Clinical trial NCT01856790: Effect of Liraglutide on Automated Closed-loop Glucose Control in Type 1 Diabetes
Official title: Effect of Liraglutide on Automated Closed-loop Glucose Control in Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Type 1 Diabetes
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Juvenile Diabetes Research Foundation
name: Yale University
First posted: 2013-05-17
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: "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: 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.

Eligibility criteria: Inclusion Criteria:

1. age 18-40 years
2. clinical diagnosis of Type 1 diabetes (T1D) (formal antibody and/or genetic testing will not be required)
3. duration of T1D ≥ 1 year
4. HbA1c ≤ 9 %
5. Treated with CSII for at least 3 months
6. Body weight \> 50 kg (to accommodate phlebotomy)
7. 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:

1. Insulin resistant (defined as requiring \> 1.5 units/kg/day at time of study enrollment)
2. Presence of any medical or psychiatric disorder that may interfere with subject safety or study conduct
3. 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
4. History of hypoglycemic seizure within last 3 months
5. Anemic (low hematocrit), evidence of renal insufficiency (elevated serum creatinine, BUN) or elevated liver function tests.
6. Female subjects who are pregnant, lactating, or unwilling to be tested for pregnancy
7. History of celiac disease gastroparesis, gastroesophageal reflux disease (GERD), disorder of gastric emptying, or disorder of intestinal motility
8. Taking a medication known to affect gastric motility
9. History of pancreatitis, gallstones, alcoholism or high triglyceride levels
10. Personal or family history of thyroid cancer or multiple endocrine neoplasia type 2 (MEN2)
11. Subjects unable to give consent

Primary outcomes:
measure: Peak Post-prandial Venous Glucose Levels
timeFrame: 48 hours
Secondary outcomes:
measure: the Incremental Meal-related Glucose Area Under Curve (AUC)
timeFrame: 5-hour post prandial period after breakfast, lunch, and dinner
Other outcomes:
measure: Mean 24-hour Glucose Levels
timeFrame: 24- hours
measure: Mean Time to Peak Post-meal Glucose Value
timeFrame: 5- hour postprandial period
measure: Mean Daytime Glucose Levels
timeFrame: 8a.m.-11p.m.
measure: Incremental Glucagon Peak
timeFrame: 5 hours
measure: AUC Plasma Glucagon During MMTT
timeFrame: 2 hours
measure: Differences in Daily Insulin Requirements
timeFrame: 24 hours
measure: Prandial Insulin Delivery During Closed Loop Therapy
timeFrame: Average of the 5-hour post prandial period for breakfast, lunch, dinner combined
measure: Mean Nocturnal Glucose Levels
timeFrame: 11p.m.-6a.m.
Locations:
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
Study officials:
affiliation: Yale University
name: Jennifer Sherr, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: