Feasibility Evaluation of an Artificial Pancreas With Glucose Prediction Trust Index

• ClinicalTrials.gov Identifier: NCT03092310
• Recruitment Status: Completed
• First Posted: March 27, 2017
• Last Update Posted: July 12, 2018
• Sponsor: Sansum Diabetes Research Institute
• Collaborator: Harvard University
• Information provided by (Responsible Party): Jordan Pinsker, Sansum Diabetes Research Institute

Study Description

Brief Summary:

The purpose of this pilot study is to establish that closed-loop insulin delivery with a target enchanted model predictive control (eMPC)/Health Monitoring System (HMS) algorithms with a trust index of the predicted glucose value is safe and effective, to analyze and learn to improve upon the accuracy of the predicted glucose values, and to collect efficacy data to inform a future larger study.

Condition or disease	Intervention/treatment	Phase
Type 1 Diabetes Mellitus	Device: Artificial Pancreas Device	Not Applicable

Detailed Description:

This is a feasibility study of an artificial pancreas (AP) system with our previously validated target eMPC and HMS algorithms, with the addition of a trust index of the predicted glucose value integrated into the portable Artificial Pancreas System (pAPS). The system will be evaluated on up to 20 subjects, with the goal of 10 subjects completing a 48-hour closed-loop session at one clinical site (William Sansum Diabetes Center). During the session subjects will bolus for all meals and snacks and perform a 45-minute walking session.

The purpose of this pilot study is to establish that closed-loop insulin delivery with a target enchanted model predictive control (eMPC)/Health Monitoring System (HMS) algorithms with a trust index of the predicted glucose value is safe and effective, to analyze and learn to improve upon the accuracy of the predicted glucose values, and to collect efficacy data to inform a future larger study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Feasibility Evaluation of an Artificial Pancreas With an Enhanced Model Predictive Control (eMPC) Controller and a Health Monitoring System (HMS) With a Glucose Prediction Trust Index
• Actual Study Start Date: March 20, 2017
• Actual Primary Completion Date: December 20, 2017
• Actual Study Completion Date: December 20, 2017

Arms and Interventions

Arm

Intervention/treatment

Experimental: Artificial Pancreas; The artificial pancreas device will employ its enhanced Model Predictive Control (MPC) algorithm with a target glucose level of 110 mg/dL with a trust index for MPC-predicted glucose values, weighing future glucose predictions and only acting on predictions with higher weight in the trust index. The Health Monitoring System algorithm uses the same CGM data as the MPC control algorithm but utilizes a separate algorithm for trending and predictions of future glucose values. Using a redundant and independent algorithm is an important safety feature of the overall AP device.

Device: Artificial Pancreas Device; Artificial Pancreas Device

Outcome Measures

Primary Outcome Measures :

1. Percent time within the target glucose range of 70-180 mg/dl overall as assessed by continuous glucose monitoring (CGM). [ Time Frame: 48 hours ]
   The primary endpoint for this pilot study will be time within the target glucose range of 70-180 mg/dl overall as assessed by continuous glucose monitoring (CGM), during closed-loop use, determining if the combination of eMPC and the assessment of trust index can provide safe and effective glucose control.

Secondary Outcome Measures :

1. Assessment of the trust index predictions vs. standard eMPC glucose predictions. [ Time Frame: 48 hours ]
   During closed-loop use, assessment of the trust index predictions vs. standard eMPC glucose predictions (frequency of moving away from nominal weights of predicted glucose).
2. Frequency of hypoglycemia during closed-loop use. [ Time Frame: 48 hours ]
   Frequency of hypoglycemia during closed-loop use, defined as percent time glucose is below predefined thresholds of 70 mg/dl, 60 mg/dl and 50 mg/dL.
3. Frequency of hyperglycemia during closed-loop use. [ Time Frame: 48 hours ]
   Frequency of hyperglycemia during closed-loop use, defined as percent time glucose is above predefined thresholds of 180 mg/dl, 250 mg/dl, and 300 mg/dL.
4. Percent time within the target glucose range of 70-140 mg/dl during closed-loop use. [ Time Frame: 48 hours ]
   Percent time within the target glucose range of 70-140 mg/dl overall as assessed by continuous glucose monitoring (CGM), during closed-loop use.
5. Percent time glucose is within range 70-150 mg/dl postprandial within 5 hours following meals, during closed-loop use. [ Time Frame: 48 hours ]
   Percent time glucose is within range 70-150 mg/dl postprandial within 5 hours following meals, during closed-loop use.
6. Standard Deviation and Coefficient of Variation of glucose values [ Time Frame: 48 hours ]
   To measure glycemic variability, the standard deviation and coefficient of variation of glucose values (as measured by continuous glucose monitoring) will be determined during the 48 hours of closed-loop use.
7. Markers of hypo- and hyperglycemia [ Time Frame: 48 hours ]
   Markers of hypo- and hyperglycemia, to include LBGI (Low blood glucose index) and HBGI (High blood glucose index), during closed-loop use.
8. Insulin Doses Given [ Time Frame: 48 hours ]
   Change in total daily doses and post prandial insulin doses given during the 48 hours of closed-loop use.
9. Number of treatments given for hypoglycemia (defined as carbohydrates given for treatment of a documented or suspected low blood sugar), during the 48 hours of closed-loop use. [ Time Frame: 48 hours ]
   Treatments for hypoglycemia given during the 48 hours of closed-loop use. Hypoglycemia treatments may be given in response to alerts from the HMS, if blood glucose < 70 mg/dL, or at the request of the subject or investigator.
10. Number of alerts given by the HMS to prevent hypoglycemia [ Time Frame: 48 hours ]
    Number of alerts given by the HMS to prevent hypoglycemia during closed-loop use.
11. Failure analysis of the devices/connectivity issues that may occur (# disconnects and device restarts). [ Time Frame: 48 hours ]
    Failure analysis of the devices/connectivity issues that may occur during closed-loop use. This includes number of CGM communication losses with 3 or more missed points, and number of times the entire system required a restart.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age ≥ 18 and ≤ 75 years at the time of screening.
• Clinical diagnosis of type 1 diabetes for at least one year.
• Has been using an insulin pump for at least 6 months at the time of screening.
• HbA1c < 10%, as performed by point of care or central laboratory testing. A1c will be assessed at the screening visit, or if already completed within 2 months of the screening visit, the prior lab value may be used in lieu of repeating this assessment.
• Serum creatinine of < 2.0 mg/dL. Serum creatinine will be assessed at the screening visit, or if already completed within 2 months of the screening visit, the prior lab value may be used in lieu of repeating this assessment.
• Bolus for all meals and snacks that contain ≥ 5 grams of carbohydrate.
• Willing to perform at least 7 fingerstick blood glucose tests a day.
• Willing to refrain from taking acetaminophen products for the duration of the clinical trial. If acetaminophen is taken, subject is to avoid making any insulin dosing decisions based on CGM for at least 12 hours.
• Willing to abide by the study protocol and use study-provided devices, including the Omnipod, Dexcom CGM, glucometer, ketone meter and pAPS tablet.

Exclusion Criteria:

• Pregnancy
• One or more episodes of hypoglycemia requiring an emergency room visit or hospitalization in the past 6 months.
• One or more episodes of hyperglycemia requiring an emergency room visit or hospitalization in the past 6 months.
• Known unstable cardiac disease or untreated cardiac disease, as revealed by history or physical examination.
• Dermatological conditions that would preclude wearing a CGM sensor or Pod.
• One or more seizures in the past year.
• Screening A1c ≥ 10% or serum creatinine ≥ 2.0 mg/dL.
• Any condition that could interfere with participating in the trial, based on investigator judgment.
• Concurrent use of any non-insulin glucose-lowering agent (including GLP-1 agonists, Symlin, DPP-4 inhibitors, SGLT-2 inhibitors, biguanides, sulfonylureas and naturaceuticals), defined as using any of these medications within 30 days of the screening visit or during the study.
• Participation in another pharmaceutical or device trial at the time of enrollment or during the study.

Contacts and Locations

Locations

United States, California

William Sansum Diabetes Center

Santa Barbara, California, United States, 93105

Sponsors and Collaborators

Sansum Diabetes Research Institute

Harvard University

Investigators

• Principal Investigator: Jordan E Pinsker, MD; Sansum Diabetes Research Institute
• Principal Investigator: Eyal Dassau, PhD; Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University
• Principal Investigator: Francis J Doyle III, PhD; Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University
• Principal Investigator: Alejandro Leguna, PhD; Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University

More Information

Publications of Results:

Pinsker JE, Laguna Sanz AJ, Lee JB, Church MM, Andre C, Lindsey LE, Doyle FJ 3rd, Dassau E. Evaluation of an Artificial Pancreas with Enhanced Model Predictive Control and a Glucose Prediction Trust Index with Unannounced Exercise. Diabetes Technol Ther. 2018 Jul;20(7):455-464. doi: 10.1089/dia.2018.0031.

• Responsible Party: Jordan Pinsker, Research Physician, Sansum Diabetes Research Institute
• ClinicalTrials.gov Identifier: NCT03092310 History of Changes
• Other Study ID Numbers: Pro00020556
• First Posted: March 27, 2017
• Last Update Posted: July 12, 2018
• Last Verified: July 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes
• Pediatric Postmarket Surveillance of a Device Product: No

Keywords provided by Jordan Pinsker, Sansum Diabetes Research Institute:

Artificial Pancreas

Additional relevant MeSH terms:

Diabetes Mellitus, Type 1; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Pancrelipase; Pancreatin; Gastrointestinal Agents