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

"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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Device: ePID closed loop system; Drug: liraglutide

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Closed Loop Insulin Delivery; 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; Insulin pump controlled by closed loop unit and algorithm; Drug: liraglutide; Liraglutide is a long-acting analog of human glucagon like peptide-1 (GLP-1) that works as a GLP-1 receptor agonist; Other Names: Victoza

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Time Frame
Mean 24-hour Glucose Levels	24- hours
Mean Time to Peak Post-meal Glucose Value	5- hour postprandial period
Mean Daytime Glucose Levels	8a.m.-11p.m.
Incremental Glucagon Peak	5 hours
AUC Plasma Glucagon During MMTT	2 hours
Differences in Daily Insulin Requirements	24 hours
Prandial Insulin Delivery During Closed Loop Therapy	Average of the 5-hour post prandial period for breakfast, lunch, dinner combined
Mean Nocturnal Glucose Levels	11p.m.-6a.m.

Collaborators and Investigators

• Sponsor: Jennifer Sherr
• Collaborators: Yale University; Juvenile Diabetes Research Foundation
• Investigators: Principal Investigator: Jennifer Sherr, MD, PhD, Yale University

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: May 14, 2013
• First Submitted That Met QC Criteria: May 14, 2013
• First Posted (Estimate): May 17, 2013

Study Record Updates

• Last Update Posted (Actual): January 30, 2020
• Last Update Submitted That Met QC Criteria: January 28, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide
• Other Study ID Numbers: 1211011156