Congenital Hyperinsulinism (CHI), Persistent Hyperinsulinemic Hypoglycemia of Infancy (PHHI)
Conditions
Keywords
Congenital Hyperinsulinism (CHI), hyperinsulinism, Persistent Hyperinsulinemic Hypoglycemia of Infancy (PHHI), CHI, PHHI, Pancreatectomy, 18F-DOPA, PET/CT scan
Brief summary
Children with congenital hyperinsulinism (CHI) have low blood sugar, and some of these children may require surgery to remove part or all of their pancreas. In this study, researchers will test how well a radioactive drug, 18-labeled L-fluorodeoxyphenylalanine (called F-DOPA) can detect a form of hyperinsulinism (focal HI) that may be cured by surgery. Eligible participants in this study will have positron emission tomography/computerized tomography (PET/CT) scans with F-DOPA prior to surgery.
Detailed description
For children with congenital hyperinsulinism (CHI), low blood sugar is caused by cells in the pancreas that release too much insulin. Some children with CHI have these cells throughout their pancreas (called diffuse disease); others have them located in specific areas of the pancreas (called focal disease). Children who have focal disease located in specific areas of the pancreas may be cured with surgery. F-DOPA is a radioactive drug that is picked up by these cells and used for positron emission tomography (or PET), an imaging technique used in nuclear medicine departments. In this study, researchers will validate the efficacy and safety of using PET/CT with F-DOPA in the pre-operative localization of focal disease in children with hyperinsulinism.
Interventions
DRUG18 F-DOPA
1 time injection of 0.08 - 0.16 mCi/kg of 18F-DOPA
Sponsors
University of Pennsylvania
Children's Hospital of Philadelphia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Infants and children with a clinical diagnosis of hyperinsulinism who are suspected to have focal disease and are surgical candidates for pancreatectomy
Exclusion criteria
* Pregnant or lactating females * Any other major illness or condition that might substantially increase the risk associated with the subject's participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Accuracy of 18F-DOPA PET/CT Scans to Detect Focal Lesions in Children With Congenital Hyperinsulinism | Surgery typically occured within a week post PET | To determine the sensitivity and specificity of 18F-DOPA PET/CT for the detection of a focal pancreatic lesion in infants and children with poorly controlled hyperinsulinemic hypoglycemia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety of 18F-DOPA PET/CT Scan - Number of Participants With Adverse Events | evaluated with 72 hours or prior to pancreatic surgery (if any) | To further evaluate the safety of 18-labeled L-fluorodeoxyphenylalanine (18F-DOPA) PET/CT imaging in infants and children with congenital hyperinsulinism \- subjects are monitored clinically for any signs or symptoms of adverse events for 72 hours post PET. Adverse events are documented and followed to resolution |
Countries
United States
Participant flow
Recruitment details
From January 2009 to July 2013, the study team recruited and enrolled 129 subjects referred to the Congenital Hyperinsulinism Center at the Children's Hospital of Philadelphia who were potential candidates for partial pancreatectomy surgery if focal lesions were suspected and were able to be localized.
Pre-assignment details
1 subject was enrolled into the study (informed consent signed), however, was deemed ineligible due to subsequent additional clinical information provided after consent but prior to scheduled PET study. . A second subject had two scans, but is only counted once in the final analysis. This accounts for the enrollment discrepancy (130 vs.128 described in the protocol section)
Participants by arm
| Arm | Count |
|---|---|
| (18F-DOPA) PET/CT Imaging vs Surgical Results 18 F-DOPA: 1 time injection of 0.08 - 0.16 mCi/kg of 18F-DOPA given 10-15 minutes prior image acquisition. | 128 |
| Total | 128 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Did not have surgery after PET | 9 |
Baseline characteristics
| Characteristic | (18F-DOPA) PET/CT Imaging vs Surgical Results |
|---|---|
| Age, Categorical <=18 years | 128 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 101 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 12 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 14 Participants |
| Race (NIH/OMB) White | 95 Participants |
| Region of Enrollment Australia | 1 participants |
| Region of Enrollment Canada | 4 participants |
| Region of Enrollment Israel | 1 participants |
| Region of Enrollment Paraguay | 1 participants |
| Region of Enrollment United States | 121 participants |
| Sex: Female, Male Female | 57 Participants |
| Sex: Female, Male Male | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 128 |
| other Total, other adverse events | 0 / 128 |
| serious Total, serious adverse events | 0 / 128 |
Outcome results
Primary
Accuracy of 18F-DOPA PET/CT Scans to Detect Focal Lesions in Children With Congenital Hyperinsulinism
To determine the sensitivity and specificity of 18F-DOPA PET/CT for the detection of a focal pancreatic lesion in infants and children with poorly controlled hyperinsulinemic hypoglycemia.
Time frame: Surgery typically occured within a week post PET
Population: A single F-DOPA PET/CT imaging study was performed and reported prior to surgery. This data includes surgical histopathology confirmed as focal or diffuse. 19 of the 119 participants with surgical results had atypical histopathology that did not fit the definition of either category and therefore are excluded from this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PET/CT Imaging vs Surgical Result | Accuracy of 18F-DOPA PET/CT Scans to Detect Focal Lesions in Children With Congenital Hyperinsulinism | True Negatives (PET diffuse/surgery diffuse) | 34 cases |
| PET/CT Imaging vs Surgical Result | Accuracy of 18F-DOPA PET/CT Scans to Detect Focal Lesions in Children With Congenital Hyperinsulinism | False negatives (PET diffuse/surgery focal): | 10 cases |
| PET/CT Imaging vs Surgical Result | Accuracy of 18F-DOPA PET/CT Scans to Detect Focal Lesions in Children With Congenital Hyperinsulinism | False positives (PET focal/surgery diffuse): | 4 cases |
| PET/CT Imaging vs Surgical Result | Accuracy of 18F-DOPA PET/CT Scans to Detect Focal Lesions in Children With Congenital Hyperinsulinism | True positives (PET focal/surgery focal): | 52 cases |
95% CI: [75.2, 97.1]
95% CI: [72.3, 92]
Secondary
Safety of 18F-DOPA PET/CT Scan - Number of Participants With Adverse Events
To further evaluate the safety of 18-labeled L-fluorodeoxyphenylalanine (18F-DOPA) PET/CT imaging in infants and children with congenital hyperinsulinism \- subjects are monitored clinically for any signs or symptoms of adverse events for 72 hours post PET. Adverse events are documented and followed to resolution
Time frame: evaluated with 72 hours or prior to pancreatic surgery (if any)
Population: all participants who had both PET and surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PET/CT Imaging vs Surgical Result | Safety of 18F-DOPA PET/CT Scan - Number of Participants With Adverse Events | 0 Participants |