The Insulin-Only Bionic Pancreas Pivotal Trial: Testing the iLet in Adults and Children With Type 1 Diabetes
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 440
- 试验地点
- 31
- 主要终点
- HbA1c
研究概览
简要总结
This multi-center randomized control trial (RCT) will compare efficacy and safety endpoints using the insulin-only configuration of the iLet Bionic Pancreas (BP) System versus Usual Care (UC) during a 13-week study period. Participants may be enrolled initially into a screening protocol and then transfer into the RCT protocol, or they may enter directly into the RCT protocol. The RCT will be followed by an Extension Phase in which the RCT Usual Care (UC) Group will use the insulin-only configuration of the iLet Bionic Pancreas (BP) System for 3 months. At the completion of use of the BP system in the RCT only, participants will enter a 2-4 day Transition Phase and be randomly assigned to either transition back to their usual mode of therapy (MDI or pump therapy) based on therapeutic guidance from the iLet BP System or transition back to their usual mode of therapy based on what their own insulin regimens were prior to enrolling in the RCT.
There is an optional ancillary study to assess the safety of utilizing self-monitored blood glucose (SMBG) measurements instead of continuous glucose monitor (CGM) measurements as input into the iLet for ~48-60 hours. The Study is intended to mirror a real-world situation where CGM may not be available for an extended period of time (eg, user runs out of sensors and is awaiting new shipment).
详细描述
Primary Objective
• To compare the efficacy and safety of the insulin-only configuration of the iLet BP System (using insulin lispro, insulin aspart) the BP System using Fiasp (BPFiasp) [adults only]) in maintaining near-normal glycemia relative to usual care in a home-use study in adults and children with T1D.
Secondary Objectives • To assess the impact of the insulin-only configuration of the iLet BP System on quality of life and treatment satisfaction.
The study has four major parts: (1) the Test-Run Phase, (2) the RCT Period, (3) the Extension Phase for the UC Arm, and (4) the Transition Phase. These four parts are described below, and detailed in the main part of the protocol.
A Test-Run Phase will be conducted to (1) test the functionality of all aspects of the iLet BP System, (2) train the clinical staff on the execution of the clinical protocol, and (3) provide hands-on training with the device prior to initiating the RCT Period. The initial test run will be conducted at one site (MGH) with ~5 participants using the iLet BP system for 4-7 days. If there are no safety or consequential device issues, a test run will be conducted at each of the other 15 sites, with ~2 participants per site using the iLet BP system for 4-7 days. The iLet BP system will use insulin lispro or insulin aspart. Results of this Test-Run Phase will be evaluated for safety prior to beginning the RCT Period as described in section 3.3.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of T1D for at least one year and using insulin for at least 1 year
- •Diabetes managed using the same regimen (either pump or MDI, with or without CGM) for ≥ 3 months
- •Age ≥ 6 years old
- •Exception: the initial 5-participant test run will be limited to >18 years old
- •Current use of a CGM, or if not a CGM user, at least 3 blood glucose meter tests daily on average over the last 4 weeks (according to judgment of investigator if meter is not available).
- •Willingness not to start any new non-insulin glucose-lowering agent during the course of the trial
- •For participants <18 years old, living with one or more parent/legal guardian knowledgeable about emergency procedures for severe hypoglycemia.
- •For participants >18 years old who live alone, participant has a relative or acquaintance who lives within 30 minutes of participant and is willing to be contacted to check on participant if study staff feel that participant may be experiencing a medical emergency and can't be reached.
- •Investigator believes that the participant can safely use the iLet and will follow the protocol
- •The investigator will take into account the participant's HbA1c level, compliance with current diabetes management, and prior acute diabetic complications. For this reason, there is no upper limit on HbA1c specified for eligibility.
- •If a GLP-1 agonist or pramlintide is being used, participant must be willing to discontinue use while the iLet BP system is being used, including the randomized trial and extension study.
排除标准
- •Eligibility may be assessed initially in a separate screening protocol or at a screening visit in the RCT protocol. To be eligible for all phases of the study, a participant must meet all of the following inclusion criteria and none of the 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
- •For pediatric participants, both caregivers and participants must be able to speak and read English
- •Plan to change usual diabetes regimen in the next 3 months
- •This would include changing from MDI to pump. pump to MDI, change in insulin automation delivery system, starting a CGM if not previously used, changes in drug therapy specifically for glucose control except for changes in one insulin analog to another.
- •Changes in insulin dose, carb ratio, sensitivity factor and basal rate profile are allowed.
- •Current use of non-FDA approved closed-loop or hybrid closed-loop insulin delivery system
- •Use of Apidra as the pre-study rapid-acting insulin analog and unwilling to switch to lispro or aspart for the duration of the study
- •Known hemoglobinopathy (sickle cell trait is not an exclusion)
- •Current participation in another diabetes-related clinical trial
- •History of cystic fibrosis, pancreatitis, or other pancreatic disease, including pancreatic tumor or insulinoma, or history of complete pancreatectomy
- •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
- •Current use of SGLT2 inhibitors or a sulfonylurea drug (use more than 3 months prior to enrollment is acceptable)
- •If using GLP1 agonist, pramlintide, or metformin drugs must be on a stable dose for 3 months prior to enrollment (and as per inclusion criterion #8, must be willing to discontinue use of GLP-1 agonist or pramlintide while using the iLet BP system during the RCT and the extension phase).
- •Pregnant (positive urine hCG), breast feeding, plan to become pregnant in the next 3 months, or sexually active without use of contraception
- •For adults >18 years old, most recent (must be within the last 2 years) eGFR <30 ml/min OR currently in renal failure on dialysis
- •If no eGFR is available for an adult participant during the last 2 years, one must be obtained to confirm eligibility
- •Presence of a medical condition or use of a medication that, in the judgment of the investigator, clinical protocol chair, or medical monitor, could compromise the results of the study or the safety of the participant. Conditions to be considered by the investigator may include the following:
- •Alcohol or drug abuse
- •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
- •Coronary artery disease that is not stable with medical management, including unstable angina, angina that prevents moderate exercise (e.g. climbing a flight of stairs) 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
- •Congestive heart failure with New York Heart Association (NYHA) Functional Classification III or IV
- •History of TIA or stroke in the last 12 months
- •Untreated or inadequately treated mental illness
- •History of eating disorder within the last 2 years, such as anorexia, bulimia, or diabulemia or omission of insulin to manipulate weight
- •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
结局指标
主要结局
HbA1c
时间窗: 13 weeks
The primary outcome is superiority for central lab hemoglobin A1c at 13 weeks. Glycated Hemoglobin A1C (HbA1c) is a physiological marker of the percentage of red blood cells that have glycated (bonded with a sugar). HbA1c is used to measure changes in average blood sugar over the past three months.
次要结局
- CGM-Measured Glucose Coefficient of Variation Over 13 Weeks(13 weeks)
- CGM-measured Percentage Time <54 mg/dL Over 13 Weeks(13 weeks)
- Other Secondary Efficacy Endpoint: HbA1c <7.0% in Participants With Baseline HbA1c >7.5%(13 weeks)
- Other Secondary Efficacy Endpoint: CGM-measured Percentage Time <60 mg/dL Over 13 Weeks(13 weeks)
- Non-inferiority for CGM-measured Time <54 mg/dL (Key Secondary Endpoint)(13 weeks)
- CGM-measured Percentage Time 70-180 mg/dL Over 13 Weeks(13 weeks)
- Other Secondary Efficacy Endpoint: HbA1c <7.0%(13 weeks)
- Other Secondary Efficacy Endpoint: HbA1c <7.5%(13 weeks)
- Other Secondary Efficacy Endpoint: HbA1c <8.0%(13 weeks)
- Other Secondary Efficacy Endpoint: CGM-measured Percentage Time in Range 70-140 mg/dL Over 13 Weeks(13 weeks)
- Other Secondary Efficacy Endpoint: CGM-measured Percentage Time in Range 70-120 mg/dL Over 13 Weeks(13 weeks)
- CGM-measured Mean Glucose Level Over 13 Weeks(13 weeks)
- CGM-measured Percentage Time >180 mg/dL Over 13 Weeks(13 weeks)
- CGM-measured Glucose Standard Deviation (SD) mg/dL Over 13 Weeks(13 weeks)
- CGM-Measured Percentage Time <70 mg/dL Over 13 Weeks(13 weeks)
- Other Secondary Efficacy Endpoint: HbA1c Relative Improvement >10%(13 weeks)
- Other Secondary Efficacy Endpoint: HbA1c Improvement >1.0% or HbA1c <7.0% at 13 Weeks(13 weeks)
- Other Secondary Efficacy Endpoint: CGM-measured Percentage Time <70 mg/dL <4%(13 weeks)
- Other Secondary Efficacy Endpoint: Improvement in HbA1c > 0.5% Without an Increase in Time < 54 mg/dl by > 0.5% OR Improvement in Time < 54 mg/dl by > 0.5% Without an Increase in HbA1c by > 0.5%(13 weeks)
- CGM-measured Percentage Time >250 mg/dL Over 13 Weeks(13 weeks)
- Other Secondary Efficacy Endpoint: HbA1c Improvement >1.0%(13 weeks)
- Other Secondary Efficacy Endpoint: CGM-measured Area Under the Curve 180 mg/dL Over 13 Weeks(13 weeks)
- Other Secondary Efficacy Endpoint: CGM-measured Percentage Time in Range 70-180 mg/dL >70% Over 13 Weeks(13 weeks)
- Other Secondary Efficacy Endpoint: Time in Range 70-180 mg/dL Improvement From Baseline to 13 Weeks ≥10%(13 weeks)
- Other Secondary Efficacy Endpoint: Body Mass Index (BMI) at Week 13(13 weeks)
- Other Secondary Efficacy Endpoint: Mean Participant-reported Grams of Carbohydrate Taken Specifically to Prevent or Treat Hypoglycemic Events Per 24 Hours(13 weeks)
- Other Secondary Efficacy Endpoint: HbA1c >9.0%(13 weeks)
- Other Secondary Efficacy Endpoint: HbA1c Improvement >0.5%(13 weeks)
- Other Secondary Efficacy Endpoint: CGM-measured Hyperglycemic Events(13 weeks)
- Other Secondary Efficacy Endpoint: Mean of Daily Difference in Mean Glucose(13 weeks)
- Other Secondary Efficacy Endpoint: Time in Range 70-180 mg/dL Improvement From Baseline to 13 Weeks ≥5%(13 weeks)
- Other Secondary Efficacy Endpoint: Mean Glucose <154 mg/dL and Time <54 mg/dL <1%(13 weeks)
- Other Secondary Efficacy Endpoint: Total Daily Insulin (Units/kg)(13 weeks)
- Other Secondary Efficacy Endpoint: Improvement in Time 70-180 mg/dl by >10% Without an Increase in Time < 54 mg/dl by > 0.5% OR Improvement in Time < 54 mg/dl by > 0.5% Without a Decrease in Time 70-180 mg/dl by > 10%(13 weeks)
- Other Secondary Efficacy Endpoint: CGM-measured Area Over the Curve 70 mg/dL Over 13 Weeks(13 weeks)
- Other Secondary Efficacy Endpoint: High Blood Glucose Index (HBGI)(13 weeks)
- Other Secondary Efficacy Endpoint: Blood Glucose Risk Index (LBGI + HBGI)(13 weeks)
- Other Secondary Efficacy Endpoint: Percentage Change in the TDD of Insulin Over the First Two-week Period Relative to the TDD of Insulin in the Last Two-week Period(Weeks 1-2 and weeks 12-13)
- Other Secondary Efficacy Endpoint: Body Weight at Week 13(13 weeks)
- Other Secondary Efficacy Endpoint: Low Blood Glucose Index (LBGI)(13 weeks)
- Other Secondary Efficacy Endpoint: CGM-measured Hypoglycemic Events(13 weeks)
- Other Secondary Efficacy Endpoint: CGM-measured Percentage Time >300 mg/dL Over 13 Weeks(13 weeks)
- Other Secondary Efficacy Endpoint: CGM-measured Percentage Time <54 mg/dL <1%(13 weeks)
- Other Secondary Efficacy Endpoint: Time in Range 70-180 mg/dL >70% and Time <54 mg/dL <1%(13 weeks)
- Other Secondary Efficacy Endpoint: Mean Participant-reported Number of Hypoglycemic Events Requiring Carbohydrate Treatment Per 24 Hours(13 weeks)