Type 1 Diabetes
Conditions
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.
Interventions
DEVICEePID closed loop system
Insulin pump controlled by closed loop unit and algorithm
DRUGliraglutide
Liraglutide is a long-acting analog of human glucagon like peptide-1 (GLP-1) that works as a GLP-1 receptor agonist
Sponsors
Juvenile Diabetes Research Foundation
Yale University
Jennifer Sherr
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak Post-prandial Venous Glucose Levels | 48 hours | peak post-prandial venous glucose levels obtained after breakfast, lunch, and dinner between closed loop (CL) alone and CL + liraglutide |
Secondary
| Measure | Time frame |
|---|---|
| the Incremental Meal-related Glucose Area Under Curve (AUC) | 5-hour post prandial period after breakfast, lunch, and dinner |
Other
| Measure | Time frame |
|---|---|
| Mean Daytime Glucose Levels | 8a.m.-11p.m. |
| Incremental Glucagon Peak | 5 hours |
| AUC Plasma Glucagon During MMTT | 2 hours |
| Mean 24-hour Glucose Levels | 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. |
| Differences in Daily Insulin Requirements | 24 hours |
| Mean Time to Peak Post-meal Glucose Value | 5- hour postprandial period |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Baseline Subject Characteristics 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. | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Closed Loop Control | Withdrawal by Subject | 2 |
| Closed Loop Control + Liraglutide | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Baseline Subject Characteristics |
|---|---|
| Age, Continuous | 22 years STANDARD_DEVIATION 3.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 13 | 6 / 11 |
| serious Total, serious adverse events | 0 / 13 | 0 / 11 |
Outcome results
Primary
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
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Insulin Delivery | Peak Post-prandial Venous Glucose Levels | 98 mg/dL | Standard Error 24 |
| Closed Loop + Liraglutide | Peak Post-prandial Venous Glucose Levels | 76 mg/dL | Standard Error 17 |
p-value: 0.05Wilcoxon Matched Pairs signed rank tests
Secondary
the Incremental Meal-related Glucose Area Under Curve (AUC)
Time frame: 5-hour post prandial period after breakfast, lunch, and dinner
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Insulin Delivery | the Incremental Meal-related Glucose Area Under Curve (AUC) | 789 mg*hr/dL | Standard Deviation 176 |
| Closed Loop + Liraglutide | the Incremental Meal-related Glucose Area Under Curve (AUC) | 500 mg*hr/dL | Standard Deviation 151 |
p-value: 0.002Wilcoxon Matched Pairs signed rank tests
Other Pre-specified
AUC Plasma Glucagon During MMTT
Time frame: 2 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Insulin Delivery | AUC Plasma Glucagon During MMTT | 1904 pg*min/mL | Standard Deviation 651 |
| Closed Loop + Liraglutide | AUC Plasma Glucagon During MMTT | 1801 pg*min/mL | Standard Deviation 906 |
Other Pre-specified
Differences in Daily Insulin Requirements
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Insulin Delivery | Differences in Daily Insulin Requirements | 51.5 units | Standard Deviation 14 |
| Closed Loop + Liraglutide | Differences in Daily Insulin Requirements | 37.5 units | Standard Deviation 12.9 |
p-value: 0.001Wilcoxon Matched Pairs signed rank tests
Other Pre-specified
Incremental Glucagon Peak
Time frame: 5 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Insulin Delivery | Incremental Glucagon Peak | 29 pg/mL/min | Standard Deviation 16 |
| Closed Loop + Liraglutide | Incremental Glucagon Peak | 35 pg/mL/min | Standard Deviation 20 |
Other Pre-specified
Mean 24-hour Glucose Levels
Time frame: 24- hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Insulin Delivery | Mean 24-hour Glucose Levels | 130 mg/dL | Standard Deviation 51 |
| Closed Loop + Liraglutide | Mean 24-hour Glucose Levels | 135 mg/dL | Standard Deviation 45 |
Other Pre-specified
Mean Daytime Glucose Levels
Time frame: 8a.m.-11p.m.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Insulin Delivery | Mean Daytime Glucose Levels | 143 mg/dL | Standard Deviation 55 |
| Closed Loop + Liraglutide | Mean Daytime Glucose Levels | 146 mg/dL | Standard Deviation 47 |
Other Pre-specified
Mean Nocturnal Glucose Levels
Time frame: 11p.m.-6a.m.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Insulin Delivery | Mean Nocturnal Glucose Levels | 104 mg/dL | Standard Deviation 23 |
| Closed Loop + Liraglutide | Mean Nocturnal Glucose Levels | 113 mg/dL | Standard Deviation 24 |
Other Pre-specified
Mean Time to Peak Post-meal Glucose Value
Time frame: 5- hour postprandial period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Insulin Delivery | Mean Time to Peak Post-meal Glucose Value | 1.8 hours | Standard Deviation 0.5 |
| Closed Loop + Liraglutide | Mean Time to Peak Post-meal Glucose Value | 1.8 hours | Standard Deviation 0.6 |
p-value: 0.97Wilcoxon Matched Pairs signed rank tests
Other Pre-specified
Prandial Insulin Delivery During Closed Loop Therapy
Time frame: Average of the 5-hour post prandial period for breakfast, lunch, dinner combined
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Insulin Delivery | Prandial Insulin Delivery During Closed Loop Therapy | 22.6 units | Standard Deviation 8.4 |
| Closed Loop + Liraglutide | Prandial Insulin Delivery During Closed Loop Therapy | 16.3 units | Standard Deviation 8.3 |
p-value: 0.005Wilcoxon Matched Pairs signed rank tests