Feasibility of Closed-loop Automated Insulin Delivery System by Primary Care & Endocrinology, in Person & Via Telehealth

Study Overview
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Brief Summary
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This is a study assessing the feasibility of using the insulin-only configuration of the iLet bionic pancreas with initiation in pump-naïve people with type 1 diabetes in a primary care practice with either in-person training and follow-up (PC-IP) or with training and follow-up via telehealth (PC-TH). As a comparison, the iLet will be initiated by an academic endocrinology practice with either in-person training and follow-up (EN-IP) or with training and follow-up via telehealth (EN-TH).

Detailed Description
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This is a study assessing the feasibility of deploying the iLet bionic pancreas system in the insulin-only configuration to pump-naïve MDI users with type 1 diabetes, in the setting of being recruited from community-based primary care practices and being trained and managed by primary care providers (PC group), and in pump- and CGM-experienced (sensor-augmented pump or hybrid closed-loop) users with type 1 diabetes recruited from, trained, and managed by an academic endocrinology practice (EN group). In both practice settings, the exclusive use of telehealth (TH) visits will be assessed, as will the use of in-person (IP) visits. We will enroll 40 adult volunteers (≥ 18 years old) with type 1 diabetes, 20 who are insulin pump naïve MDI users enrolled from community primary care practices by University of Colorado Family Medicine (PC group) and 20 who are technology-savvy sensor-augmented pump or hybrid closed-loop users enrolled by the Massachusetts General Hospital Diabetes Clinical Research Center (EN group). Ten of the participants at each center will be trained and managed throughout the trial using in-person visits (PC-IP and EN-IP groups) and the other ten from each center will be trained and managed throughout the trial exclusively via telehealth visits (PC-TH and EN-TH groups). This will result in four study cohorts overall (endocrinology in-person, endocrinology telehealth, primary care in-person, primary care telehealth). Subjects in all four groups will each participate, in random order, in one 14-day study arm under their own usual care (UC arm) and one 14-day study arm under the insulin-only configuration of the iLet bionic pancreas (iLet arm).

Official Title
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Assessing Feasibility, Safety, and Efficacy of Deploying a Closed-loop Automated Insulin Delivery System by Community-based Primary Care Physicians and Academic Endocrinologists, in Person and Through Telehealth

Conditions
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Diabetes Mellitus, Type 1, Type 1 Diabetes, Diabetes, Autoimmune, Diabetes type1, Autoimmune Diabetes, Diabetes Mellitus, Brittle, Diabetes Mellitus, Insulin-Dependent, Diabetes Mellitus, Insulin-Dependent, 1, Diabetes Mellitus, Juvenile-Onset, Diabetes Mellitus, Ketosis-Prone, Diabetes Mellitus, Sudden-Onset, Insulin-Dependent Diabetes Mellitus 1, Juvenile-Onset Diabetes, Type 1 Diabetes Mellitus

Intervention / Treatment
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* Device: Bionic Pancreas
* Other: Telehealth
* Other: Usual Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Age 18-85 years, BMI ≥ 18.5, have had clinical type 1 diabetes for at least one year, and have taken insulin for at least 1 year Prescription diabetes medication regimen stable for > 1 month, including any adjunctive anti-diabetic medications (except for medications that will not affect the safety of the study and are not expected to affect any outcome of the study, in the judgment of the site principal investigator) This does not include changes to any insulin doses, including basal rates/long-acting insulin doses, carbohydrate to insulin ratios and correction factors Willing to wear one Dexcom CGM transmitter and sensor (sensor must be changed every 10 days), and one infusion set that must be replaced at least every 3 days. Endocrinology practice criterion is that diabetes is managed using sensor-augmented insulin pump therapy or artificial pancreas therapy for ≥ 3 months) Primary care practice criteria are that diabetes is managed by multiple daily insulin injections (insulin-pump naïve). TH group criterion is that participant must have hardware and internet access capable of 2-way video and audio communication Exclusion Criteria Unable to provide informed consent (e.g. impaired cognition or judgment) Unable to safely comply with study procedures and reporting requirements (e.g. impairment of vision or dexterity that prevents safe operation of the bionic pancreas, impaired memory) Unable to speak and read English, as iLet BP support materials and device menus are currently available in English only. Plan to change usual diabetes regimen in the next 3 months including before and during participation in the study This would include changing from MDI to pump or from pump to MDI, and starting a CGM if not previously used This would not include changes to any insulin doses, including basal rates/long acting insulin doses, carbohydrate to insulin ratios and correction factors Current use of non-FDA approved closed-loop or hybrid closed-loop insulin delivery system (e.g. Loop or Open APS) Unwilling to switch to lispro or aspart for the duration of the study's iLet arm (e.g. from Fiasp or Lyumjev) Known hemoglobinopathy (sickle cell trait is not an exclusion) Current participation in another diabetes-related clinical trial, has a medical condition, or use of a medication that, in the judgment of the investigator, could compromise the results of this study or the safety of the participant History of diabetes due to cystic fibrosis, pancreatitis, or other pancreatic disease, including pancreatic tumor or insulinoma, or history of complete pancreatectomy Have a history of intermittently required glucocorticoid treatment (e.g., but not limited to, for the treatment of asthma, inflammatory bowel disease). A1c >11.0% (most recent value up to 1 year prior acceptable; if none available or >1 year prior, participant will be instructed to obtain A1c through their usual care provider and to make copy of result available to study team) History of diabetic ketoacidosis (DKA) within the past month Electrically powered implants (e.g. cochlear implants, neurostimulators) that might be susceptible to RF interference Established history of allergy or severe reaction to adhesive or tape that must be used in the study Currently treated with GLP-1 analogue, thiazolidinedione (TZD), sulfonylurea, pramlintide, or SGLT-2 inhibitor medication (use more than 3 months prior to enrollment is acceptable) a. If using metformin, participants: i. Must be on a stable dose for 1 month prior to enrollment ii. Metformin can be continued while the iLet is used Pregnant (positive urine HCG), breast feeding, plan to become pregnant in the next 6 months, or premenopausal participants who are sexually active without use of contraception Renal failure on dialysis or chronic renal disease with a GFR or eGFR <30mL/min (values within the last two years will be accepted; if none available or >2 years prior, participant will be instructed to obtain GFR or eGFR through their usual care provider and to make copy of result available to study team) Any condition that, in the opinion of the site principal investigator, could interfere with the safe or effective completion of the study. a. Conditions to be considered by the investigator may include, but are not limited to, the following: i. Alcohol or drug abuse ii. Use of prescription drugs that may dull the sensorium, reduce sensitivity to symptoms of hypoglycemia, or hinder decision making during the period of participation in the study iii. Coronary artery disease that is not stable with medical management, including unstable angina, angina that prevents moderate exercise (e.g. exercise of intensity up to 6 METS) despite medical management, or within the last 12 months before screening, a history of myocardial infarction, percutaneous coronary intervention, enzymatic lysis of a presumed coronary occlusion, or coronary artery bypass grafting iv. Known history of prolonged QTc interval, malignant arrhythmia, or congenital heart disease v. Congestive heart failure with New York Heart Association (NYHA) Functional Classification III or IV vi. History of TIA or stroke in the last 12 months vii. Untreated or inadequately treated mental illness viii. History of eating disorder within the last 2 years, such as anorexia, bulimia, or diabulimia or omission of insulin to manipulate weight ix. History of intentional, inappropriate administration of insulin leading to severe hypoglycemia requiring treatment Employed by, or having immediate family members employed by Beta Bionics, or being directly involved in conducting the clinical trial, or having a direct supervisor at place of employment who is also directly involved in conducting the clinical trial (as a study investigator, coordinator, etc.); or having a first-degree relative who is directly involved in conducting the clinical trial Unable to avoid hydroxyurea for duration of study (interferes with accuracy of Dexcom G6 CGM)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Random-order cross over trial in a home-use setting with two 14-day study arms
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: EN-IP-UC<br>Random-order cross-over participants on USUAL CARE managed by ENDOCRINOLOGY with IN-PERSON visits. Participants will be randomly assigned to initiate trial participation with either Bionic Pancreas intervention or Usual Care intervention, followed by the other intervention. Each intervention will consist of 14 days. | Other: Usual Care<br>* 14 days of the participant's usual care of their type 1 diabetes<br>* Other names: UC;|
| Experimental: EN-TH-UC<br>Random-order cross-over participants on USUAL CARE managed by ENDOCRINOLOGY with TELEHEALTH visits. Participants will be randomly assigned to initiate trial participation with either Bionic Pancreas intervention or Usual Care intervention, followed by the other intervention. Each intervention will consist of 14 days. | Other: Telehealth<br>* Study participation will be managed via telehealth visits.<br>* Other names: TH;|
| Experimental: EN-IP-BP<br>Random-order cross-over participants on BIONIC PANCREAS managed by ENDOCRINOLOGY with IN PERSON visits. Participants will be randomly assigned to initiate trial participation with either Bionic Pancreas intervention or Usual Care intervention, followed by the other intervention. Each intervention will consist of 14 days. | Device: Bionic Pancreas<br>* 14 days using the insulin-only configuration of the iLet Bionic Pancreas (Beta Bionics, Inc.), which automates insulin delivery, as the only intended mode of insulin delivery.<br>* Other names: BP;|
| Experimental: EN-TH-BP<br>Random-order cross-over participants on BIONIC PANCREAS managed by ENDOCRINOLOGY with TELEHEALTH visits. Participants will be randomly assigned to initiate trial participation with either Bionic Pancreas intervention or Usual Care intervention, followed by the other intervention. Each intervention will consist of 14 days. | Device: Bionic Pancreas<br>* 14 days using the insulin-only configuration of the iLet Bionic Pancreas (Beta Bionics, Inc.), which automates insulin delivery, as the only intended mode of insulin delivery.<br>* Other names: BP;Other: Telehealth<br>* Study participation will be managed via telehealth visits.<br>* Other names: TH;|
| Active Comparator: PC-IP-UC<br>Random-order cross-over participants on USUAL CARE intervention managed by PRIMARY CARE with IN-PERSON visits. Participants will be randomly assigned to initiate trial participation with either Bionic Pancreas intervention or Usual Care intervention, followed by the other intervention. Each intervention will consist of 14 days. | Other: Usual Care<br>* 14 days of the participant's usual care of their type 1 diabetes<br>* Other names: UC;|
| Experimental: PC-TH-UC<br>Random-order cross-over participants on USUAL CARE managed by PRIMARY CARE with TELEHEALTH visits. Participants will be randomly assigned to initiate trial participation with either Bionic Pancreas intervention or Usual Care intervention, followed by the other intervention. Each intervention will consist of 14 days. | Other: Telehealth<br>* Study participation will be managed via telehealth visits.<br>* Other names: TH;|
| Experimental: PC-IP-BP<br>Random-order cross-over participants on BIONIC PANCREAS managed by PRIMARY CARE with IN PERSON visits. Participants will be randomly assigned to initiate trial participation with either Bionic Pancreas intervention or Usual Care intervention, followed by the other intervention. Each intervention will consist of 14 days. | Device: Bionic Pancreas<br>* 14 days using the insulin-only configuration of the iLet Bionic Pancreas (Beta Bionics, Inc.), which automates insulin delivery, as the only intended mode of insulin delivery.<br>* Other names: BP;|
| Experimental: PC-TH-BP<br>Random-order cross-over participants on BIONIC PANCREAS managed by PRIMARY CARE with TELEHEALTH visits. Participants will be randomly assigned to initiate trial participation with either Bionic Pancreas intervention or Usual Care intervention, followed by the other intervention. Each intervention will consist of 14 days. | Device: Bionic Pancreas<br>* 14 days using the insulin-only configuration of the iLet Bionic Pancreas (Beta Bionics, Inc.), which automates insulin delivery, as the only intended mode of insulin delivery.<br>* Other names: BP;Other: Telehealth<br>* Study participation will be managed via telehealth visits.<br>* Other names: TH;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of individuals with mean CGM glucose <183 mg/dL (corresponding to an estimated HbA1c of <8.0%) on days 3-14, by group. | The outcome is categorical, and the primary outcome is not a direct comparison of the mean CGM glucose between the groups. | BP Arm Days 3-14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean CGM glucose on days 3-14 |  | BP Arm Days 3-14 | 
| Percentage of time with CGM glucose <54 mg/dl on days 3-14 |  | BP Arm Days 3-14 | 
| Percentage of time with CGM glucose in the 70-180 mg/dl range on days 3-14 |  | BP Arm Days 3-14 | 
| Percentage of individuals with mean CGM glucose <154 mg/dL (corresponding to an estimated HbA1c of <7.0%) on days 3-14, by group. |  | BP Arm Days 3-14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bionic pancreas, closed loop, insulin, Pancreas, Artificial, automated insulin delivery system, t1d, t1dm