Effect of Liraglutide on Automated Closed-loop Glucose Control in Type 1 Diabetes

Study Overview
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Brief Summary
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Closed loop artificial pancreas systems have been under development for the control of blood sugars in those living with diabetes. These systems consist of a continuous glucose sensor, which sends a signal to a computer program that automatically determines how much insulin to give. The computer program then tells an insulin pump to deliver the insulin. While such systems have been tested under a number of conditions, post-meal blood sugars are difficult to control. This study is designed to see if liraglutide, a glucagon like peptide receptor agonist, can help minimize the post meal blood sugar spikes in subjects with type 1 diabetes while they are on a closed loop system.

Detailed Description
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Open-label, crossover study comparing the peak post-prandial glucose levels and the incremental post-prandial glucose area under the curve (AUC) during closed loop (CL) control alone and during CL control with liraglutide in an inpatient research setting. Data generated during outpatient baseline evaluation and liraglutide dose titration phases of the study will be compared to assess the short-term efficacy of this agent during open-loop continuous subcutaneous insulin infusion (CSII) pump treatment.

Official Title
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Effect of Liraglutide on Automated Closed-loop Glucose Control in Type 1 Diabetes

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Device: ePID closed loop system
* Drug: liraglutide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18-40 years clinical diagnosis of Type 1 diabetes (T1D) (formal antibody and/or genetic testing will not be required) duration of T1D ≥ 1 year HbA1c ≤ 9 % Treated with CSII for at least 3 months Body weight > 50 kg (to accommodate phlebotomy) Be in good general health without other medical or psychiatric illnesses that would, in the judgment of the investigator, interfere with subject safety or study conduct Exclusion Criteria: Insulin resistant (defined as requiring > 1.5 units/kg/day at time of study enrollment) Presence of any medical or psychiatric disorder that may interfere with subject safety or study conduct Use of any medications (besides insulin) known to blood glucose levels, including oral or other systemic glucocorticoid therapy. Inhaled, intranasal, or rectal corticosteroid use is allowed along as not given within 4 weeks of admission to the hospital research unit (HRU). Use of topical glucocorticoids is allowable as long as affected skin area does not overlap with study device sites. Subjects using herbal supplements will be excluded, due to the unknown effects of these supplements on glucose control History of hypoglycemic seizure within last 3 months Anemic (low hematocrit), evidence of renal insufficiency (elevated serum creatinine, BUN) or elevated liver function tests. Female subjects who are pregnant, lactating, or unwilling to be tested for pregnancy History of celiac disease gastroparesis, gastroesophageal reflux disease (GERD), disorder of gastric emptying, or disorder of intestinal motility Taking a medication known to affect gastric motility History of pancreatitis, gallstones, alcoholism or high triglyceride levels Personal or family history of thyroid cancer or multiple endocrine neoplasia type 2 (MEN2) Subjects unable to give consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Closed Loop Insulin Delivery<br>Each participant recruited into the study will undergo two inpatient closed loop admissions. The first admission will be utilizing closed loop control alone, using the Medtronic external Physiological Insulin Delivery (ePID) algorithm. The ePID controller uses a proportional-integral-derivative algorithm modified to include insulin feedback. Following the first closed loop admission, each participant is initiated on adjunctive once daily liraglutide therapy. They undergo a 3-4 week dose titration period. Participants are then admitted for a second closed loop admission to assess the combined effects of closed loop control with adjunctive once daily liraglutide therapy. | Device: ePID closed loop system<br>* Insulin pump controlled by closed loop unit and algorithm<br>Drug: liraglutide<br>* Liraglutide is a long-acting analog of human glucagon like peptide-1 (GLP-1) that works as a GLP-1 receptor agonist<br>* Other names: Victoza;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Post-prandial Venous Glucose Levels | peak post-prandial venous glucose levels obtained after breakfast, lunch, and dinner between closed loop (CL) alone and CL + liraglutide | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the Incremental Meal-related Glucose Area Under Curve (AUC) |  | 5-hour post prandial period after breakfast, lunch, and dinner |