masking:||None (Open Label)|
|Masking Description:||Open label|
|Official Title:||Home Use of MD-Logic Automated Insulin Delivery System: Safety and Efficacy|
|Actual Study Start Date :||June 3, 2019|
|Actual Primary Completion Date :||April 20, 2020|
|Actual Study Completion Date :||April 20, 2020|
Active Comparator: PID Algorithm
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
The components of the intervention are the insulin pump with insulin delivery algorithm (PID).
Experimental: PID + Fuzzy Logic Algorithm
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.
The components of the intervention are the insulin pump with insulin delivery algorithm (PID + Fuzzy Logic) and Guardian Sensor (3).
- Percentage of Time Glucose Levels Were > 180 mg/dL (10.0 mmol/L) From 6 AM to 11:59 PM [ Time Frame: 12 weeks for each arm of the crossover ]Glucose levels based on sensor glucose data
- Non-inferiority for Percent of Time <54 mg/dL (3.0 mmol/L) During the Entire 24-hour Period. [ Time Frame: 12 weeks for each arm of the crossover ]Glucose levels based on sensor glucose data
- Efficacy: CGM Derived Indices: Mean Glucose Only [ Time Frame: 12 weeks for each arm of the crossover ]Continuous Glucose Monitoring derived indices over the first 84 days of each treatment period for 24 hours (excluding time before auto mode is turned on). Glucose levels based on sensor glucose data for Mean glucose.
- Efficacy: CGM Derived Indices [ Time Frame: 12 weeks for each arm of the crossover ]CGM derived indices over the first 84 days of each treatment period for 24 hours. Glucose levels based on sensor glucose data for coefficient of variation; percentage of sensor glucose readings in the range of 70 to 180 mg/dL (3.9-10.0 mmol/L) and 70 to 140 mg/dL (3.9 to 7.8 mmol/L); percentage of sensor glucose readings >180 mg/dL (daytime is a co-primary outcome) and >250 mg/dL (10.0 and 13.9 mmol/L, respectively)
- Efficacy: Amount of Total, Basal and Bolus Daily Insulin Over the First 84 Days of Each Treatment Period [ Time Frame: 12 weeks for each arm of the crossover ]Amount of total, basal, and bolus daily insulin over the first 84 days of each treatment period (excluding time before auto mode is turned on) for 24 hours. Glucose levels based on sensor glucose data. Sum of daytime and nighttime values may not equal total daily values due to rounding.
- Efficacy: HbA1c [ Time Frame: Time Frame: End of crossover period 1 (Week 14 through 20, depending); and end of crossover period 2 (Week 26-32, depending) ]Glycated hemoglobin (HbA1c) was measured at a central laboratory (Advanced Research and Diagnostic Laboratory University of Minnesota, MN, USA) at randomization and at the end of each period by use of an International Federation of Clinical Chemistry and Laboratory Medicine aligned method (Tosoh HPLC Glycohemoglobin Analyzer, Tosoh Medics, San Francisco, CA, USA; coefficient of variation range 1.4 1.9%).
- Efficacy: BMI for Participants Age ≥18 Years [ Time Frame: 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) ]Height and weight. Body mass index (BMI) is a person's weight in kilograms divided by the square of height in meters. BMI is interpreted using standard weight status categories. These categories are the same for men and women of all body types and ages. Below 18.5 : Underweight; 18.5 - 24.9: Normal or Healthy Weight; 25.0 - 29.9: Overweight; 30.0 and Above: Obese.
- Efficacy: BMI Percentile for Participants Age <18 Years [ Time Frame: 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) ]Height and weight based on CDC standards of measurement. Age and gender adjusted.
- Key Safety Outcome 1) Percentage of Time Sensor Glucose Readings Were <54 mg/dL and <70 mg/dL (3.0 and 3.9 mmol/L, Respectively [ Time Frame: 12 weeks for each arm of the crossover ]Glucose levels based on sensor glucose data
- Key Safety Outcome 2) Number of DKA Events [ Time Frame: 12 weeks for each arm of the crossover ]
DKA as defined by the Diabetes Control and Complications Trial (DCCT) and described below:
- Symptoms such as polyuria, polydipsia, nausea, or vomiting;
- Serum ketones >1.5 mmol/L or large/moderate urine ketones;
- Either arterial blood pH <7.30 or venous pH <7.24 or serum bicarbonate <15; and
- Treatment provided in a health care facility
- Key Safety Outcome 3) Number of Severe Hypoglycemia Events [ Time Frame: 12 weeks for each arm of the crossover ]
Severe hypoglycemia event as defined by the Diabetes Control and Complications Trial (DCCT) and described below:
The event required assistance of another person due to altered consciousness, and required another person to actively administer carbohydrate, glucagon, or other resuscitative actions. This means that the participant was impaired cognitively to the point that he/she was unable to treat himself/herself, was unable to verbalize his/ her needs, was incoherent, disoriented, and/or combative, or experienced seizure or loss of consciousness.
- Amount of Total Insulin at Daytime, Nighttime and Post-meal [ Time Frame: 12 weeks for each arm of the crossover ]Based on sensor glucose data
- Human Factors and Diabetes Technology Attitude and Human Factors Questionnaires [ Time Frame: 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) ]Surveys completed by participants. The Glucose Monitoring Satisfaction Survey is 15 items on a 1-5 scale; Total score calculated as mean of all item scores; higher scores indicate greater satisfaction. The Diabetes Distress Scale is 17 items on a 1-6 scale; Total score calculated as mean of all item scores; higher score denotes more distress. The Hypoglycemia Confidence Survey is 8 items on a 1-4 scale; Total score calculated as mean of all item scores; higher score denotes more confidence. The Diabetes Technology Attitudes Survey is 5 items on a 0-4 scale; Total score calculated as sum of all item scores; higher score denotes more satisfaction with diabetes technology. The Adult INSPIRE Survey is 22 items on a 1-5 scale; Total score calculated as mean of all item scores; higher score denotes more satisfaction with AID. The Adolescent INSPIRE Survey is 17 items on a 1-5 scale; Total score calculated as mean of all item scores; higher score denotes more satisfaction with AID.
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|Ages Eligible for Study:||14 Years to 30 Years (Child, Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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).
Individuals meeting any of the following exclusion criteria at screening will be excluded from study participation:
- 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)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03040414
|United States, Connecticut|
|New Haven, Connecticut, United States, 06510|
|United States, Florida|
|University of Florida|
|Gainesville, Florida, United States, 32611|
|United States, Massachusetts|
|Joslin Diabetes Center|
|Boston, Massachusetts, United States, 02215|
|United States, Minnesota|
|International Diabetes Center|
|Saint Louis Park, Minnesota, United States, 55416|
|Kinderkrankenhaus Auf Der Bult|
|Hannover, Germany, 30173|
|Schneider Children's Medical Center of Israel|
|Petah Tikva, Israel, 4920235|
|University of Ljubljana|
|Principal Investigator:||Richard Bergenstal, MD||International Diabetes Center, HealthPartners Institute|
|Principal Investigator:||Moshe Phillip, MD||Schneider Children's Medical Center, Israel|
Documents provided by HealthPartners Institute:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
|Responsible Party:||HealthPartners Institute|
|Other Study ID Numbers:||
UC4DK108611 ( U.S. NIH Grant/Contract )
UC4DK108611 ( U.S. NIH Grant/Contract )
|First Posted:||February 2, 2017 Key Record Dates|
|Results First Posted:||April 20, 2021|
|Last Update Posted:||April 20, 2021|
|Last Verified:||May 2020|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||Yes|
|Device Product Not Approved or Cleared by U.S. FDA:||Yes|
|Product Manufactured in and Exported from the U.S.:||Yes|
Hybrid closed loop
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Endocrine System Diseases
Immune System Diseases