Trial Outcomes & Findings for Effect of Liraglutide on Automated Closed-loop Glucose Control in Type 1 Diabetes (NCT NCT01856790)

NCT ID: NCT01856790

Last Updated: 2020-01-30

Results Overview

peak post-prandial venous glucose levels obtained after breakfast, lunch, and dinner between closed loop (CL) alone and CL + liraglutide

• Recruitment status: COMPLETED
• Study phase: EARLY_PHASE1
• Target enrollment: 15 participants
• Primary outcome timeframe: 48 hours
• Results posted on: 2020-01-30

Participant Flow

Participant milestones

Measure	All Study Participants 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.
Closed Loop Control STARTED	15
Closed Loop Control COMPLETED	13
Closed Loop Control NOT COMPLETED	2
Closed Loop Control + Liraglutide STARTED	13
Closed Loop Control + Liraglutide COMPLETED	11
Closed Loop Control + Liraglutide NOT COMPLETED	2

Reasons for withdrawal

Measure	All Study Participants 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.
Closed Loop Control Withdrawal by Subject	2
Closed Loop Control + Liraglutide Withdrawal by Subject	2

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Baseline Subject Characteristics n=11 Participants 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.
Age, Continuous	22 years STANDARD_DEVIATION 3.4 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 48 hours

peak post-prandial venous glucose levels obtained after breakfast, lunch, and dinner between closed loop (CL) alone and CL + liraglutide

Outcome measures

Measure	Closed Loop Insulin Delivery n=11 Participants 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.	Closed Loop + Liraglutide n=11 Participants 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.
Peak Post-prandial Venous Glucose Levels	98 mg/dL Standard Error 24	76 mg/dL Standard Error 17

SECONDARY outcome

Timeframe: 5-hour post prandial period after breakfast, lunch, and dinner

Outcome measures

Measure	Closed Loop Insulin Delivery n=11 Participants 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.	Closed Loop + Liraglutide n=11 Participants 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.
the Incremental Meal-related Glucose Area Under Curve (AUC)	789 mg*hr/dL Standard Deviation 176	500 mg*hr/dL Standard Deviation 151

OTHER_PRE_SPECIFIED outcome

Timeframe: 24- hours

Outcome measures

Measure	Closed Loop Insulin Delivery n=11 Participants 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.	Closed Loop + Liraglutide n=11 Participants 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.
Mean 24-hour Glucose Levels	130 mg/dL Standard Deviation 51	135 mg/dL Standard Deviation 45

OTHER_PRE_SPECIFIED outcome

Timeframe: 5- hour postprandial period

Outcome measures

Measure	Closed Loop Insulin Delivery n=11 Participants 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.	Closed Loop + Liraglutide n=11 Participants 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.
Mean Time to Peak Post-meal Glucose Value	1.8 hours Standard Deviation 0.5	1.8 hours Standard Deviation 0.6

OTHER_PRE_SPECIFIED outcome

Timeframe: 8a.m.-11p.m.

Outcome measures

Measure	Closed Loop Insulin Delivery n=11 Participants 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.	Closed Loop + Liraglutide n=11 Participants 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.
Mean Daytime Glucose Levels	143 mg/dL Standard Deviation 55	146 mg/dL Standard Deviation 47

OTHER_PRE_SPECIFIED outcome

Timeframe: 5 hours

Outcome measures

Measure	Closed Loop Insulin Delivery n=10 Participants 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.	Closed Loop + Liraglutide n=10 Participants 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.
Incremental Glucagon Peak	29 pg/mL/min Standard Deviation 16	35 pg/mL/min Standard Deviation 20

OTHER_PRE_SPECIFIED outcome

Timeframe: 2 hours

Outcome measures

Measure	Closed Loop Insulin Delivery n=10 Participants 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.	Closed Loop + Liraglutide n=10 Participants 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.
AUC Plasma Glucagon During MMTT	1904 pg*min/mL Standard Deviation 651	1801 pg*min/mL Standard Deviation 906

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 hours

Outcome measures

Measure	Closed Loop Insulin Delivery n=11 Participants 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.	Closed Loop + Liraglutide n=11 Participants 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.
Differences in Daily Insulin Requirements	51.5 units Standard Deviation 14	37.5 units Standard Deviation 12.9

OTHER_PRE_SPECIFIED outcome

Timeframe: Average of the 5-hour post prandial period for breakfast, lunch, dinner combined

Outcome measures

Measure	Closed Loop Insulin Delivery n=11 Participants 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.	Closed Loop + Liraglutide n=11 Participants 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.
Prandial Insulin Delivery During Closed Loop Therapy	22.6 units Standard Deviation 8.4	16.3 units Standard Deviation 8.3

OTHER_PRE_SPECIFIED outcome

Timeframe: 11p.m.-6a.m.

Outcome measures

Measure	Closed Loop Insulin Delivery n=11 Participants 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.	Closed Loop + Liraglutide n=11 Participants 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.
Mean Nocturnal Glucose Levels	104 mg/dL Standard Deviation 23	113 mg/dL Standard Deviation 24

Adverse Events

Closed Loop Only

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Closed Loop + Liraglutide

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Closed Loop Only n=13 participants at risk 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	Closed Loop + Liraglutide n=11 participants at risk 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.
Gastrointestinal disorders gastrointestinal distress	0.00% 0/13 Adverse events were recorded in categories with gastrointestinal disorders encompassing nausea, decreased appetite, constipation, bloating and/or diarrhea	54.5% 6/11 Adverse events were recorded in categories with gastrointestinal disorders encompassing nausea, decreased appetite, constipation, bloating and/or diarrhea
Nervous system disorders headache	0.00% 0/13 Adverse events were recorded in categories with gastrointestinal disorders encompassing nausea, decreased appetite, constipation, bloating and/or diarrhea	54.5% 6/11 Adverse events were recorded in categories with gastrointestinal disorders encompassing nausea, decreased appetite, constipation, bloating and/or diarrhea

Additional Information

Dr. Jennifer Sherr

Yale University School of Medicine

Phone: 203-785-5831

Email: jennifer.sherr@yale.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place