Efficacy and Safety of an Artificial-pancreas-like Learning-based Control in Type 1 Diabetes on Multiple Daily Injection Therapy (ELITE)

Efficacy and Safety of an Artificial-pancreas-like Learning-based Control in Type 1 Diabetes on Multiple Daily Injection Therapy: Protocol of a Multi-center, Non-inferiority, Randomized Controlled Trial (ELITE Study)

This study is designed as a blinded, multi-center, non-inferiority randomized controlled clinical trial. It aims to enroll hospitalized T1D diabetes patients, ensuring an equal distribution with a 1:1 ratio between the intervention and control groups. The trial is set to take place across three locations in China: Peking University People's Hospital, Hebei Provincial People's Hospital, and Xingtai People's Hospital. Before participating, all subjects are required to provide their consent by signing a written informed consent form. Within the framework of the trial, the intervention group will receive insulin dosage recommendations from AP-A, subject to approval by a physician, whereas the control group will be treated with insulin dosages according to the current clinical guidelines established by their physicians.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Device: AP-A Dosage Decision Support System

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntary signing of an informed consent form.
2. Age between 18 and 70 years, with a T1D diagnosis of at least one year.
3. A confirmed diagnosis of T1D diabetes by at least two endocrinologists and fulfillment of at least one of the following conditions: a) Fasting C-peptide level less than 0.3 ng/mL. b) Fasting C-peptide level between 0.3 ng/mL and 0.6 ng/mL with at least one positive diabetic autoantibody.
4. Receiving intensified treatment regimen with multiple daily subcutaneous insulin injections upon screening and during the whole study period.

Exclusion Criteria:

1. Conditions such as diabetic ketoacidosis, diabetic ketosis, hyperglycemic hyperosmolar state, or other acute complications related to diabetes.
2. The presence of concurrent fever, severe infections, acute abdominal conditions, uncontrolled thyroid dysfunction, or the acute phase of any organ system disease.
3. A history within the last 3 months of serious cardiovascular issues including decompensated heart failure (NYHA Class III or IV), myocardial infarction, coronary artery bypass grafting, or coronary stent implantation, as well as uncontrolled severe arrhythmias or ischemic or hemorrhagic stroke.
4. Laboratory test abnormalities that exceed certain thresholds, such as alanine transaminase or aspartate transaminase levels greater than three times the upper limit of normal, total bilirubin levels more than twice the upper limit of normal, hemoglobin levels below 100 g/L, albumin levels below 30 g/L, or an estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73m².
5. Individuals who are required to fast or are unable to eat normally due to special circumstances.
6. Pregnant or breastfeeding women.
7. Individuals suffering from psychiatric illnesses or other cognitive impairments that may affect their ability to participate in the study.
8. Participants who are unable to wear a CGM due to severe allergies, skin diseases, or conditions at the sensor site such as lesions, scarring, redness, infection, or edema, which could interfere with the sensor's adhesion or the accuracy of glucose measurements in the interstitial fluid.
9. The systemic use of corticosteroids within the last month, with the exception of inhaled or topical steroids.
10. Any other condition or reason that the researcher deems to make the participant unsuitable for inclusion in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AP-A Dosage Decision Support System; The AP-A Dosage Decision Support System represents a new solution in diabetes care, offering customized insulin dosage recommendations to patients. This system is a product of integrating four pivotal modules: the individualized model learning module, the risk-sensitive control module, the Bayesian optimization module, and the safety constraint module. Together, they establish a robust framework that employs advanced computational methodologies to deliver precise and personalized insulin dosage guidance, significantly improving the effectiveness and safety of diabetes treatment plans. The actual injection dose in the intervention group was executed by the doctor after approval based on the recommendation of the AP-A Dosage Decision Support System.	Device: AP-A Dosage Decision Support System; The AP-A Dosage Decision Support System represents a new solution in diabetes care, offering customized insulin dosage recommendations to patients. This system is a product of integrating four pivotal modules: the individualized model learning module, the risk-sensitive control module, the Bayesian optimization module, and the safety constraint module. Together, they establish a robust framework that employs advanced computational methodologies to deliver precise and personalized insulin dosage guidance, significantly improving the effectiveness and safety of diabetes treatment plans. The actual injection dose in the intervention group was executed by the doctor after approval based on the recommendation of the AP-A Dosage Decision Support System.
Active Comparator: Physician decision-making; The injection dose of the control group was determined by the doctor solely.	Device: AP-A Dosage Decision Support System; The AP-A Dosage Decision Support System represents a new solution in diabetes care, offering customized insulin dosage recommendations to patients. This system is a product of integrating four pivotal modules: the individualized model learning module, the risk-sensitive control module, the Bayesian optimization module, and the safety constraint module. Together, they establish a robust framework that employs advanced computational methodologies to deliver precise and personalized insulin dosage guidance, significantly improving the effectiveness and safety of diabetes treatment plans. The actual injection dose in the intervention group was executed by the doctor after approval based on the recommendation of the AP-A Dosage Decision Support System.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time in Range (TIR)	The proportion of time that the glucose levels, as recorded by CGM during the treatment period, are within the range of 3.9mmol/L to 10.0mmol/L. This metric can be directly obtained by the algorithm system through closed-loop reading of CGM data.	At the end of the treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time Below Range (TBR)	The proportion of time that the glucose levels, as recorded by CGM during the treatment adjustment period, are below 3.9mmol/L.	At the end of the treatment period
Other Secondary Outcomes1	The proportion of glucose data stored by CGM during the treatment period that is in the range of 3.0-3.8mmol/L.	At the end of the treatment period
Other Secondary Outcomes2	The proportion of glucose data stored by CGM during the treatment adjustment period that is below 3.0mmol/L.	At the end of the treatment period
Other Secondary Outcomes3	The area under the curve (AUC) of glucose levels below 3.9mmol/L in the Ambulatory Glucose Profile (AGP) during the treatment adjustment period.	At the end of the treatment period
Other Secondary Outcomes4	The proportion of glucose data stored by CGM during the treatment adjustment period that is above 10.0mmol/L.	At the end of the treatment period
Other Secondary Outcomes5	The proportion of glucose data stored by CGM during the treatment adjustment period that is above 13.3mmol/L.	At the end of the treatment period
Other Secondary Outcomes6	The area under the curve (AUC) of glucose levels below 10.0mmol/L in the AGP during the treatment adjustment period.	At the end of the treatment period
Other Secondary Outcomes7	The mean of the glucose data stored by CGM during the treatment adjustment period (MEAN).	At the end of the treatment period
Other Secondary Outcomes8	The standard deviation of the glucose data stored by CGM during the treatment adjustment period (SD).	At the end of the treatment period
Other Secondary Outcomes9	The discrepancy between the physician-approved dosage and the AI-recommended dosage in the intervention group.	At the end of the treatment period
Other Secondary Outcomes10	The number of times the physician-approved dosage differs from the AI-recommended dosage in the intervention group.	At the end of the treatment period
Other Secondary Outcomes11	In the intervention group, the proportion of time that the glucose levels are within the range of 3.9mmol/L to 10.0mmol/L within 4 hours after insulin injection when there is a discrepancy between the physician-approved dosage and the algorithm-recommended dosage.	At the end of the treatment period

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Collaborators: Xingtai People's Hospital; Hebei Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): March 30, 2025
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: May 13, 2024
• First Submitted That Met QC Criteria: May 13, 2024
• First Posted (Actual): May 17, 2024

Study Record Updates

• Last Update Posted (Actual): May 17, 2024
• Last Update Submitted That Met QC Criteria: May 13, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: 2023YFE0204100

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No