Overnight MD-Logic

Study Overview
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Brief Summary
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Study design: Multicenter,randomized, prospective, open label, cross over, six segments, pilot trial to evaluate blood glucose control overnight under closed-loop insulin delivery with MD-Logic Artificial Pancreas (MDLAP) system in patients with type 1 diabetes. on the first segment 15 eligible subjects will be enrolled from the three participating centers (5 patients at each center). All 15 patients will participate in the overnight closed loop session in the hospital settings. On the second segment, 54 eligible subjects will be enrolled (18 at each center). Each subject will participate in the two consecutive overnight sessions in diabetes camp settings, one under closed-loop with MDLAP and one under sensor augmented pump therapy. In the third segment,9-20 eligible patients will be enrolled at the Israeli center only.Each subject will participate in up to four consecutive overnight under closed loop with MDLAP and up to four additional overnight under regular sensor augmented pump therapy at home. On the fourth segment, 45-60 patients will be enrolled at the Israeli center only. This segment will be conducted at a diabetes camp and will consist of two main parts. In part 1, 15-20 patients will be randomized to participate in one of the two groups: 2-4 nights under closed loop control while the MD-Logic learning algorithm is activated or 2-4 nights under closed loop control without activating the MD-Logic learning algorithm. In part 2 of the forth segment 30-40 patients will participate in two consecutive24-48 hours sessions,one under closed loop control and the second under sensor augmented pump therapy. On the fifth segment 40-80 eligible patients will be enrolled at the Israeli center only.The first 10 patients will participate in a pilot session and data gathered at this pilot session will not be used at the final analysis.This segment will consist of two parts. At part 1 each subject will participate in 4weeks-1.5 months period of over nights either using closed-loop with MDLAP or using sensor augmented pump (SAP) therapy.At the end of the first 4 weeks-1.5 months of the study, statistical analysis will be performed in order to decide whether to extend the study with an optional period of extra 4 weeks-1.5 months.In case it will be decided to extend the study, additional 4 weeks-1.5 months intervention period following completion of final visit activities will be offered to participants. Subjects that have participated in the control group (sensor augmented pump therapy) will be offered the opportunity to continue to 4 weeks-1.5 months of closed-loop control and the study group will be offered to switch to sensor augmented pump therapy. In segment 5 part 2, up to 40 patients will be enrolled. Each patient will participate in 3 months study period either using overnight closed loop under MDLAP or sensor augmented pump therapy.Participants in segment 5 part 2 will be offered to participate in part 2A. At this part, sleep quality assessment will be made (by using actigraf and sleep questionnaire) At the end of this period an optional 3 months extension period will be offered with the other arm (cross-over) Segment 6 will be consist of two main parts.In part 1, up to 40 eligible patients will be enrolled at the Israeli center only. Each subject will participate in up to 72 hours of closed-loop with MDLAP at home and up to 72 hours under regular sensor augmented pump therapy . The sequence of the treatment intervention will be randomly assigned. The sequence of the treatment intervention will be randomly assigned. In part 2 of this segment 40 eligible patients will enrolled at the Israeli center only. Each subject will participate in up to 2 weeks of closed loop with MDLAP at home and up to 2 weeks under regular sensor augmented pump therapy. The sequence of the treatment intervention will be randomly assigned Objectives: The objective of this feasibility study is to evaluate the safety and efficacy of blood glucose control using the MD-Logic Artificial Pancreas System in individuals with type 1 diabetes in the hospital settings,at a diabetes camp and finally at patient's home.

Detailed Description
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In the last two decades, remarkable technological progress has been made with the development of continuous glucose sensors, miniature devices, implantable pumps and sensors and wireless communications, interest in the closed-loop insulin delivery was revived. Control trails that evaluate the clinical benefits of continuous glucose sensor have shown improved HbA1c with no significant increase in sever hypoglycemia, trend towards lower hypoglycemic episodes although not significant and no significant change in sever hypoglycemia. One of the main drawbacks of continuous glucose sensor is noncompliant of the patient, the flow of information and the need to act accordingly makes this devise a burden for some patients. Theoretically subcutaneous insulin pumps and glucose sensors attached to an artificial pancreas in a closed-loop system can mimic the activity of functioning pancreatic beta cells, with strict control of blood glucose levels. Such a system may also offer an opportunity to free the patients from the daily burden of dealing with their diabetes. We developed the MD-Logic Artificial Pancreas (MDLAP) which is based on a model which imitates the logic of diabetes care givers. We aimed to evaluate blood glucose control overnight under closed- loop insulin delivery with MD-Logic Artificial Pancreas (MDLAP) system in patients with type 1 diabetes in the hospital settings,at diabetes camp settings and finally at patient's home . Study Objectives To determine the safety and efficacy of using the MDLAP system to automatically control blood glucose in type 1 diabetic patients. Study Scope This is a three center, prospective pilot trail to evaluate blood glucose control under closed-loop insulin delivery with MD-Logic Artificial Pancreas (MDLAP) system in patients with type 1 diabetes, being conducted in: Tel Aviv, Israel;Ljubljana, Slovenia and Hannover, Germany Study will be consist from six segments: In segment 1, 15 eligible patients will be enrolled for the pilot study. 5 patients will be recruited at each center.Data generated from the first patient at each center will not be included at the final statistical analysis and will be used to assess logistical and training issues only. On the second segment, 54 eligible subjects will be enrolled (18 at each center). Each subject will participate in the two consecutive overnight sessions in diabetes camp settings, one under closed-loop with MDLAP and one under sensor augmented pump therapy. Staying at a camp, can represent the home setting, but has on site the support of a medical team trained in diabetes. A remote safety and control diabetes management system will be utilized at this segment to enable the supervising personnel to alert the patient and intervene in cases of impending hypoglycemia, long standing hyperglycemia and technical faults of any component of the AP system. In the third segment,9-20 eligible patients will be enrolled at the Israeli center only.Each subject will participate in up to four consecutive overnight under closed loop with MDLAP and up to four additional overnight under regular sensor augmented pump therapy at home.In similar to segment 2, we will use also at segment 3 the remote safety and control diabetes management system which enable the supervising personnel to alert the patient or parents and intervene in cases of impending hypoglycemia, long standing hyperglycemia and technical faults of any component of the AP system. On the fourth segment, 45-60 patients will be enrolled at the Israeli center only, This segment will be conducted at a diabetes camp and will consist of two main parts. In part 1, 15-20 patients will be randomized to participate in one of the two groups: 2-4 nights under closed loop control while the MD-Logic learning algorithm is activated or 2-4 nights under closed loop control without activating the MD-Logic learning algorithm. In part 2 of the forth segment 30-40 patients will participate in two consecutive 24-48 hours sessions,one under closed loop control and the second under sensor augmented pump therapy. On the fifth segment 40-80 eligible patients will be enrolled at the Israeli center only and will be conducted at patient's home. This segment will consist of two main parts .The first 10 patients will participate in a pilot session and data gathered at this pilot session will not be used at the final analysis. At part 1 each subject will participate in 4 weeks-1.5 months period of over nights either using closed-loop with MDLAP or using sensor augmented pump (SAP) therapy.At the end of the first 4 weeks-1.5 months of the study, statistical analysis will be performed in order to decide whether to extend the study with an optional period of extra 4 weeks-1.5 months.In case it will be decided to extend the study, additional 4 weeks-1.5 months intervention period following completion of final visit activities will be offered to participants. Subjects that have participated in the control group (sensor augmented pump therapy) will be offered the opportunity to continue to 4 weeks-1.5 months of closed-loop control and the study group will be offered to switch to sensor augmented pump therapy. In segment 5 part 2, up to 40 patients will be enrolled. Each patient will participate in 3 months study period either using overnight closed loop under MDLAP or sensor augmented pump therapy. Participants in segment 5 part 2 will be offered to participate in part 2A. At this part, sleep quality assessment will be made (by using actigraf and sleep questionnaire). At the end of this period an optional 3 months extension period will be offered with the other arm (cross-over). Segment 6 will be consist of two main parts.In part 1 up to 40 eligible patients will be enrolled at the Israeli center only. Each subject will participate in up to 72 hours of closed-loop with MDLAP at home and up to 72 hours under regular sensor augmented pump therapy . The sequence of the treatment intervention will be randomly assigned. In part 2 of this segment 40 eligible patients will enrolled at the Israeli center only. Each subject will participate in up to 2 weeks of closed loop with MDLAP at home and up to 2 weeks under regular sensor augmented pump therapy. The sequence of the treatment intervention will be randomly assigned

Official Title
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Multicenter, Prospective, Open Label, Cross Over, Pilot Trial to Evaluate Blood Glucose Control Overnight Under Closed-loop Insulin Delivery With MD Logic Artificial Pancreas (MDLAP)System in Patients With Type 1 Diabetes

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Device: MD-logic Artificial Pancreas (MDLAP)
* Device: Standard treatment with insulin pump


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject with Type 1 diabetes (>1yr since diagnosis) Insulin infusion pump therapy for at least 3 months Patients whom uses continuous glucose sensor for at least 2 weeks(for segment 5) or will undergo run-in period of 2 weeks of glucose sensor wear before continue to baseline assessment (only for patients participating at segment 3 and 4) Age ≥ 10 years until 65 years HbA1c at inclusion ≥ 6.5 and <10 Patients willing to follow trail instructions Patients live with at least one other adult person (segment 3, 5, and 6 only) BMI Standard Deviation Score - below the 97th percentile for age(in segment 5 and 6 BMI SDS - below the 95th percentile for age) An internet connection at patient's home (only for patients participating at segment 3 and 6) Patients with care givers who are capable of operating a computer based system Exclusion Criteria: Concomitant diseases that influence metabolic control Participation in any other interventional study Known or suspected allergy to trial products Any significant diseases or conditions including psychiatric disorders and substance abuse that, in the opinion of the investigator, is likely to affect the subject's ability to complete the study, or compromise patient safety Diabetic ketoacidosis in the past 1 month. Severe hypoglycemia resulting in seizure or loss of consciousness in the month prior to enrollment. Current use of oral glucocorticoids or other medications, which in the judgment of the investigator would be a contraindication to participation in the study. Subject is participating in another drug or device study that could affect glucose measurements or glucose management.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 65 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: MD-logic Artificial Pancreas (MDLAP) system<br>Use of the closed loop MD-logic Artificial Pancreas(MDLAP)System | Device: MD-logic Artificial Pancreas (MDLAP)<br>* Treatment with the closed loop MD-logic Artificial Pancreas(MDLAP)System<br>|
| Active Comparator: Standard treatment with insulin pump<br>Standard treatment with sensor augmented pump therapy | Device: Standard treatment with insulin pump<br>* Standard treatment with sensor augmented pump therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of hypoglycemic events | Number of overnight hypoglycemic events below 63 mg/dl, between bed time to 07:00 | final visit (day 26 for participants at segment 1, day 14 for participants in segment 2 and 4 and day 20 for participants in segment 3) | 
| Time spent in hypoglycemia | Reduction of time spent in hypoglycemia defined as sensor glucose level below 60 mg/dL at segments 1&2 below 63 mg/dl at segment 3 and below 70 mg/dl in segment 5 | final visit (day 26 for participants at segment 1 , day 14 for participants in segment 2 and day 20 for participants in segment 3, 4 weeks-1.5 months for participants in segment 5) | 
| Reduction in overnight mean glucose level | Reduction in overnight mean glucose level | final visit (day 26 for participants at segment 1 and day 14 for participants in segment 2) | 
| Increase in time spent in the target range | Increase in time spent in the target range defined as sensor glucose level within 63 to 140 mg/dl (3.5 to 7.8 mmol/l) | day 14 for participants in segment 4 | 
| Increase in time spent in the target range of sensor glucose level within 70-180 mg/dl | Increase in time spent in the target range of sensor glucose level within 70-180 mg/dl | day 20 for participants in segment 4 part 2 and day 56 for participants in segment 6 | 
| Sleep efficacy | Sleep efficacy as measured by Actigraph | final visit (after7 months for participants at segment 5 part 2A) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of time spent in the target range | Percentage of time spent in the target range,defined as sensor glucose level within 63 to 140 mg/dl (3.5 to 7.8 mmol/l)and between 70 to 140 mg/dl(3.9 to 7.8 mmol/L) | final visit (day 26 for participants at segment 1 , day 14 for participants in segment 2 and 4 and day 20 for participants in segment 3) | 
| Percentage of time spent in the tight target range | Percentage of time spent in the target range, defined as sensor glucose level within 80 to 120 mg/dl (3.5 to 7.8 mmol/l) | final visit (day 26 for participants at segment 1, day 14 for participants in segment 2 and 4 and day 20 for participants in segment 3) | 
| Average (SD) of blood glucose levels | Average (SD) of blood glucose levels | final visit (day 26 for participants at segment 1and 4 and day 14 for participants in segment 2, day 20 for participants in segment 3, day 20 for participants in segment 4 part 2 and day 56 for participants in segment 6) | 
| Percentage of time spent below 60 mg/dl and below 70 mg/dl | Percentage of time spent below 60 mg/dl and below 70 mg/dl | final visit (day 26 for participants at segment 1, day 14 for participants in segment 2 and 4 and day 20 for participants in segment 3) | 
| Percentage of time spent above 140, 180, 250 mg/dl (7.8, 10, 13.9 mmol/l) | Percentage of time spent above 140, 180, 250 mg/dl (7.8, 10, 13.9 mmol/l) | final visit (day 26 for participants at segment 1, day 14 for participants in segment 2 and 4 and day 20 for participants in segment 3 ) | 
| Glucose variability | Glucose variability | final visit (day 26 for participants at segment 1, day 14 for participants in segment 2 and 4 and day 20 for participants in segment 3 ) | 
| Control Variability Grid Analysis (CVGA) | Control Variability Grid Analysis (CVGA) | final visit (day 26 for participants at segment 1 and day 14 for participants in segment 2) | 
| number of accurate alerts related to the remote safety and control diabetes management system | number of accurate alerts related to the remote safety and control diabetes management system | final visit (day 26 for participants at segment 1 and day 14 for participants in segment 2) | 
| Number of hypoglycemic events below 60 and 70 mg/dl (3.3, 3.9 mmol/l) | Number of hypoglycemic events below 60 and 70 mg/dl (3.3, 3.9 mmol/l) | final visit (day 26 for participants at segment 1, day 14 for participants in segment 2 and 4 and day 20 for participants in segment 3) | 
| Area under the curve <60,<63,<70,>140,>180,>250 mg/dl(3.3,3.5,3.9,7.8,10,13.9) | Area under the curve <60,<63,<70,>140,>180,>250 mg/dl(3.3,3.5,3.9,7.8,10,13.9) | final visit (day 26 for participants at segment 1, day 14 for participants in segment 2 and 4 and day 20 for participants in segment 3) | 
| • The percentage of nights mean overnight sensor glucose levels was within 90-140mg/dl (5-7.8 mmol/l) |  | final visit (day 14 ) for participants in segment 4 only | 
| Postprandial peak blood glucose and 2 hours postprandial blood glucose (segment 4 and 6 only) |  | Final visit (day 14 ) for participants in segment 4 part 1, day 20 for participants in segment 4 part 2 and day 56 for participants in segment 6 | 
| Artificial Pancreas technical performance, defined as the total frequency of failures | Artificial Pancreas technical performance, defined as The total frequency of failures (number of failures/night) of each following system components: sensor communication, pump communication, controller, user interface | Final visit (day 14 ) for participants in segment 4 only | 
| Analysis of the number of sensor data point not received to the artificial pancreas device divided by the total number of possible data points to be received. |  | Final visit (day 14 ) for participants in segment 4 only | 
| Percent time of active closed-loop control | Percent time of active closed-loop control defined as the number of minutes the MD-Logic system was functioning properly (computation of insulin infusion, and insulin actually delivered) divided by the maximum number of minutes the MD-Logic system should have been active (as per protocol) | Final visit (day 14) for participants in segment 4 only | 
| sensor accuracy | comparison of paired data points between capillary glucose level and Continuous Glucose Monitoring | final visit (day 14 for participants in segment 4 only) | 
| The time spent in hypoglycemia | The time spent in hypoglycemia below 50 mg/dl (2.8 mmol/l). | After 4 weeks-1.5 month at segment 5 only (in addition after additional 4 weeks-1.5 months if segment 5 will be extended) | 
| The number of hypoglycemic events below 60 and 50 mg/dl | The number of hypoglycemic events below 60 and 50 mg/dl (event defined duration of at least 20 minutes). | After 4 weeks- 1.5 months only at segment 5(in addition after additional 4 weeks-1.5 months if segment 5 will be extended) | 
| The time sensor glucose level spent within 70 to 140 mg/dl (3.9 to 7.8 mmol/l) |  | After 4 weeks- 1.5 months only at segment 5 (in addition after additional 4 weeks-1.5 months if segment 5 will be extended) | 
| The time spent in hyperglycemia | The time spent in hyperglycemia above 240 mg/dl (13.3 mmol/l). | After 4 weeks-1.5 monts only at segment 5 (in addition after additional 4 weeks-1.5 months if segment 5 will be extended) | 
| Patient's diabetes treatment satisfaction | Patient's diabetes treatment satisfaction using Diabetes Treatment Satisfaction Questionnaire | After 4 weeks-1.5 months only at segment 5 (in addition after additional 4 weeks-1.5 months if segment 5 will be extended) | 
| Acceptance and use intention of an Artificial Pancreas | Acceptance and use intention of an Artificial Pancreas for participant and for parents | after 4 weeks- 1.5 months only at segment 5(in addition after additional 4 weeks-1.5 months if segment 5 will be extended) | 
| Fear of hypoglycemia | Fear of hypoglycemia using questionaire | After 4 weeks- 1.5 months only at segment 5 (in addition after additional 4 weeks-1.5 months if segment 5 will be extended) | 
| Satisfaction with Artificial Pancreas | Satisfaction with Artificial Pancreas using questionaire | After 4 weeks- 1.5 months only at segment 5 (in addition after additional 4 weeks-1.5 months if segment 5 will be extended) | 
| Average percentage of overnight operation of the closed-loop control |  | After 4 weeks-1.5 months only at segment 5 (in addition after additional 4 weeks-1.5 months if segment 5 will be extended) | 
| Percentage of time spent below 50, 60, 70 mg/dl | Percentage of time spent below 50, 60, 70 mg/dl | day 20 for participants in segment 4 part 2 and day 56 for participants in segment 6 | 
| Number of hypoglycemic events below 50, 60, 70 mg/dl | Number of hypoglycemic events below 50, 60, 70 mg/dl | day 20 for participants in segment 4 part 2 and day 56 for participants in segment 6 | 
| Percentage of time spent above 180, 250 mg/dl | Percentage of time spent above 180, 250 mg/dl | day 20 for participants in segment 4 part 2 and day 56 for participants in segment 6 | 
| Number of readings below 70 mg/dl |  | day 20 for participants in segment 4 part 2 and day 56 for participants in segment 6 | 
| Automatic Caller System (ACS) technical performance and number of accurate alerts |  | final visit (after 7 months for participants at segment 5 part 2) | 
| number of research team intervention |  | final visit (after 7 months for participants at segment 5 part 2) | 
| HbA1c |  | final visit (after 7 months for participants at segment 5 part 2) | 
| Number of awake bouts per night | Number of awake bouts per night as measured by Actigraph | final visit (after 7 months for participants at segment 5 part 2A) | 
| Total wake up time per night | Total wake up time per night as measured by Actigraph | final visit (after 7 months for participants at segment 5 part 2A | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 diabetes, Closed loop, Artificial Pancreas