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| ID | Type | Description | Link |
|---|---|---|---|
| R01FD004905 | Other Grant/Funding Number | US Food and Drug Administration |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vehicle first, then Exendin-(9-39) | Other | An infusion of vehicle (0.9%NaCl) will run for 60 minutes(time -60 to 0) before starting the study infusion of vehicle or exendin-(9-39). At time 0, vehicle (0.9%NaCl) will be started and will continue for 6 hours. The following day, at time 0, exendin-(9-39) at a dose ranging from 100-500pmol/kg/min will be started and continue for 6 hours. During both infusions, blood glucose, insulin, c-peptide, GLP-1, and glucagon will be measured every 30 minutes. |
|
| Exendin-(9-39) first then Vehicle. | Other | An infusion of vehicle (0.9%NaCl) will run for 60 minutes(time -60 to 0) before starting the study infusion of vehicle or exendin-(9-39). . At time 0, exendin-(9-39) at a dose ranging from 100-500pmol/kg/min will be started and continue for 6 hours. The following day, at time 0, vehicle (0.9%NaCl) will be started and will continue for 6 hours. During both infusions, blood glucose, insulin, c-peptide, GLP-1, and glucagon will be measured every 30 minutes. . |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Exendin-(9-39) | Drug | 100-500pmol/kg/min |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 0 min - time 360 min |
| Measure | Description | Time Frame |
|---|---|---|
| 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 0 min to time 360 min |
| Area Under the Curve (AUC) Plasma C-peptide |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Diva D DeLeon, MD | Children's Hospital of Philadelphia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35416981 | Derived | Stefanovski D, Vajravelu ME, Givler S, De Leon DD. Exendin-(9-39) Effects on Glucose and Insulin in Children With Congenital Hyperinsulinism During Fasting and During a Meal and a Protein Challenge. Diabetes Care. 2022 Jun 2;45(6):1381-1390. doi: 10.2337/dc21-2009. |
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17 subject were enrolled (consented). One(1) withdrawn
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
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| ID | Title | Description |
|---|---|---|
| FG000 | Vehicle First Then Exendin-(9-39) | An infusion of vehicle (0.9%NaCl) will run for 60 minutes(time -60 to 0) before starting the study infusion of vehicle or exendin-(9-39). At time 0, vehicle (0.9%NaCl) will be started and will continue for 6 hours. The following day, at time 0, exendin-(9-39) at a dose ranging from 100-500pmol/kg/min will be started and continue for 6 hours. During both infusions, blood glucose, insulin, c-peptide, glucagon-like peptide-(GLP-1) , and glucagon will be measured every 30 minutes. Vehicle: (0.9% NaCl) |
| FG001 | Exendin-(9-39) First Then Vehicle | An infusion of vehicle (0.9%NaCl) will run for 60 minutes(time -60 to 0) before starting the study infusion of vehicle or exendin-(9-39). At time 0, exendin-(9-39) at a dose ranging from 100-500pmol/kg/min will be started and continue for 6 hours. The following day, at time 0, vehicle (0.9%NaCl) will be started and will continue for 6 hours. During both infusions, blood glucose, insulin, c-peptide, glucagon-like peptide-(GLP-1) , and glucagon will be measured every 30 minutes. Exendin-(9-39): 100-500pmol/kg/min |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Intervention 1(6 Hours) |
| |||||||||||||
| Intervention 2(6 Hours) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | A total of 16 subjects were included in the analysis. 1 subject was withdrawn. | Posted | Mean | Standard Deviation | mg*min/dL | Time 0 min - time 360 min |
|
baseline to 24 hours after the end of study of infusion.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Vehicle | Subjects received an infusion of vehicle (0.9% NaCl) intravenously from time 0 min to time 360 min Vehicle: (0.9% NaCl) |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| hypoglycemia | Endocrine disorders | Systematic Assessment |
For safety reasons, blood glucose levels were maintained above a safety threshold (55-60mg/dL) during the study by infusing dextrose intravenously which may limit the magnitude of the effect that we will be able to detect.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Diva DeLeon, MD | The Children's Hospital of Philadelphia | 267-426-5529 | deleon@email.chop.edu |
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| ID | Term |
|---|---|
| D044903 | Congenital Hyperinsulinism |
| D006946 | Hyperinsulinism |
| D007003 | Hypoglycemia |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D007232 | Infant, Newborn, Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| ID | Term |
|---|---|
| C083773 | exendin (9-39) |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
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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)
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| placebo | Drug | placebo (0.9% NaCl) |
|
|
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 0 min to time 360 min |
| 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 0 min to time 360 min |
| 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 0 to time 360 min |
| 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 0 min to time 360 min |
| NOT COMPLETED |
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| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| 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 | data from only 15 subjects because the values were below the level of detection for one subject. | Posted | Mean | Standard Deviation | uIU*min/mL | time 0 min to time 360 min |
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|
|
| 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 | Posted | Mean | Standard Deviation | ng*min/mL | time 0 min to time 360 min |
|
|
|
| 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 | Posted | Mean | Standard Deviation | pg*min/mL | time 0 min to time 360 min |
|
|
|
| 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 | Posted | Mean | Standard Deviation | pmol*min/L | time 0 to time 360 min |
|
|
|
| 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 | Posted | Mean | Standard Deviation | pmol*min/L | time 0 min to time 360 min |
|
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|
| 0 |
| 16 |
| 0 |
| 16 |
| 12 |
| 16 |
| EG001 | Exendin-(9-39) | Subjects received an infusion of exendin-(9-39) intravenously at a dose ranging from 100-500pmol/kg/min from time 0 min to time 360 min Exendin-(9-39) | 0 | 16 | 0 | 16 | 8 | 16 |
| hyperglycemia | Endocrine disorders | Systematic Assessment |
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| Emesis | Gastrointestinal disorders | Systematic Assessment |
|
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| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |