Effect of Gain on Closed-Loop Insulin

Joslin Diabetes Center

Status: Completed

Conditions: Type 1 Diabetes

Treatments: Device: LOW error; Device: HIGH error; Device: NO error

Study type: Interventional

Funder types: Other

Identifiers

NCT02065895

2012P-000401

Details and patient eligibility

About

The purpose of this study is to test the ability of an advanced external Physiologic Insulin Delivery (ePID) algorithm (a step by step process used to develop a solution to a problem) to get acceptable meal responses over a range of gain. Gain is defined as how much insulin is given in response to a change in a patient's glucose level.

This study also examines the effectiveness of the external Physiologic Insulin Delivery (ePID) closed-loop insulin delivery computer software. The investigators would like to assess whether fasting target levels can be achieved as the closed-loop gain increases or decreases, and to evaluate the system's ability to produce an acceptable breakfast meal response.

Full description

There have been significant advances in diabetes management technology, including more sophisticated insulin pumps and more accurate real-time continuous glucose monitors. The next technological development is widely thought to be the introduction of an algorithm linking the pump and sensor to form a closed-loop insulin delivery system. The algorithm used for this purpose needs to be robust to changes in an individual's insulin sensitivity, and the sensor's sensitivity to glucose. Insulin sensitivity (how much the patient's glucose level changes in response to a change in insulin delivery) and algorithm gain (how much insulin is delivered in response to a change in glucose) determine the systems overall closed-loop gain. Ideally, the overall gain can be set to achieve the lowest possible peak postprandial glucose response without postprandial hypoglycemia. However, if the algorithm's gain is set to a fixed value and the subject's insulin sensitivity changes, the overall-gain will change. Some degradation in closed-loop performance might be acceptable during periods whenever the subject's insulin sensitivity is low (i.e., the subject is insulin resistant) and the risk of hypoglycemia may actually be reduced. However, if the subject becomes more sensitive the system may become less stable and the risk of postprandial hypoglycemia may increase. In addition to changes in insulin sensitivity, glucose sensors will sometimes over- or under-read blood glucose as sensor sensitivity increases or decreases. This will result in a change in the closed-loop algorithm's effective target. The purpose of this study is to evaluate the ability of an advanced Physiologic Insulin Delivery algorithm to achieve an acceptable breakfast response as the gain and effective target glucose level changes. Specifically:

1. to assess the fasting glucose levels achieved as the overall closed-loop gain and effective target is increased or decreased, and
2. determine the system's ability to produce an acceptable breakfast meal response under these conditions

Enrollment: 8 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Type 1 diabetes for > 3 years
• Manage diabetes using a continuous glucose monitor and continuous subcutaneous insulin infusion pump
• Non obese (BMI < 30)
• Aged 18 - 75 years old
• HbA1c < 8 %

Exclusion criteria

• renal or hepatic failure
• cancer or lymphoma
• Malabsorption or malnourishment
• Hypercortisolism
• Alcoholism or drug abuse
• Anemia (hematocrit < 36 in females and <40 in males)
• Eating disorder
• Dietary restrictions
• Acetaminophen allergy
• Chronic acetaminophen use
• Glucocorticoid therapy
• History of gastroparesis
• Use of Beta blockers

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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8 participants in 6 patient groups

HIGH error, LOW error, NO error

Experimental group

Description:

Subjects were randomized to receive overnight and breakfast closed-loop glucose control glucose on three occasions: first with glucose-value-used-for-control higher than blood glucose (HIGH error), then second with glucose-value-used-for-control lower than blood glucose (LOW error), then third with glucose-value-used-for-control equal blood glucose (NO error).

Treatment:

Device: NO error

Device: HIGH error

Device: LOW error

HIGH error, NO error, LOW error

Experimental group

Description:

Subjects were randomized to receive overnight and breakfast closed-loop glucose control glucose on three occasions: first with glucose-value-used-for-control higher than blood glucose (HIGH error), then second with glucose-value-used-for-control equal blood glucose (NO error), then third with glucose-value-used-for-control lower than blood glucose (LOW error).

Treatment:

Device: NO error

Device: HIGH error

Device: LOW error

NO error, HIGH error, LOW error

Experimental group

Description:

Subjects were randomized to receive overnight and breakfast closed-loop glucose control glucose on three occasions: first with glucose-value-used-for-control equal blood glucose (NO error), then second with glucose-values-used-for-control higher than blood glucose (HIGH error), then third with glucose-value-used-for-control lower than blood glucose (LOW error).

Treatment:

Device: NO error

Device: HIGH error

Device: LOW error

NO error, LOW error, HIGH error

Experimental group

Description:

Subjects were randomized to receive overnight and breakfast closed-loop glucose control glucose on three occasions: first with glucose-value-used-for-control equal blood glucose (NO error), then second with glucose-value-used-for-control lower than blood glucose (LOW error), then third with glucose-value-used-for-control higher than blood glucose (HIGH error).

Treatment:

Device: NO error

Device: HIGH error

Device: LOW error

LOW error, NO error, HIGH error

Experimental group

Description:

Subjects were randomized to receive overnight and breakfast closed-loop glucose control glucose on three occasions: first with with glucose-value-used-for-control lower than blood glucose (LOW error), then second with glucose-value-used-for-control equal blood glucose (NO error), then third with glucose-value-used-for-control higher than blood glucose (HIGH error).

Treatment:

Device: NO error

Device: HIGH error

Device: LOW error

LOW error, HIGH error, NO error

Experimental group

Description:

Subjects were randomized to receive overnight and breakfast closed-loop glucose control glucose on three occasions: first with glucose-value-used-for-control lower than blood glucose (LOW error), then second with glucose-value-used-for-control equal blood glucose (NO error), then third glucose-value-used-for-control higher than blood glucose (HIGH error),

Treatment:

Device: NO error

Device: HIGH error

Device: LOW error