Yale-Harvard Hotel-based Closed-Loop Studies in Children (HY-GRAID) (HY-GRAID)

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.

Study Overview

• Status: Completed
• Conditions: Type1 Diabetes
• Intervention / Treatment: Device: Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP)

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP); Use Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP) system	Device: Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP); Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypoglycemia Safety: Number of Participants With Blood Glucose (BG)) Readings < 50 Milligrams/Deciliter (mg/dL))	Number of participants with more than one confirmed BG < 50 mg/dL	60 hours
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))	No more than two confirmed BG ≥ 300 mg/dL longer than 2 hours, and no BG ≥ 400 mg/dL, unless determined to be from an infusion site failure.	60 hours
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	Number of participants with blood ketone level > 1.0 mmol/l for longer than 2 hours, and no blood ketone level >3.0 mmol/L, unless determined to be from an infusion site. failure	60 hours
Safety: Number of Participants Who Experienced an Adverse Event	Adverse events include seizure, loss of consciousness, severe hypoglycemia, diabetic ketoacidosis	60 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Meter and Sensor Glucose Levels Milligram/Deciliter (mg/dL)	Mean meter and sensor glucose levels (mg/dL)	60 hours
Percent Sensor Glucose Time in Range (70-180 mg/dL)	Percentage of time, over the whole evaluation period, during which the glucose level, as determined by the continuous glucose sensor, is between 70-180 mg/dL	60 hours
Percent Sensor Glucose Time Below Range (<70 mg/dL)	Percentage of time, over the whole evaluation period, during which the glucose level, as determined by the continuous glucose sensor, is below 70 mg/dL	60 hours
Percent Sensor Glucose Time Above Range (>180 mg/dL)	Percentage of time, over the whole evaluation period, during which the glucose level, as determined by the continuous glucose sensor, is greater than 180 mg/dL	60 hours
Percent Sensor Glucose Time in Hypoglycemia (<60 mg/dL)	Percentage of time, over the whole evaluation period, during which the glucose level, as determined by the continuous glucose sensor, is below 60 mg/dL	60 hours
Percent Sensor Glucose Time in Hyperglycemia (>250 mg/dL)	Percentage of time, over the whole evaluation period, during which the glucose level, as determined by the continuous glucose sensor, is greater than 250 mg/dL	60 hours
Percent Time AP System Active	Percentage of time, over the whole evaluation period, during which the sensor and pump are determined to be wirelessly connected and communicating with each other, based on duration of alert and error messages indicated by the system	60 hours

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: Harvard University

Publications and helpful links

General Publications

• 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. 2022 Aug 16:19322968221116384. doi: 10.1177/19322968221116384. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2018
• Primary Completion (ACTUAL): December 31, 2020
• Study Completion (ACTUAL): December 31, 2020

Study Registration Dates

• First Submitted: January 29, 2020
• First Submitted That Met QC Criteria: February 3, 2020
• First Posted (ACTUAL): February 5, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 1, 2022
• Last Update Submitted That Met QC Criteria: May 11, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: artificial pancreas; closed-loop; type 1 diabetes; automated insulin delivery
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Gastrointestinal Agents; Pancrelipase
• Other Study ID Numbers: 1609018413

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