Pilot Study of Closed-Loop Glucose Control in People With Type 1 Diabetes (BPK004)

Not Applicable

Completed

Conditions: Type 1 Diabetes

Interventions: Device: Closed-Loop, Model Predictive Control (MPC)
Device: Open-Loop

Registration Number: NCT00977808

Lead Sponsor: University of Virginia

Brief Summary: This study plans to link two existing technologies, the insulin pump and the continuous glucose monitor (CGM), to essentially develop an artificial pancreas, i.e., closed-loop. This will be done using two continuous glucose monitors (CGMs), a computer containing an investigational control algorithm that uses glucose information from the CGM to recommend insulin dosing, and an insulin pump. The purpose of this study is to test the ability of continuous glucose monitors together with an insulin pump and a mathematical formula to control blood sugar levels of people with type 1 diabetes.

The Closed-Loop control algorithm will:

1. Suggest adequate insulin delivery for blood glucose control in steady state (overnight);

2. Cover adequately with an insulin bolus the pre-set carbohydrate content of a breakfast.

If successful, this study will conceptually prove the feasibility of automated model-predictive closed-loop glucose control in T1DM.

Detailed Description: Each patient had an outpatient screening evaluation, and two 22 h overnight hospital admissions separated by a 2- to 4-week waiting period. Each inpatient admission began at 15:00 and ended at 13:00 on the following day. Subjects ate dinners and lunches with carbohydrate content that was the same at admission 1 and admission 2 and had identical morning meals of Ensure Plus (Abbott Nutrition, Columbus, OH). Two days before each admission, two Freestyle Navigator CGM devices (Abbott Diabetes Care) continuous glucose monitors were applied to the patient to allow for stabilization of the sensors and for assessment of their performance.

During admission 1, open-loop control was used, with the subjects' usual insulin routine and their personal insulin pump. During admission 2, an OmniPod Insulin Management System (Insulet Corp.) was inserted and used for closed-loop control of blood glucose. Insulin lispro (Eli Lilly, Indianapolis, IN), chosen based on commercial assays available, was used during both inpatient admissions.

At the beginning of admission 2, one of the two CGM devices was designated as primary, and the closed-loop control algorithm used the data of that system, unless a problem was detected. At 17:00, the model-predictive control (MPC) was initiated in a data-collection mode, automatically receiving CGM data every minute. Administration of the predinner insulin bolus was overseen by the attending physician. MPC, closed-loop control began at 21:30 and continued until 12:00 the next day for a total of 14.5 h.

Per FDA restrictions, the algorithm did not automatically control the insulin pump. Instead, the algorithm suggested insulin boluses every 15 min, which, if accepted, were programmed into the insulin pump by the attending physician. This was done for safety reasons, allowing the physician to override insulin delivery suggestions at any time. Reference blood glucose (using a YSI Life Sciences or a Beckman glucose analyzer) was sampled every 30 min. The protocol required switching to more frequent 15 min reference blood glucose sampling if hypoglycemia occurred or was imminent. Fast-acting carbohydrate (glucose tablets or fruit juice) was given when reference blood glucose fell below 3.9 mmol/liter, regardless of the CGM readings.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 12

Inclusion Criteria

21 years of age or older
Have Type 1 Diabetes Mellitus as defined by American Diabetes Association criteria or judgment of physician for at least 2 years (including those who may also be treated with metformin, thiazolidinedione, exenatide, or pramlintide).
Use of an insulin pump
If on antihypertensive, thyroid, anti-depressant or lipid lowering medication, have stability on the medication for at least 1 month prior to enrollment in the study
Willingness to use lispro (Humalog) insulin for the duration of the inpatient study
Demonstration of proper mental status and cognition for the study

Exclusion Criteria

Age <21
Pregnancy
Hematocrit <36% (females); <38% (males)
Symptomatic coronary artery disease (e.g. history of myocardial infarction, history of acute coronary syndrome, history of therapeutic coronary intervention, history of coronary bypass or stenting procedure, stable or unstable angina, episode of chest pain of cardiac etiology with documented EKG changes, positive stress test or catheterization with coronary blockages >50%).
Congestive heart failure
History of a cerebrovascular event
Use of a medication that significantly impacts glucose metabolism (oral steroids)
Atrial fibrillation
Uncontrolled hypertension (resting blood pressure >140/90)
History of a systemic or deep tissue infection with methicillin-resistant staph aureus or Candida albicans
Use of a device that may pose electromagnetic compatibility issues and/or radiofrequency interference with the FreeStyle NavigatorTM CGM (implantable cardioverter-defibrillator, electronic pacemaker, neurostimulator, intrathecal pump, and cochlear implants)
Active enrollment in another clinical trial
Allergy or adverse reaction to lispro insulin
Known adrenal gland problem, pancreatic tumor, or insulinoma
Current alcohol abuse, substance abuse, or severe mental illness
Retinopathy and renal failure
Uncontrolled anxiety or panic disorder
Known bleeding diathesis or dyscrasia
Renal insufficiency (creatinine >1.5)
Any comorbid condition affecting glucose metabolism

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Closed-Loop Model Predictive Control (MPC)	Closed-Loop, Model Predictive Control (MPC)	Insulin dosing was performed by a model-predictive control (MPC) algorithm.
Open-Loop	Open-Loop	Insulin dosing was performed by the patient (using their normal routine and personal insulin pump) under a physician's supervision.

Primary Outcome Measures

Name	Time	Method
Occurrence of Hypoglycemic Episodes	Overnight (21:30 until 08:00)	Hypoglycemic events were defined as below 3.9 mmol/liter and the percentage of time within the range of 3.9 to 7.8 mmol/liter overnight (21:30 until 08:00) as measured by reference blood glucose (YSI or Beckman Glucose Analyzer).

Secondary Outcome Measures