Hybrid Closed-Loop Control With Smart Prandial Insulin Dosing in Type 1 Diabetes

NCT04878120 | Completed Results FDA Device

• 2 other identifiers: 2101124-CDA-2020-948-A-N
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to evaluate the safety and feasibility of a smart bolus calculator that adjusts insulin dosing for meals according to real-time insulin sensitivity (SI) in adolescents with type 1 diabetes (T1D) using a hybrid closed loop (HCL) system during an active week of diabetes camp.

Conditions

Type 1 Diabetes

Keywords

Insulin Sensitivity (SI); Adolescent; Insulin Pump; Continuous Glucose Monitor (CGM); Hybrid Closed Loop (HCL); Diabetes Camp

Outcome Measures

Primary Outcomes (1)

• Low Blood Glucose Index (LBGI)

  LBGI computed from CGM collected in the four hours following the dinner meal. LBGI is a metric quantifying the risk for hypoglycemia (the higher the LBGI, the higher the exposure to/risk of hypoglycemia), calculated based on the following two steps: 1. Transforming each CGM reading in the time-series of length N into a hypoglycemia risk score (rL(i), i=1,...,N) by applying the following transformation: rL(i) = 10 x (1.509 x (log(CGM(i))\^1.084 - 5.381))\^2, if CGM(i) \<=112.5 mg/dL; rL(i) = 0, if CGM(i) \>112.5 mg/dL 2. Averaging the risk scores rL(i), i=1,...,N. The hypoglycemia risk score ranges from 0 for CGM readings \>112.5 mg/dL (no hypoglycemia risk) to 100 for CGM readings =20 mg/dL (maximum hypoglycemia risk); consequently, LBGI can theoretically assume values between 0 and 100 as well. Clinically relevant LBGI thresholds have been defined: 1. LBGI \<2.5: low hypoglycemia risk 2. LBGI in 2.5-5: moderate hypoglycemia risk 3. LBGI \>5: high hypoglycemia risk.

  4 hours (dinner postprandial period); the final metric for each intervention type is obtained as the average over two consecutive camp days (days 1-2 for the first intervention; days 3-4 for the second intervention)

Secondary Outcomes (6)

• Percentage of Time Spent Below 70 mg/dL

  4 hour (dinner postprandial period); average over two consecutive days for each intervention type, as described for primary outcome

• Percentage of Time Spent in 70-180 mg/dL

  4 hour (dinner postprandial period); average over two consecutive days for each intervention type, as described for primary outcome

• Percentage of Time Spent Above 180 mg/dL

  4 hour (dinner postprandial period); average over two consecutive days for each intervention type, as described for primary outcome

• High Blood Glucose Index (HBGI)

  4 hour (dinner postprandial period); average over two consecutive days for each intervention type, as described for primary outcome

• CGM Coefficient of Variation

  4 hour (dinner postprandial period); average over two consecutive days for each intervention type, as described for primary outcome

Study Arms (2)

Standard HCL System - HCL System with Smart Bolus Calculator

OTHER

Use of standard HCL system followed by use of HCL system with smart bolus calculator informed by insulin sensitivity

Device: Standard HCL System; Device: HCL System with Smart Bolus Calculator

HCL System with Smart Bolus Calculator - Standard HCL System

OTHER

Use of HCL system with smart bolus calculator informed by insulin sensitivity followed by use of standard HCL system

Device: Standard HCL System; Device: HCL System with Smart Bolus Calculator

Interventions

Standard HCL System DEVICE

Standard HCL system (USS Virginia)

HCL System with Smart Bolus Calculator - Standard HCL System; Standard HCL System - HCL System with Smart Bolus Calculator

HCL System with Smart Bolus Calculator DEVICE

HCL system (USS Virginia) with smart bolus calculator informed by insulin sensitivity

HCL System with Smart Bolus Calculator - Standard HCL System; Standard HCL System - HCL System with Smart Bolus Calculator

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age ≥12 and \<18 years old at time of consent
• Clinical diagnosis, based on investigator assessment, of T1D for at least one year
• Currently using insulin for at least six months
• Currently using an insulin pump for at least three months
• Currently using a CGM system for at least three months
• Having at least 75% of CGM data over the previous four weeks
• Using insulin parameters such as carbohydrate ratio and correction factors consistently on their pump in order to dose insulin for meals or corrections
• Access to internet and willingness to upload data during the study as needed
• For females, not currently known to be pregnant or breastfeeding
• A negative urine pregnancy test will be required for all females of childbearing potential
• Willingness to suspend use of any personal CGM for the duration of the clinical trial once the study CGM is in use
• Willingness to switch to lispro (Humalog) or aspart (Novolog) if not using already, and to use no other insulin besides lispro (Humalog) or aspart (Novolog) during the study
• Total daily insulin dose (TDD) of at least 10 U/day
• Willingness not to start any non-insulin glucose-lowering agent during the course of the trial (including metformin, GLP-1 agonists, pramlintide, DPP-4 inhibitors, biguanides, sulfonylureas and naturaceuticals)
• Willingness to eat at least 40 grams of carbohydrates per meal

You may not qualify if:

• Hemoglobin A1c \<5% or \>10% if measured at screening or available from historical medical report performed within the last 6 months; in absence of a valid HbA1c measurement, average blood glucose estimated from CGM data to be approximately between 100 and 240 mg/dL
• History of diabetic ketoacidosis (DKA) in the 6 months prior to enrollment
• Severe hypoglycemia resulting in seizure or loss of consciousness in the 6 months prior to enrollment
• Pregnancy or intent to become pregnant during the trial
• Currently breastfeeding or planning to breastfeed
• Currently being treated for a seizure disorder
• Planned surgery during study duration
• History of cardiac arrhythmia (except for benign premature atrial contractions and benign premature ventricular contractions which are permitted)
• Treatment with any non-insulin glucose-lowering agent (metformin, GLP-1 agonists, pramlintide, DPP-4 inhibitors, SGLT-2 inhibitors, biguanides, sulfonylureas and naturaceuticals)
• A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol.
• Use of an insulin delivery mechanism that is not downloadable by the participant or study team
• Known contact with COVID-positive individual within 14 days of any study admission without negative follow-up COVID-19 Polymerase Chain Reaction (PCR) test performed 3-5 days after the date of exposure
• Symptoms of COVID-19 (e.g., fever, shortness of breath, unexpected loss of taste or smell) developed within 14 days of any study admission
• A positive COVID-19 test within 14 days of any study admission or during study admission participation
• Not being fully vaccinated at the time of the first camp admission (according to Center for Disease Control (CDC) guidelines a person is intended to be fully vaccinated after two weeks from either the second dose of the Pfizer or Moderna vaccine, or the single dose of the Johnson \& Johnson vaccine)

Sponsors & Collaborators

• University of Virginia: lead
• Juvenile Diabetes Research Foundation: collaborator

Study Sites (1)

University of Virginia Center for Diabetes Technology

Charlottesville, Virginia, 22902, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Insulin Resistance

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Study was a 4-day randomized crossover camp, with participants crossing from 1st to 2nd intervention at the end of day 2. Protocol imposed meals in days 1-2 to be repeated in days 3-4. However, meal carbohydrate content used for insulin dosing was reduced in days 3-4 because of suspicion of inaccurate carb estimate from the kitchen and to limit hypoglycemia. This led to significant hypoglycemia reduction in days 3-4, independently of the intervention phase, which complicates data interpretation.

Results Point of Contact

• Title: Dr. Chiara Fabris
• Organization: University of Virginia

cf9qe@virginia.edu

4344220240

Study Officials

• Chiara Fabris, PhD

  University of Virginia Center for Diabetes Technology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: May 4, 2021
• First Posted: May 7, 2021
• Study Start: May 14, 2021
• Primary Completion: June 24, 2022
• Study Completion: June 28, 2022
• Last Updated: May 30, 2024
• Results First Posted: May 30, 2024

Record last verified: 2024-05

Locations

US (1)