Congenital Hyperinsulinism
Conditions
Keywords
Hyperinsulinism, Hypoglycemia, KATP channel
Brief summary
The purpose of this study is to examine the effects of exendin-(9-39) on fasting blood glucose and protein induced hypoglycemia on subjects with Congenital Hyperinsulinism. Funding Source - FDA Office of Orphan Products Development (OODP).
Detailed description
This is a placebo controlled study with randomized crossover design to evaluate the effect of the glucagon-like peptide-1 (GLP-1) receptor antagonist, exendin-(9-39), on fasting blood glucose levels, protein-induced hypoglycemia, and fasting tolerance of subjects with congenital hyperinsulinism due to mutations in the ATP- sensitive potassium channel (KATP) channel.
Interventions
DRUGExendin-(9-39)
100-500pmol/kg/min
DRUGplacebo
placebo (0.9% NaCl)
Sponsors
Diva De Leon
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
In a random crossover design, subjects were assigned to either intervention (6 hour infusion of exendin( 9-39) at a dose range of 100-500pmol/kg/min) or vehicle (6hr infusion of 0.9%NaCl)
Eligibility
Sex/Gender
ALL
Age
6 Months to 18 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of hyperinsulinism * Mutation analysis results demonstrating KATP channel defect * Age 6 months to 18 years with * Persistent hypoglycemia
Exclusion criteria
* Current therapy with medications that may affect glucose metabolism such as octreotide, diazoxide, high dose glucocorticoids, adrenergic agents, etc. Subjects will be eligible to participate if the last dose of octreotide is given 48 hrs before study day 1 and the last dose of diazoxide is given 72 hours before study day 1 * Evidence of a medical condition that might alter results or compromised the elimination of the peptide, including active infection, kidney failure, severe liver dysfunction, severe respiratory or cardiac failure * Pregnancy * Subjects with milk protein allergy will be excluded for participating in studies involving protein tolerance test
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC) Plasma Glucose | Time 0 min - time 360 min | Area under the curve plasma glucose from the initiation of infusion of vehicle or exendin-(9-39) to end of the infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC) Plasma Insulin | time 0 min to time 360 min | Area under the curve plasma insulin from the initiation of infusion of vehicle or exendin-(9-39) to end of the infusion |
| Area Under the Curve (AUC) Plasma C-peptide | time 0 min to time 360 min | Area under the curve plasma C-peptide from the beginning of the infusion of vehicle or exendin-(9-39) to the end of the infusion |
| Area Under the Curve (AUC) Plasma Glucagon | time 0 min to time 360 min | Area under the curve plasma glucagon from the beginning of the infusion of vehicle or exendin-(9-39) to the end of the infusion |
| Area Under the Curve ( AUC) Plasma Total GLP-1 (Glucagon-like Peptide-1) | time 0 to time 360 min | Area under the curve plasma total GLP-1 (glucagon-like peptide-1) from the beginning of the infusion of vehicle or exendin-(9-39) to the end of the infusion |
| Area Under the Curve ( AUC) Plasma Active GLP-1 (Glucagon-like Peptide-1) | time 0 min to time 360 min | Area under the curve plasma active GLP-1 (glucagon-like peptide-1) from the beginning of the infusion of vehicle or exendin-(9-39) to the end of the infusion |
Countries
United States
Participant flow
Recruitment details
Subjects age 6months to 18 years with congenital hyperinsulinism due to mutations in the Katp channel( KatpHI) were recruited from the Hyperinsulinism Center at The Children's Hospital of Philadelphia
Pre-assignment details
17 subject were enrolled (consented). One(1) withdrawn
Participants by arm
| Arm | Count |
|---|---|
| Subject Population 9 subjects were randomized to the vehicle first arm and the next day they were switched to exendin- (9-39). 7 subjects were randomized to the exendin-(9-39) first arm and the next day they were switched to vehicle. 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. | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | Subject Population |
|---|---|
| Age, Categorical <=18 years | 16 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 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 | 1 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 | 15 Participants |
| Region of Enrollment United States | 16 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 12 / 16 | 8 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
Area Under the Curve (AUC) Plasma Glucose
Area under the curve plasma glucose from the initiation of infusion of vehicle or exendin-(9-39) to end of the infusion
Time frame: Time 0 min - time 360 min
Population: A total of 16 subjects were included in the analysis. 1 subject was withdrawn.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle | Area Under the Curve (AUC) Plasma Glucose | 26994.7 mg*min/dL | Standard Deviation 4219.8 |
| Exendin-(9-39) | Area Under the Curve (AUC) Plasma Glucose | 32122.2 mg*min/dL | Standard Deviation 6650.1 |
Secondary
Area Under the Curve ( AUC) Plasma Active GLP-1 (Glucagon-like Peptide-1)
Area under the curve plasma active GLP-1 (glucagon-like peptide-1) from the beginning of the infusion of vehicle or exendin-(9-39) to the end of the infusion
Time frame: time 0 min to time 360 min
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle | Area Under the Curve ( AUC) Plasma Active GLP-1 (Glucagon-like Peptide-1) | 1373.7 pmol*min/L | Standard Deviation 1044 |
| Exendin-(9-39) | Area Under the Curve ( AUC) Plasma Active GLP-1 (Glucagon-like Peptide-1) | 1432.9 pmol*min/L | Standard Deviation 1114.3 |
Secondary
Area Under the Curve (AUC) Plasma C-peptide
Area under the curve plasma C-peptide from the beginning of the infusion of vehicle or exendin-(9-39) to the end of the infusion
Time frame: time 0 min to time 360 min
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle | Area Under the Curve (AUC) Plasma C-peptide | 281.4 ng*min/mL | Standard Deviation 155.8 |
| Exendin-(9-39) | Area Under the Curve (AUC) Plasma C-peptide | 236.6 ng*min/mL | Standard Deviation 112.5 |
Secondary
Area Under the Curve (AUC) Plasma Glucagon
Area under the curve plasma glucagon from the beginning of the infusion of vehicle or exendin-(9-39) to the end of the infusion
Time frame: time 0 min to time 360 min
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle | Area Under the Curve (AUC) Plasma Glucagon | 22806.8 pg*min/mL | Standard Deviation 10210.3 |
| Exendin-(9-39) | Area Under the Curve (AUC) Plasma Glucagon | 23409.4 pg*min/mL | Standard Deviation 11396.1 |
Secondary
Area Under the Curve (AUC) Plasma Insulin
Area under the curve plasma insulin from the initiation of infusion of vehicle or exendin-(9-39) to end of the infusion
Time frame: time 0 min to time 360 min
Population: data from only 15 subjects because the values were below the level of detection for one subject.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle | Area Under the Curve (AUC) Plasma Insulin | 1578.7 uIU*min/mL | Standard Deviation 1089.9 |
| Exendin-(9-39) | Area Under the Curve (AUC) Plasma Insulin | 1284.5 uIU*min/mL | Standard Deviation 553.7 |
Secondary
Area Under the Curve ( AUC) Plasma Total GLP-1 (Glucagon-like Peptide-1)
Area under the curve plasma total GLP-1 (glucagon-like peptide-1) from the beginning of the infusion of vehicle or exendin-(9-39) to the end of the infusion
Time frame: time 0 to time 360 min
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle | Area Under the Curve ( AUC) Plasma Total GLP-1 (Glucagon-like Peptide-1) | 4899.3 pmol*min/L | Standard Deviation 2598.8 |
| Exendin-(9-39) | Area Under the Curve ( AUC) Plasma Total GLP-1 (Glucagon-like Peptide-1) | 5698.8 pmol*min/L | Standard Deviation 3484.8 |