Hybrid Closed-Loop System in LADA Patients: A Randomized Trial

Application of a Hybrid Closed-Loop Artificial Pancreas System in Patients With Latent Autoimmune Diabetes in Adults (LADA): An Open-Label, Randomized Controlled Trial

Based on the difficulties in blood glucose control among the Latent Autoimmune Diabetes in Adults (LADA) population and the deficiencies of previous studies, this research aims to conduct a clinical comparative study. The short-term blood glucose control effects of the closed-loop system and the combination of a conventional insulin pump and Continuous Glucose Monitoring (CGM) in hospitalized LADA patients will be evaluated to explore the clinical application value of these methods in LADA patients. Moreover, this study aims to provide a more precise and personalized blood glucose management plan for LADA patients. As a slowly progressive subtype of autoimmune type 1 diabetes mellitus (T1DM), LADA patients have significant differences in pathological characteristics, clinical needs, and treatment effects compared with classical T1DM patients. However, they also face huge challenges in blood glucose management. This study will focus on LADA patients for the first time, especially the group of hospitalized patients, to fill the gap in this field. Meanwhile, by introducing the cutting-edge closed-loop system technology, it will provide new ideas and solutions for the clinical blood glucose management of LADA patients. Through a comparative analysis of the short-term blood glucose control effects of the closed-loop system and the combination of a conventional insulin pump and CGM, this study aims to provide more precise and personalized treatment strategies for LADA patients and promote the further development of diabetes treatment technologies.

Study Overview

• Status: Recruiting
• Conditions: Latent Autoimmune Diabetes in Adults (LADA)
• Intervention / Treatment: Other: Hybrid Closed-Loop Artificial Pancreas System

Detailed Description

This study aims to compare the clinical effects of a hybrid closed-loop artificial pancreas system and a traditional insulin pump in hospitalized patients with Latent Autoimmune Diabetes in Adults (LADA) through a single-center, open-label, randomized controlled trial. Referring to the designs of similar clinical trials, the number of cases in each group of this study is determined to be 25, with a total of 50 cases. The study subjects are LADA patients hospitalized in the Department of Endocrinology of Shanxi Bethune Hospital from April 2025 to April 2027. The study design is as follows: Starting from the second 24-hour period after the patient's admission, with each subsequent 24-hour period as a monitoring unit, after collecting baseline data, the patients are randomly divided into two groups: the closed-loop system group and the control group. The closed-loop system group uses a hybrid closed-loop artificial pancreas system combined with Continuous Glucose Monitoring (CGM), while the control group continues to use a traditional insulin pump combined with CGM. During the study, both groups wear CGM devices for continuous monitoring, and relevant clinical data are collected during and after the treatment for statistical analysis to compare the short-term blood glucose control effects of the two intensive insulin treatment regimens in hospitalized LADA patients.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Shiwei Liu, Doctor's degree; Phone Number: 0351-2170956 +86 13191072733; Email: lswspring6@aliyun.com

Study Locations

• China
  • Shanxi
    • Taiyuan, Shanxi, China, 030000
      • Recruiting
      • Shanxi Bethune Hospital
      • Contact: Li Chen, Master; Phone Number: 0351-8379146 13603530358; Email: chenli253@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age between 18 and 70 years old.

2. Meet the diagnostic criteria for LADA in the "Chinese Expert Consensus on the Diagnosis and Treatment of Latent Autoimmune Diabetes in Adults (2021 Edition)":

   • The onset age of diabetes is ≥ 18 years old.
   • Positive for islet autoantibodies or islet autoimmunity T cells.
   • Do not rely on insulin therapy for at least 6 months after the diagnosis of diabetes.
3. Patients are able to correctly use insulin pumps and CGM devices and have a certain learning ability and operational ability.
4. Baseline HbA1c > 7.0% or HbA1c > 6.0% combined with hypoglycemia.
5. Patients agree to participate in the study and sign the informed consent form.

Exclusion Criteria:

1. The patient has been clearly diagnosed with type 2 diabetes or special types of diabetes.
2. The patient has experienced acute diabetic complications within the past 1 month, such as diabetic ketoacidosis, hyperglycemic hyperosmolar coma, etc.
3. The patient has severe symptoms of hypoglycemia intolerance.
4. The patient has skin diseases such as rashes and prurigo, or abnormal coagulation function.
5. The patient has diseases related to impaired glucose metabolism, such as uncontrolled hyperthyroidism, hypothyroidism, Cushing's syndrome, etc.
6. The patient has comorbid severe liver, kidney, gastrointestinal, hematological, brain, circulatory system diseases, etc.
7. The patient has other severe chronic diseases (such as malignant tumors, end-stage organ failure, etc.).
8. The patient has impaired consciousness or mental illness, lacks self-control, and cannot express clearly.
9. Lactating women, pregnant women, or women who plan to become pregnant during the trial period.
10. The patient is currently using or has used glucocorticoids or other drugs that interfere with glucose metabolism within 1 month before screening.
11. The patient is allergic to the drugs involved in the clinical diagnosis and treatment plan.
12. The patient is currently using other closed-loop systems.
13. People who are not suitable for conventional insulin pump treatment and those with contraindications.
14. The patient is known or suspected to have an insulin-allergic constitution and is allergic to adhesive tape, insulin pumps, or CGM devices.

Other situations where the researcher deems the patient unfit to participate in the clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hybrid Closed-Loop Artificial Pancreas System with CGM Group; This group uses an open-source hybrid closed-loop artificial pancreas system with ultra-rapid-acting insulin (Novo Nordisk, Denmark). Daily insulin needs are calculated based on weight (0.3-0.6U/kg/day) & adjusted by the system. Physicians provide bolus instructions, entered by nurses. CGM & daily finger pricks are used for monitoring & calibration. The system predicts & prevents hypoglycemia, halting insulin when BG ≤ 4.4mmol/L. An alarm alerts for BG <3.9mmol/L.	Other: Hybrid Closed-Loop Artificial Pancreas System; Hybrid Closed-Loop Artificial Pancreas System Group: Uses an open-source system with Novo Nordisk ultra-rapid-acting insulin (approval: J20050097, 3 mL: 300 U). Daily insulin dose calculated at 0.3-0.6 U/(kg*d) based on weight; system auto-adjusts basal rate. Physicians prescribe bolus doses, entered by nurses via AAPS software. Glucose correction uses CGM + 4 daily capillary tests (fasting, 2h post-meal). AAPS features hypoglycemia prediction suspend (pauses basal if glucose ≤4.4 mmol/L, resumes upon recovery) and alarms (<3.9 mmol/L, ensures nighttime alert).
Placebo Comparator: Conventional Insulin Pump Combined with CGM Group; **According to the patient's weight, the total daily insulin requirement is calculated at a rate of 0.3 - 0.6 U/(kg·d) and distributed to pre-meal administrations based on the patient's specific condition. Blood glucose is monitored using a continuous glucose monitoring system in combination with daily fingerstick capillary blood glucose measurements (fasting blood glucose, and blood glucose 2 hours after breakfast, lunch, and dinner, for a total of 4 measurements). Insulin dosage is adjusted according to the patient's blood glucose levels until the blood glucose reaches the target level.**	Other: Hybrid Closed-Loop Artificial Pancreas System; Hybrid Closed-Loop Artificial Pancreas System Group: Uses an open-source system with Novo Nordisk ultra-rapid-acting insulin (approval: J20050097, 3 mL: 300 U). Daily insulin dose calculated at 0.3-0.6 U/(kg*d) based on weight; system auto-adjusts basal rate. Physicians prescribe bolus doses, entered by nurses via AAPS software. Glucose correction uses CGM + 4 daily capillary tests (fasting, 2h post-meal). AAPS features hypoglycemia prediction suspend (pauses basal if glucose ≤4.4 mmol/L, resumes upon recovery) and alarms (<3.9 mmol/L, ensures nighttime alert).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time required to achieve 70% TIR	Time in Range (TIR) refers to the percentage of time that blood glucose levels are within the target range of 3.9 to 10.0 mmol/L. The calculation formula is: TIR = (Time within the target range / Total time) × 100%	2 years
TIR achievement rate after 5 days of treatment	Time in Range (TIR) refers to the percentage of time that blood glucose levels are within the target range of 3.9 to 10.0 mmol/L. The calculation formula is: TIR = (Time within the target range / Total time) × 100%	5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Glucose Control Rate	The criteria for blood glucose target achievement are as follows: fasting blood glucose should be controlled within 4.0 - 7.0 mmol/L, postprandial blood glucose within 5.0 - 10.0 mmol/L, and blood glucose before going to bed within 4.4 - 7.8 mmol/L. The rate of blood glucose target achievement within 1 week of intensive insulin therapy will be statistically analyzed. The calculation formula is: Rate of blood glucose target achievement = (Number of patients achieving blood glucose targets / Total number of patients) × 100%	2 years
Time Below Range (TBR)、Time Above Range (TAR)	Time below the blood glucose target range, which is the percentage of time that blood glucose is below the target range of 3.9 mmol/L. The calculation formula is: TBR = (Time when blood glucose < 3.9 mmol/L in the target range / Total time) × 100%. Time above the blood glucose target range, which is the percentage of time that blood glucose is above the target range of 10.0 mmol/L. The calculation formula is: TAR = (Time when blood glucose > 10.0 mmol/L in the target range / Total time) × 100%.	2 years
Hypoglycemia Incidence Rate	The diagnostic criterion for hypoglycemia is a blood glucose level of 3.0 - 3.9 mmol/L. The hypoglycemia incidence rates during the treatment process in the two groups will be counted and compared. The diagnostic criterion for severe hypoglycemia is a blood glucose level < 3.0 mmol/L. The severe hypoglycemia incidence rates during the treatment process in the two groups will be counted and compared.	2 years
Inter-quartile Range (IQR) of Blood Glucose	The 25th and 75th percentile values of the blood glucose fluctuation range (inter - quartile range, IQR).	2 years
Average Daily Insulin Dosage	During the calculation period, record the specific dose of each injection every day.	2 years
Adverse Event	Count and compare the incidences of adverse events and serious adverse events during the treatment process between the two groups.	2 years

Collaborators and Investigators

• Sponsor: Shanxi Bethune Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: March 27, 2025
• First Submitted That Met QC Criteria: April 22, 2025
• First Posted (Actual): April 24, 2025

Study Record Updates

• Last Update Posted (Actual): April 24, 2025
• Last Update Submitted That Met QC Criteria: April 22, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Latent Autoimmune Diabetes in Adults; Diabetes Mellitus, Type 1; Gastrointestinal Agents; Pancrelipase
• Other Study ID Numbers: YXLL-2025-082

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: If there is a need to use data, please contact the person in charge and follow the relevant procedures to achieve data sharing. Without permission, do not use the data directly.

Drug and device information, study documents

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