Clinical trial NCT04255381: Yale-Harvard Hotel-based Closed-Loop Studies in Children (HY-GRAID)
Official title: Yale-Harvard Hotel-based Closed-Loop Studies in Children (HY-GRAID)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type1 Diabetes
Keywords: type 1 diabetes
artificial pancreas
closed-loop
automated insulin delivery
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Harvard University
First posted: 2020-02-05
Enrollment: 20
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: SIngle arm cohort study
Primary purpose: TREATMENT

Brief summary: The aim of this clinical study is to determine the feasibility, safety, and preliminary effectiveness of the Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP) system in pediatric subjects with type 1 diabetes in an ambulatory semi-supervised environment over a short duration of 3 days and 2 nights, or up to 60 hours.

Detailed description: The artificial pancreas platform employed under study is centered about the following four key innovations: 1) A zone model predictive control strategy that is at the same time very safe with respect to hypoglycemia, and can simultaneously and independently be tuned with respect to its response to hyperglycemia; 2) Zone control with diurnal blood-glucose target zones; 3) Models of insulin-glucose physiology and insulin on board; 4) A system for alarming and notification of impending hypoglycemia and technical malfunctions: the Health Monitoring System. These features have been evaluated in several clinical trials in adults with unannounced meals and exercise.

The proposed study will evaluate enhancements to our previous system tailored for the special needs of pediatric subjects: 1) A control strategy with responses to hyperglycemia and hypoglycemia spanning wide ranges, as is typical with children; 2) The use of time-dependent zones specific for pediatric subjects; 3) The development of models for young children, capturing the greater physiologic variability, and ensuring cautious insulin delivery; 4) remote alarming and notification systems that are useful to parents.

Eligibility criteria: Inclusion Criteria:

1. Age 2- \<18 years; for first cohort(s), subjects will be 12-17 years; additional age brackets will be 8-11 years and then \<8 years
2. Type 1 diabetes for ≥ 1 year duration - the diagnosis of type 1 diabetes will be based on the history of ketosis/ketoacidosis at diagnosis or laboratory evidence of islet-cell auto-immunity
3. A1c level ≤ 10.0%
4. Use of insulin pump and carbohydrate counting for ≥ 3 months
5. Average total daily insulin dose of at least 10 units/day
6. Current or past use of Continuous Glucose Monitoring (CGM) is desirable but NOT required
7. Normal renal function as measured within 6 months of enrollment
8. Normal thyroid function within 6 months of enrollment, or if previously diagnosed with hypothyroidism, documented within 3 months of enrollment
9. Parent/guardian agrees to stay at hotel with subject for duration of hotel phase and has cell phone that can send/receive text messages
10. Subject and participating parent/guardian speak and comprehend English

Exclusion Criteria:

1. Episode of diabetic ketoacidosis (DKA) within 6 months of enrollment
2. Episode of severe hypoglycemia (seizure, loss of consciousness) within 6 months of enrollment
3. Use of medications (other than insulin) known to affect BG levels within 4 weeks of enrollment - examples include systemic glucocorticoids, metformin, pramlintide, liraglutide)
4. Current use of other medications, that in opinion of investigator, would interfere with safety or effectiveness of the study including acetaminophen
5. Medical disorder, that in opinion of investigator, would be contraindication for inclusion; hypothyroidism and celiac disease are NOT exclusion if under good control
6. Female subjects of childbearing potential unwilling to have pregnancy testing
7. Female subject currently pregnant or lactating
8. History of alcohol or drug abuse, documented eating disorder, or inpatient psychiatric treatment within 6 months of enrollment
9. Subject is currently participating in another research study involving an investigational drug or device

Primary outcomes:
measure: Hypoglycemia Safety: Number of Participants With Blood Glucose (BG)) Readings < 50 Milligrams/Deciliter (mg/dL))
timeFrame: 60 hours
measure: Hyperglycemia Safety: Number of Participants With More Than Two Blood Glucose (BG) Readings > 300 mg/dL Longer Than 2 Hour or Any BG 400 > Milligrams/Deciliter (mg/dL))
timeFrame: 60 hours
measure: Blood Ketone Safety: Number of Participants With Blood Ketone Levels > 1.0 mmol/l for Longer Than 2 Hours or Any Ketone Level> 3.0 mmol/l
timeFrame: 60 hours
measure: Safety: Number of Participants Who Experienced an Adverse Event
timeFrame: 60 hours
Secondary outcomes:
measure: Mean Meter and Sensor Glucose Levels Milligram/Deciliter (mg/dL)
timeFrame: 60 hours
measure: Percent Sensor Glucose Time in Range (70-180 mg/dL)
timeFrame: 60 hours
measure: Percent Sensor Glucose Time Below Range (<70 mg/dL)
timeFrame: 60 hours
measure: Percent Sensor Glucose Time Above Range (>180 mg/dL)
timeFrame: 60 hours
measure: Percent Sensor Glucose Time in Hypoglycemia (<60 mg/dL)
timeFrame: 60 hours
measure: Percent Sensor Glucose Time in Hyperglycemia (>250 mg/dL)
timeFrame: 60 hours
measure: Percent Time AP System Active
timeFrame: 60 hours
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
Study officials:
References:
citation: Deshpande S, Weinzimer SA, Gibbons K, Nally LM, Weyman K, Carria L, Zgorski M, Laffel LM, Doyle FJ 3rd, Dassau E. Feasibility and Preliminary Safety of Smartphone-Based Automated Insulin Delivery in Adolescents and Children With Type 1 Diabetes. J Diabetes Sci Technol. 2024 Mar;18(2):363-371. doi: 10.1177/19322968221116384. Epub 2022 Aug 16.