Safety Evaluation of the Hybrid Closed Loop (HCL) System in Pediatric Subjects With Type 1 Diabetes

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02660827

Enrollment

151

Registered

2016-01-21

Start date

2016-04-18

Completion date

2021-02-01

Last updated

2022-01-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Type 1 Diabetes

Brief summary

This study is a single-arm, multi-center, Home and Hotel Clinical Investigation in pediatric subjects with type 1 diabetes on insulin pump therapy. The purpose of this study is to demonstrate that the closed loop algorithm is safe as part of the overall system, and to assess the PLGM feature in 7-13 years old subjects.

Detailed description

The study will proceed as follows: Run-in Period - General: A total of up to 200 subjects (age 2-13) will be enrolled at up to 15 investigational centers (14 in the US, 1 EMEA) in order to reach 120 subjects who will complete the HCL study. Study Period - At Home: Following the two week run-in period using the Study Pump (670G), all subjects (age 2-13) will participate in a 3-month study period. Study Period - Hotel Study Subjects (age 7-13) will participate in a Hotel study (6 days, 5 nights), with the remainder of the study period to be spent at home. Subjects 2-6 years of age are not required to participate in a hotel study. Instead, they will participate in an out-of-home study for 5 consecutive days, 4-6 hours per day. Continued Access Program Subjects will be given the opportunity to extend use of their study devices for a period of up to 3 years . If subjects choose to participate in the continuation period, they will retain the study devices at the end of study period visit or receive them back in the event they have been returned to study staff already.

Interventions

DEVICEInsulin Pump

Closed Loop Algorithm

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

2 Years to 13 Years

Healthy volunteers

Inclusion criteria

General Inclusion Criteria 1. Subject is age 2-13 years at time of screening 2. Subject has a clinical diagnosis of type 1 diabetes for 1 year or more as determined via medical record or source documentation by an individual qualified to make a medical diagnosis 3. Subject age 2-6 years has a clinical diagnosis of type 1 diabetes for 3 months or more as determined via medical record or source documentation by an individual qualified to make a medical diagnosis Study-specific inclusion criteria 4. Subject must have a minimum daily insulin requirement (Total Daily Dose) of greater than or equal to 8 units 5. Subjects 7-13: Subjects and their parent(s)/guardian(s) are willing to participate in an overnight visit at the end of the run-in period. 6. Subject 7-13 years of age and their parent(s)/guardian(s) are willing to participate in a hotel study for the specified duration of hotel stay. 7. Subject 2-6 years of age and their parent(s)/guardian(s) are willing to participate in an extended visit during the study period to perform Frequent Sample Testing. 8. Subject must have companion 18 years or older who will sleep in the same dwelling place every night during the study period. This requirement may be verified by subject report at screening visit. 9. Subject is willing to perform ≥ 4 finger stick blood glucose measurements daily 10. Subject is willing to perform required sensor calibrations 11. Subject is willing to wear the system continuously throughout the study 12. Subject has a Glycosylated hemoglobin (A1C) value less than 10.0% (as processed by Central Lab) at time of screening visit Note: All HbA1C blood specimens will be sent to and tested by a NGSP certified Central Laboratory. A1C testing must follow National Glycohemoglobin Standardization Program (NGSP) standards. 13. Subject has TSH in the normal range OR if the TSH is out of normal reference range the Free T3 is below or within the lab's reference range and Free T4 is within the normal reference range. 14. Subject 7 -13 years of age has had pump therapy for greater than 6 months prior to screening (with or without CGM experience) 15. Subject 2-6 years of age has had pump therapy for greater than 90 days prior to screening (with or without CGM experience) 16. Subjects and their parent(s)/guardian(s) are willing to upload data from the study pump; must have Internet access and a computer system that meets the requirements for uploading the study pump 17. If subject has celiac disease, it has been adequately treated as determined by the investigator 18. Subjects and their parent(s)/guardian(s) are willing to take one of the following insulins and can financially support the use of either of the 2 insulin preparations throughout the course of the study (i.e. co-payments for insulin with insurance or able to pay full amount) * Humalog® (insulin lispro injection) * NovoLog® (insulin aspart) 19. Subjects and their parent(s)/guardian(s)/companions must be able to speak and be literate in English as verified by the investigator

Exclusion criteria

1. Subject has a history of 2 or more episodes of severe hypoglycemia, which resulted in any the following during the 6 months prior to screening: 1. Medical assistance (i.e. Paramedics, Emergency Room ( ER) or Hospitalization) 2. Coma 3. Seizures 2. Subject is unable to tolerate tape adhesive in the area of sensor placement 3. Subject has any unresolved adverse skin condition in the area of sensor placement (e.g., psoriasis, dermatitis herpetiformis, rash, Staphylococcus infection) 4. Females who are sexually active and able to conceive will be excluded if they are not using an effective method of contraception and do not agree to continue using an effective method of contraception for the duration of the study as determined by investigator. 5. Subject has a cardiovascular condition which the investigator determines should exclude the subject, i.e. ventricular rhythm disturbance, hypertrophic cardiomyopathy 6. Subject is being treated for hyperthyroidism at time of screening 7. Subject has diagnosis of adrenal insufficiency 8. Subject 7-13 years of age has had DKA in the 6 months prior to screening visit. 9. Subject 2-6 years of age has had DKA in the 3 months prior to screening visit 10. Subject has taken any oral, injectable, or intravenous (IV) glucocorticoids within 8 weeks from time of screening visit, or plans to take any oral, injectable, or IV glucocorticoids during the course of the study 11. Subject is actively participating in an investigational study (drug or device) wherein he/she has received treatment from an investigational study drug or investigational study device in the last 2 weeks 12. Subject 7-13 years of age has been hospitalized or has visited the ER in the 6 months prior to screening resulting in a primary diagnosis of uncontrolled diabetes 13. Subject 2-6 years of age has been hospitalized or has visited the ER in the 3 months prior to screening resulting in a primary diagnosis of uncontrolled diabetes 14. Subject is currently abusing illicit drugs 15. Subject is currently abusing marijuana. 16. Subject is currently abusing prescription drugs 17. Subject is currently abusing alcohol 18. Subject is using pramlintide (Symlin), DPP-4 inhibitor, liraglutide (Victoza or other GLP-1 agonists), metformin, canagliflozin (Invokana or other SGLT2 inhibitors) at time of screening 19. Subject has a history of visual impairment which would not allow subject to participate in the study and perform all study procedures safely, as determined by the investigator 20. Subject has elective surgery planned that requires general anesthesia during the course of the study 21. Subject has a sickle cell disease, hemoglobinopathy; or has received red blood cell transfusion or erythropoietin within 3 months prior to time of screening 22. Subject plans to receive red blood cell transfusion or erythropoietin over the course of study participation 23. Subject diagnosed with current eating disorder such as anorexia or bulimia 24. Subject has been diagnosed with chronic kidney disease that results in chronic anemia 25. Subject has a hematocrit that is below the normal reference range of lab used. 26. Subject is on dialysis 27. Subject has serum creatinine of \>2 mg/dL.

Design outcomes

Primary

Measure	Time frame	Description
Age 2-13 Years Old Subjects Change in A1C	Baseline and end of 3-month study period	Descriptive analysis of change in A1C from baseline to end of 3-month study period

Secondary

Measure	Time frame	Description
Age 2-13 Years Old Subjects Mean Change in % of Time in Hyperglycemia (> 180 mg/dL)	baseline and 3 months	mean change in % of time in hyperglycemia (\> 180 mg/dL) from baseline to 3 months study period
Age 2-13 Years Old Subjects Mean Change in % of Time in Hypoglycemia (<70 mg/dL)	baseline and 3 months	mean change in % of time in hypoglycemia (\< 70 mg/dL) from baseline to 3 months study period
Age 2-13 Years Old Subjects Mean Change in % of Time in Euglycemia (70-180 mg/dL)	baseline and 3 months	mean change in % of time in Euglycemia (70-180 mg/dL) from baseline to 3 months study period
Age 2-13 Years Old - Number of Diabetic Ketoacidosis (DKA) Event	3 months	Number of Diabetic Ketoacidosis (DKA) events occurred during 3-month study period.
Age 7-13 Years Old Subjects PLGM Performance - Event Rate Without Hypoglycemia at YSI-FST <=65 mg/dL	Up to 12 hours after the start of PLGM period	Event rate without Hypoglycemia at YSI-FST \<=65 mg/dL among 105 subjects who underwent the PLGM experiments. The event rate without hypoglycemia is the number of experiments without hypoglycemia/total number of experiments and hypoglycemic events are defined based on the occurrence of 2 or more continuous YSI-FST \<= 65mg/dL during in-clinic procedures.
Age 2-13 Years Old - Number of Severe Hypoglycemic Event	3 months	Number of severe hypoglycemic events occurred during 3-month study period.

Countries

Israel, United States

Participant flow

Recruitment details

151 subjects aged 2-13 years entered study period, 1 subject withdrawn during study period, 5 subjects didn't participate continued access period after finishing study period; 145 subjects aged 2-13 years entered continued access period, 25 subjects withdrawn and 120 subjects completed continued access period.

Pre-assignment details

2-13 years subjects wearing MMT-670G insulin pump

Participants by arm

Arm	Count
Age 2-13 Yrs Age 2-13 Yrs Subjects wearing MMT- 670G insulin pump	151
Total	151

Withdrawals & dropouts

Period	Reason	FG000
From Study to End of Continued Access	Adverse Event	3
From Study to End of Continued Access	didn't participate continued access period	5
From Study to End of Continued Access	Withdrawal by Sponsor	2
From Study to End of Continued Access	Withdrawal by Subject	21
Period 1: Study Period	Withdrawal by Subject	1
Period 2: Continued Access Period	Adverse Event	3
Period 2: Continued Access Period	Withdrawal by Sponsor	2
Period 2: Continued Access Period	Withdrawal by Subject	20

Baseline characteristics

Characteristic	Age 2-13 Yrs
Age, Continuous	8.9 years STANDARD_DEVIATION 3.3
BMI (kg/m2)	18.4 kg/m^2 STANDARD_DEVIATION 3.8
Race (NIH/OMB) American Indian or Alaska Native	1 Participants
Race (NIH/OMB) Asian	2 Participants
Race (NIH/OMB) Black or African American	5 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	11 Participants
Race (NIH/OMB) White	132 Participants
Region of Enrollment Israel	11 participants
Region of Enrollment United States	140 participants
Sex: Female, Male Female	69 Participants
Sex: Female, Male Male	82 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 151	0 / 145
other Total, other adverse events	88 / 151	113 / 145
serious Total, serious adverse events	0 / 151	4 / 145

Outcome results

Primary

Age 2-13 Years Old Subjects Change in A1C

Descriptive analysis of change in A1C from baseline to end of 3-month study period

Time frame: Baseline and end of 3-month study period

Population: 2-13 years old subjects wearing MMT-670G insulin pump; two subjects end of study A1C not collected.

Arm	Measure	Value (MEAN)	Dispersion
Age 2-13 Years Old Wearing MMT-670G Insulin Pump	Age 2-13 Years Old Subjects Change in A1C	-0.37 percentage of hemoglobin	Standard Deviation 0.62

Secondary