Efficacy and Safety of Android Artificial Pancreas System in Adult Patients With Type 1 Diabetes Mellitus in China

Study Overview
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Brief Summary
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This is a 26-week randomized, free-living, open-label, two-arm, two-phase, crossover trial. Participants will receive two interventions at different phases, including the Android artificial pancreas system(AndroidAPS-rt-CGM) and sensor-augment pump(SAP), and use marketed rapid-acting insulin analogs (insulin Aspart, insulin Lispro, or insulin Glulisine) normally used in their usual clinical care. The safety and efficacy of AndroidAPS-rt-CGM and SAP in adult T1DM with suboptimal glycemic control will be compared to explore whether the use of AndroidAPS-rt-CGM in adult T1DM with suboptimal glycemic control will be associated with better glycemic control with no increased hypoglycemia.

Detailed Description
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All participants will be free to live during the study. Each intervention phase is 12 weeks, preceded by a 2-week training period and separated by a 2-week washout period. During the training period, eligible participants will be trained to use the study rt-CGM and insulin pump and randomly assigned 1:1 to two treatment sequences after the training period. In Sequence A, patients use AndroidAPS-rt-CGM for the first intervention period (phase 1) and SAP for the second intervention period (phase 2); in Sequence B, patients use SAP for Phase 1 and AndroidAPS-rt-CGM for Phase 2. Participants who enter sequences A and B will be trained to use the study devices running in automated insulin delivery(AID) mode on the first day of phase 1 and phase 2, respectively. AndroidAPS-rt-CGM consists of three components:1) AiDEX G7 continuous glucose monitoring (an rt-CGM);2) Equil® insulin patch pump;3) AndroidAPS algorithm implemented in Android smartphone. The participants will use the study patch pump and rt-CGM, but the AndroidAPS algorithm and advanced features will not be allowed during the SAP intervention period. During the washout period, participants will continue using the study insulin pump with their standard settings, but the study rt-CGM will be replaced by daily self-monitoring of fingerstick glucose. The primary endpoint is time in range (3.9-10.0 mmol/L) derived from CGM. The main secondary endpoints include the percentage of sensor glucose values below, within, and above the target range; mean sensor glucose value; measures of glycemic variability, and centralized HbA1c. Safety endpoints mainly include the frequency of hypoglycemia events, diabetic ketoacidosis, and other serious adverse events.

Official Title
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Efficacy and Safety of Android Artificial Pancreas System Use at Home Among Type 1 Diabetes Mellitus Adults in China: Protocol of a 26-Week, Free-Living, Randomized, Open-Label, Two-Arm, Two-Phase, Crossover Trial

Conditions
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Diabetes Mellitus, Diabetes Mellitus, Type 1, Glucose Metabolism Disorders, Metabolic Disease, Endocrine System Diseases, Autoimmune Diseases, Immune System Diseases

Intervention / Treatment
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* Device: AndroidAPS-rt-CGM;
* Device: sensor augmented pump(SAP);


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prior to this study: Type 1 diabetes mellitus(T1DM) was diagnosed by an endocrinologist for at least one year. Aged from 18 to 75 years. HbA1c was 7.0%   11%. on multiple daily injection(MDI) or insulin pump therapy for ≥3 months with less than 20% insulin dose changes. The total daily dose(TDD) were≥0.3 u/kg /day, and the basal rate was ≥0.05 u/hour. Regular self-monitoring of blood glucose (≥3 times per day) for ≥2 months. Lived with an adult willing to care for the subject during the study. Women of childbearing age are willing to use appropriate contraceptive measures. Willing to follow the research protocol. Have daily access to a Wi-Fi network. Exclusion Criteria: Prior to this study: Severe acute or chronic complications of diabetes mellitus. Frequent severe hypoglycemia in the past three months. Patients who have used closed-loop therapy in the last two months (excluding those who have recently used CGM) and those participating in other studies. Abnormal liver function (ALT was 2.5 times higher than the upper limit of normal). Moderate to severe renal impairment (eGFR<60ml/min/1.73m2). Clinically significant heart disease. Pregnant or planning pregnancy. Used drugs that can interfere with glucose metabolism (e.g., exogenous glucocorticoids, nonselective beta-blockers, monoamine oxidase inhibitors) in the past eight weeks. Frequent acetaminophen, drug abuse, and excessive drinking. Known allergy to medical-grade adhesives or CGM and its affiliated components. Severe visual or hearing impairment. Severe skin disease at the site of sensor implantation. Plan to undergo elective surgery requiring general anesthesia during the study. Eating disorders such as anorexia or bulimia. Other physical or psychological conditions deemed inappropriate for inclusion by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AndroidAPS-rt-CGM<br>1) AiDEX G7 continuous glucose monitoring (an rt-CGM);2) Equil® insulin patch pump;3) AndroidAPS algorithm implemented in Android smartphone | Device: AndroidAPS-rt-CGM;<br>* Insulin therapy (aspart, lispro or glulisine) with AndroidAPS-rt-CGM.AndroidAPS-rt-CGM consists of three components:1) AiDEX G7 continuous glucose monitoring (an rt-CGM);2) Equil® insulin patch pump;3) AndroidAPS algorithm implemented in Android smartphone.<br>|
| Active Comparator: sensor augmented pump(SAP)<br>SAP includes only Equil® insulin patch pump and AiDEX G7 continuous glucose monitoring. | Device: sensor augmented pump(SAP);<br>* Insulin therapy (aspart, lispro or glulisine) with sensor augmented pump(SAP).SAP includes only Equil® insulin patch pump and AiDEX G7 continuous glucose monitoring.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time in range(TIR) | TIR(3.9-10.0 mmol/l) derived from CGM will be collected during the last 2 weeks of each phase. | during the last 2 weeks of each phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycosylated Hemoglobin A1c(HbA1c) | centralized HbA1c will be measured on the last day of each phase | on the last day of each phase | 
| Time in target range(TIT) | TIT(3.9-7.8 mmol/l) derived from CGM will be collected during the last 2 weeks of each phase. | during the last 2 weeks of each phase. | 
| Time above range(TAR) | TAR(> 10.0 mmol/L and > 13.9 mmol/L) derived from CGM will be collected during the last 2 weeks of each phase. | during the last 2 weeks of each phase. | 
| Time below range(TBR) | TBR(< 3.9 mmol/L and <3.0 mmol/L) derived from CGM will be collected during the last 2 weeks of each phase. | during the last 2 weeks of each phase. | 
| Mean blood glucose value(MBG) | MBG derived from CGM will be collected during the last 2 weeks of each phase. | during the last 2 weeks of each phase. | 
| Standard deviation(SD) | SD derived from CGM will be collected during the last 2 weeks of each phase. | during the last 2 weeks of each phase. | 
| Coefficient of variation(CV) | CV derived from CGM will be collected during the last 2 weeks of each phase. | during the last 2 weeks of each phase. | 
| Mean amplitude of glucose excursions(MAGE) | MAGE derived from CGM will be collected during the last 2 weeks of each phase. | during the last 2 weeks of each phase. | 
| the Chinese version of Hypoglycemia Fear Survey II-Worry Scale(HFS-II) | The Chinese version of Hypoglycemia Fear Survey II- Worry Scale is used to evaluate the psychological status of diabetic patients. Change in Hypoglycemia Fear Scale (HFS) score will be assessed in week 12 and week 26 adjusted for baseline(week 0 and week 14). These validated surveys include 18 questions to measure hypoglycemia-related anxiety and fear. Each item is rated on a 5-point Likert scale from 0(never related) to 4(very related). Never relative scores 1,  and very related scores 4. Patients with higher scores are considered with more anxiety and fear of hypoglycemia. The change in HFS-II will be assessed in week 12 and week 26 adjusted for baseline(weeks 0 and 14). | in week 0 ,week 12, week 14, and week 26 | 
| Frequency of hypoglycemia events | Level 1 is defined as sensor glucose ≤3.9mmol/L;level 2 is defined as sensor glucose ≤3.0mmol/L; level 3 is defined as hypoglycemia accompanied by severe cognitive impairment requiring the assistance of another individual to administer rescue therapy. | 12 weeks for each arm of the crossover | 
| Frequency of diabetic ketoacidosis (DKA) | DKA can be diagnosed when the following three points are met: 1)plasma glucose level ≥13.9mmol/L;2)pH<7.3 or bicarbonate <18 mmol/L;3)serum ketone ≥3mmol/L or urine ketone≥2+. | 12 weeks for each arm of the crossover | 
| Frequency of serious adverse events about device | Serious adverse device effect(ADE) is defined as an event related to the use of the study device which is fatal or life-threatening, resulting in persistent or substantial disability, or requires (or prolonged) hospitalization. | 12 weeks for each arm of the crossover | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adult, Type 1 diabetes mellitus;, Artificial pancreas system;, Do-it-yourself artificial pancreas system;, Automated insulin delivery;, Hybrid closed loop;, AndroidAPS