Trial Outcomes & Findings for Role of Glucagon-Like Peptide-1 in Postprandial Hypoglycemia (NCT NCT01162499)

Last Updated: 2017-10-23

Results Overview

To examine the effect of Exendin-(9-39) on plasma glucose levels samples were collected at various time points before and during the infusion \[Exendin-(9-39) or vehicle\] including: 60 minutes before the start of the infusion, again at the start of the infusion (time 0), and then every 30 minutes until 3 hours after the start of the meal. Using this information, the mean plasma glucose area under the curve (AUC) from the start of the infusion to the end of the infusion (3 hours) was calculated for both doses of Exendin-(9-39) \[300pmol/kg/min \& 500pmol/kg/min\] and compared with the vehicle.

Recruitment status

COMPLETED

Study phase

Target enrollment

7 participants

Primary outcome timeframe

3 hours

Results posted on

2017-10-23

Participant Flow

Children were recruited from the Division of Endocrinology and Diabetes at The Children's Hospital of Philadelphia.

One subject signed consent but they were excluded from study participation after the study team was unable to establish IV access.

Participant milestones

Participant milestones
Measure	Exendin-(9-39) First, Then Vehicle After an overnight fast, an intravenous (IV) infusion of Exendin-(9-39) was started 1 hour prior to the meal challenge and continued for 4 hours. After the first hour of the infusion, subjects underwent a mixed meal tolerance test in which Pediasure (10cc/kg) was consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes. Blood samples were drawn during the infusion to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The Exendin-(9-39) dose for the first 3 subjects was 300pmol/kg/min and, as planned, it was increased to 500pmol/kg/min for subsequent subjects. The next day, all procedures were repeated except subjects received an IV infusion of normal saline (vehicle) over 4 hours.	Vehicle First, Then Exendin-(9-39) After an overnight fast, an intravenous (IV) infusion of normal saline (vehicle) was started 1 hour prior to the meal challenge and continued for 4 hours. After the first hour of the infusion, subjects underwent a mixed meal tolerance test in which Pediasure (10cc/kg) was consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes. Blood samples were drawn to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The next day, all procedures were repeated except subjects received an IV infusion of Exendin-(9-39) which was started 1 hour prior to the meal challenge and continued for 4 hours. The dose for the first 3 subjects was 300pmol/kg/min and, as planned, it was increased to 500pmol/kg/min for subsequent subjects.
Intervention 1 (4 Hours) STARTED	3	4
Intervention 1 (4 Hours) Received Intervention	3	3
Intervention 1 (4 Hours) COMPLETED	3	3
Intervention 1 (4 Hours) NOT COMPLETED	0	1
Intervention 2 (4 Hours) STARTED	3	3
Intervention 2 (4 Hours) COMPLETED	3	3
Intervention 2 (4 Hours) NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Exendin-(9-39) First, Then Vehicle After an overnight fast, an intravenous (IV) infusion of Exendin-(9-39) was started 1 hour prior to the meal challenge and continued for 4 hours. After the first hour of the infusion, subjects underwent a mixed meal tolerance test in which Pediasure (10cc/kg) was consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes. Blood samples were drawn during the infusion to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The Exendin-(9-39) dose for the first 3 subjects was 300pmol/kg/min and, as planned, it was increased to 500pmol/kg/min for subsequent subjects. The next day, all procedures were repeated except subjects received an IV infusion of normal saline (vehicle) over 4 hours.	Vehicle First, Then Exendin-(9-39) After an overnight fast, an intravenous (IV) infusion of normal saline (vehicle) was started 1 hour prior to the meal challenge and continued for 4 hours. After the first hour of the infusion, subjects underwent a mixed meal tolerance test in which Pediasure (10cc/kg) was consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes. Blood samples were drawn to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The next day, all procedures were repeated except subjects received an IV infusion of Exendin-(9-39) which was started 1 hour prior to the meal challenge and continued for 4 hours. The dose for the first 3 subjects was 300pmol/kg/min and, as planned, it was increased to 500pmol/kg/min for subsequent subjects.
Intervention 1 (4 Hours) Unable to establish IV access	0	1

Baseline Characteristics

Role of Glucagon-Like Peptide-1 in Postprandial Hypoglycemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Subject Population n=6 Participants All subjects enrolled and treated in the protocol served as their own control. Because of this and the small sample size, baseline characteristic data is presented together.
Age, Categorical <=18 years	6 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	5 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	6 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
Region of Enrollment United States	6 participants n=5 Participants
Previous Surgery Nissen fundoplication	5 participants n=5 Participants
Previous Surgery Gastric pull-through	1 participants n=5 Participants
Feeding Regimen Oral Only	2 participants n=5 Participants
Feeding Regimen Both Oral & Gastrostomy	3 participants n=5 Participants
Feeding Regimen Gastrostomy Only	1 participants n=5 Participants
Post-Prandial Hypoglycemia Treatment Acarbose	4 participants n=5 Participants
Post-Prandial Hypoglycemia Treatment Feeding	2 participants n=5 Participants
Post-Prandial Hypoglycemia Treatment Frequency Intermittent	3 participants n=5 Participants
Post-Prandial Hypoglycemia Treatment Frequency Frequent	3 participants n=5 Participants
Age at Post-Prandial Hypoglycemia Diagnosis Less than 1 year	1 participants n=5 Participants
Age at Post-Prandial Hypoglycemia Diagnosis Between 1-2 years	1 participants n=5 Participants
Age at Post-Prandial Hypoglycemia Diagnosis Between 2-3 years	1 participants n=5 Participants
Age at Post-Prandial Hypoglycemia Diagnosis Between 3-4 years	3 participants n=5 Participants

PRIMARY outcome

Timeframe: 3 hours

Population: Changes were compared between the two dose levels of Exendin-(9-39) of 300pmol/kg/min (3 subjects) and 500pmol/kg/min (3 subjects) were compared to the vehicle infusion (all 6 subjects).

Outcome measures

Outcome measures
Measure	Exendin-(9-39) 300pmol/kg/Min Dose n=3 Participants After an overnight fast, an intravenous (IV) infusion of Exendin-(9-39) was started 1 hour prior to the meal challenge and continued for 4 hours. After the first hour of the infusion, subjects underwent a mixed meal tolerance test in which Pediasure (10cc/kg) was consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes. Blood samples were drawn during the infusion to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The Exendin-(9-39) dose was 300pmol/kg/min, infused over 4 total hours.	Exendin-(9-39) 500pmol/kg/Min Dose n=3 Participants After an overnight fast, an intravenous (IV) infusion of Exendin-(9-39) was started 1 hour prior to the meal challenge and continued for 4 hours. After the first hour of the infusion, subjects underwent a mixed meal tolerance test in which Pediasure (10cc/kg) was consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes. Blood samples were drawn during the infusion to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The Exendin-(9-39) dose was 500pmol/kg/min, infused over 4 total hours.	Vehicle n=6 Participants After an overnight fast, an intravenous (IV) infusion of normal saline (vehicle) was started 1 hour prior to the meal challenge and continued for 4 hours. After the first hour of the infusion, subjects underwent a mixed meal tolerance test in which Pediasure (10cc/kg) was consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes. Blood samples were drawn during the infusion to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The vehicle was infused over 4 total hours.
Mean Plasma Glucose Area Under the Curve (AUC 0-3h)	22,192.5 mg*min/dl Standard Error 4,784.7	25,207.1 mg*min/dl Standard Error 1,157.5	21,715.9 mg*min/dl Standard Error 3,597.8

SECONDARY outcome

Timeframe: 3 hours

Population: Changes were compared between the two dose levels of Exendin-(9-39) of 300pmol/kg/min (3 subjects) and 500pmol/kg/min (3 subjects) were compared to the vehicle infusion (all 6 subjects).

To examine the effect of Exendin-(9-39) on plasma insulin levels, samples were collected at various time points before and during the infusion \[Exendin-(9-39) or vehicle\] including: 60 minutes before the start of the infusion, again at the start of the infusion (time 0), and then every 30 minutes until 3 hours after the start of the meal. Using this information, the mean plasma insulin area under the curve (AUC) from the start of the infusion to the end of the infusion (3 hours) was calculated for both doses of Exendin-(9-39) \[300pmol/kg/min \& 500pmol/kg/min\] and compared with the vehicle.

Outcome measures

Outcome measures
Measure	Exendin-(9-39) 300pmol/kg/Min Dose n=3 Participants After an overnight fast, an intravenous (IV) infusion of Exendin-(9-39) was started 1 hour prior to the meal challenge and continued for 4 hours. After the first hour of the infusion, subjects underwent a mixed meal tolerance test in which Pediasure (10cc/kg) was consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes. Blood samples were drawn during the infusion to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The Exendin-(9-39) dose was 300pmol/kg/min, infused over 4 total hours.	Exendin-(9-39) 500pmol/kg/Min Dose n=3 Participants After an overnight fast, an intravenous (IV) infusion of Exendin-(9-39) was started 1 hour prior to the meal challenge and continued for 4 hours. After the first hour of the infusion, subjects underwent a mixed meal tolerance test in which Pediasure (10cc/kg) was consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes. Blood samples were drawn during the infusion to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The Exendin-(9-39) dose was 500pmol/kg/min, infused over 4 total hours.	Vehicle n=6 Participants After an overnight fast, an intravenous (IV) infusion of normal saline (vehicle) was started 1 hour prior to the meal challenge and continued for 4 hours. After the first hour of the infusion, subjects underwent a mixed meal tolerance test in which Pediasure (10cc/kg) was consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes. Blood samples were drawn during the infusion to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The vehicle was infused over 4 total hours.
Mean Plasma Insulin Area Under the Curve (AUC 0-3h)	14,695.85 pmol*min/l Standard Error 12,662.9	9,058.5 pmol*min/l Standard Error 7,562.7	19,435.4 pmol*min/l Standard Error 10,392.6

SECONDARY outcome

Timeframe: 3 hours

Population: AUC were compared between the two dose levels of Exendin-(9-39) of 300pmol/kg/min (3 subjects) and 500pmol/kg/min (3 subjects) were compared to the vehicle infusion (all 6 subjects).

The effect of gastric emptying was examined using the acetaminophen method whereby acetaminophen (30mg/kg or maximum of 1500mg) was mixed into the Pediasure/formula during the meal tolerance testing. Blood samples were collected every 30 minutes and the absorption of acetaminophen was determined by the gastric emptying rate, as the serum concentrations correlate with gastric emptying of liquids. Mean acetaminophen levels for each group at each time point were used to calculate the Area Under the Concentration versus Time Curve (AUC expressed in μg\*min/l) after the consumption of formula for each of the two Exendin-(9-39) dose levels and normal saline vehicle.

Outcome measures

Outcome measures
Measure	Exendin-(9-39) 300pmol/kg/Min Dose n=3 Participants After an overnight fast, an intravenous (IV) infusion of Exendin-(9-39) was started 1 hour prior to the meal challenge and continued for 4 hours. After the first hour of the infusion, subjects underwent a mixed meal tolerance test in which Pediasure (10cc/kg) was consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes. Blood samples were drawn during the infusion to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The Exendin-(9-39) dose was 300pmol/kg/min, infused over 4 total hours.	Exendin-(9-39) 500pmol/kg/Min Dose n=3 Participants After an overnight fast, an intravenous (IV) infusion of Exendin-(9-39) was started 1 hour prior to the meal challenge and continued for 4 hours. After the first hour of the infusion, subjects underwent a mixed meal tolerance test in which Pediasure (10cc/kg) was consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes. Blood samples were drawn during the infusion to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The Exendin-(9-39) dose was 500pmol/kg/min, infused over 4 total hours.	Vehicle n=6 Participants After an overnight fast, an intravenous (IV) infusion of normal saline (vehicle) was started 1 hour prior to the meal challenge and continued for 4 hours. After the first hour of the infusion, subjects underwent a mixed meal tolerance test in which Pediasure (10cc/kg) was consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes. Blood samples were drawn during the infusion to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The vehicle was infused over 4 total hours.
Mean Acetaminophen Plasma Concentration Area Under the Curve (AUC 0-3h)	3,387.5 μg*min/l Standard Error 898	3,742.8 μg*min/l Standard Error 124.3	3,436.6 μg*min/l Standard Error 465.2

SECONDARY outcome

Timeframe: 60 minutes before the start of the infusion, again at the start of the infusion (time 0), and then every 30 minutes until 3 hours after the start of the infusion

Population: Differences were compared between the two dose levels of Exendin-(9-39) of 300pmol/kg/min (3 subjects) and 500pmol/kg/min (3 subjects) were compared to the vehicle infusion (all 6 subjects).

To examine the effect of Exendin-(9-39) on plasma glucagon-like peptide-1 levels, samples were collected at various time points before and during the infusion \[Exendin-(9-39) or vehicle\] including: 60 minutes before the start of the infusion, again at the start of the infusion (time 0), and then every 30 minutes until 3 hours after the start of the infusion. The mean peak glucagon-like peptide-1 concentration for both Exendin-(9-39) doses were compared with the peak glucagon-like peptide-1 during vehicle infusion.

Outcome measures

Outcome measures
Measure	Exendin-(9-39) 300pmol/kg/Min Dose n=3 Participants After an overnight fast, an intravenous (IV) infusion of Exendin-(9-39) was started 1 hour prior to the meal challenge and continued for 4 hours. After the first hour of the infusion, subjects underwent a mixed meal tolerance test in which Pediasure (10cc/kg) was consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes. Blood samples were drawn during the infusion to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The Exendin-(9-39) dose was 300pmol/kg/min, infused over 4 total hours.	Exendin-(9-39) 500pmol/kg/Min Dose n=3 Participants After an overnight fast, an intravenous (IV) infusion of Exendin-(9-39) was started 1 hour prior to the meal challenge and continued for 4 hours. After the first hour of the infusion, subjects underwent a mixed meal tolerance test in which Pediasure (10cc/kg) was consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes. Blood samples were drawn during the infusion to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The Exendin-(9-39) dose was 500pmol/kg/min, infused over 4 total hours.	Vehicle n=6 Participants After an overnight fast, an intravenous (IV) infusion of normal saline (vehicle) was started 1 hour prior to the meal challenge and continued for 4 hours. After the first hour of the infusion, subjects underwent a mixed meal tolerance test in which Pediasure (10cc/kg) was consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes. Blood samples were drawn during the infusion to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The vehicle was infused over 4 total hours.
Peak Plasma Glucagon-like Peptide-1 (GLP-1) Concentration During Infusion	65.8 pmol/l Standard Error 33.3	75.2 pmol/l Standard Error 5.8	72.8 pmol/l Standard Error 26.1

SECONDARY outcome

Timeframe: 60 minutes before the start of the infusion, again at the start of the infusion (time 0), and then every 30 minutes until 3 hours after the start of the infusion

Population: Differences in peak glucagon concentration were compared between the two dose levels of Exendin-(9-39) of 300pmol/kg/min (3 subjects) and 500pmol/kg/min (3 subjects) were compared to the vehicle infusion (all 6 subjects).

To examine the effect of Exendin-(9-39) on plasma glucagon levels, samples were collected at various 3 hours after the start of the infusion. The mean peak glucagon concentration for both Exendin-(9-39) doses were compared with the peak glucagon during vehicle infusion.

Outcome measures

Outcome measures
Measure	Exendin-(9-39) 300pmol/kg/Min Dose n=3 Participants After an overnight fast, an intravenous (IV) infusion of Exendin-(9-39) was started 1 hour prior to the meal challenge and continued for 4 hours. After the first hour of the infusion, subjects underwent a mixed meal tolerance test in which Pediasure (10cc/kg) was consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes. Blood samples were drawn during the infusion to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The Exendin-(9-39) dose was 300pmol/kg/min, infused over 4 total hours.	Exendin-(9-39) 500pmol/kg/Min Dose n=3 Participants After an overnight fast, an intravenous (IV) infusion of Exendin-(9-39) was started 1 hour prior to the meal challenge and continued for 4 hours. After the first hour of the infusion, subjects underwent a mixed meal tolerance test in which Pediasure (10cc/kg) was consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes. Blood samples were drawn during the infusion to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The Exendin-(9-39) dose was 500pmol/kg/min, infused over 4 total hours.	Vehicle n=6 Participants After an overnight fast, an intravenous (IV) infusion of normal saline (vehicle) was started 1 hour prior to the meal challenge and continued for 4 hours. After the first hour of the infusion, subjects underwent a mixed meal tolerance test in which Pediasure (10cc/kg) was consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes. Blood samples were drawn during the infusion to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The vehicle was infused over 4 total hours.
Peak Glucagon Concentration During Infusion	127.5 pg/ml Standard Error 75.7	145.7 pg/ml Standard Error 33.6	114.0 pg/ml Standard Error 50.1

Adverse Events

Exendin-(9-39) 300pmol/kg/Min Dose

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Exendin-(9-39) 500pmol/kg/Min Dose

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Vehicle

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Exendin-(9-39) 300pmol/kg/Min Dose n=3 participants at risk After an overnight fast, an intravenous (IV) infusion of Exendin-(9-39) was started 1 hour prior to the meal challenge and continued for 4 hours. After the first hour of the infusion, subjects underwent a mixed meal tolerance test in which Pediasure (10cc/kg) was consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes. Blood samples were drawn during the infusion to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The Exendin-(9-39) dose was 300pmol/kg/min, infused over 4 total hours.	Exendin-(9-39) 500pmol/kg/Min Dose n=3 participants at risk After an overnight fast, an intravenous (IV) infusion of Exendin-(9-39) was started 1 hour prior to the meal challenge and continued for 4 hours. After the first hour of the infusion, subjects underwent a mixed meal tolerance test in which Pediasure (10cc/kg) was consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes. Blood samples were drawn during the infusion to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The Exendin-(9-39) dose was 500pmol/kg/min, infused over 4 total hours.	Vehicle n=6 participants at risk After an overnight fast, an intravenous (IV) infusion of normal saline (vehicle) was started 1 hour prior to the meal challenge and continued for 4 hours. After the first hour of the infusion, subjects underwent a mixed meal tolerance test in which Pediasure (10cc/kg) was consumed by mouth or gastrostomy/nasogastric tube over a period of 15 minutes. Blood samples were drawn during the infusion to measure blood glucose, plasma insulin, glucagon and plasma glucagon-like-peptide-1 (GLP-1). The vehicle was infused over 4 total hours.
Musculoskeletal and connective tissue disorders Muscle Spasm	0.00% 0/3 • 30 days following the last administration of study treatment (either Exendin-(9-39) or vehicle)	0.00% 0/3 • 30 days following the last administration of study treatment (either Exendin-(9-39) or vehicle)	16.7% 1/6 • Number of events 1 • 30 days following the last administration of study treatment (either Exendin-(9-39) or vehicle)
Endocrine disorders Hypoglycemia	0.00% 0/3 • 30 days following the last administration of study treatment (either Exendin-(9-39) or vehicle)	0.00% 0/3 • 30 days following the last administration of study treatment (either Exendin-(9-39) or vehicle)	16.7% 1/6 • Number of events 1 • 30 days following the last administration of study treatment (either Exendin-(9-39) or vehicle)
Gastrointestinal disorders Gastrostomy-tube discharge	0.00% 0/3 • 30 days following the last administration of study treatment (either Exendin-(9-39) or vehicle)	0.00% 0/3 • 30 days following the last administration of study treatment (either Exendin-(9-39) or vehicle)	16.7% 1/6 • Number of events 1 • 30 days following the last administration of study treatment (either Exendin-(9-39) or vehicle)

Additional Information

Diva De Leon, MD

Children's Hospital of Philadelphia

Phone: 267-426-5529

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place