Phase II Safety and Efficacy Study of 18FDOPA PET-CT in Children With Hyperinsulinemic Hypoglycemia

• Sponsor: Children's Hospital of Philadelphia (Other)
• Overall Status: Completed
• CT.gov ID: NCT01468454
• Collaborator: University of Pennsylvania (Other)
• Enrollment: 130
• Location: 1
• Arm: 1
• Duration (Months): 109
• Patients Per Site Per Month: 1.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Congenital Hyperinsulinism (CHI); Persistent Hyperinsulinemic Hypoglycemia of Infancy (PHHI)	Drug: 18 F-DOPA	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 130 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: A Phase II Safety and Efficacy Study of 18F-L-Fluoro-DOPA PET/CT Scan Localization of Focal Pancreatic Lesions in Children With Hyperinsulinemic Hypoglycemia
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Feb 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: (18F-DOPA) PET/CT imaging Obtain safety and efficacy data on the use of 18-labeled L-fluorodeoxyphenylalanine (18F-DOPA) PET imaging in children with HI for the clinical indication of localizing a focal lesion	Drug: 18 F-DOPA; 1 time injection of 0.08 - 0.16 mCi/kg of 18F-DOPA; Other Names: 18FDOPA PET SCAN

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Children's Hospital of Philadelphia
• University of Pennsylvania

Investigators

• Principal Investigator: Lisa J States, MD, Children's Hospital of Philadelphia

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• The Congenital Hyperinsulinism Center at The Children's Hospital of Philadelphia

Publications

• Chevalme, Yanna-Marina et al. FDOPA-(18F): a PET radiopharmaceutical recently registered for diagnostic use in countries of the European Union. Braz. arch. biol. technol. [online]. 2007, vol.50, n.spe [cited 2011-10-06], pp. 77-90 . Available from: <http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-89132007000600009&lng=en&nrm=iso>. ISSN 1516-8913. http://dx.doi.org/10.1590/S1516-89132007000600009.
• Hardy OT, Hernandez-Pampaloni M, Saffer JR, Scheuermann JS, Ernst LM, Freifelder R, Zhuang H, MacMullen C, Becker S, Adzick NS, Divgi C, Alavi A, Stanley CA. Accuracy of [18F]fluorodopa positron emission tomography for diagnosing and localizing focal congenital hyperinsulinism. J Clin Endocrinol Metab. 2007 Dec;92(12):4706-11. Epub 2007 Sep 25.
• Hardy OT, Hernandez-Pampaloni M, Saffer JR, Suchi M, Ruchelli E, Zhuang H, Ganguly A, Freifelder R, Adzick NS, Alavi A, Stanley CA. Diagnosis and localization of focal congenital hyperinsulinism by 18F-fluorodopa PET scan. J Pediatr. 2007 Feb;150(2):140-5.
• Hardy OT, Litman RS. Congenital hyperinsulinism - a review of the disorder and a discussion of the anesthesia management. Paediatr Anaesth. 2007 Jul;17(7):616-21. Review.
• Peranteau WH, Ganguly A, Steinmuller L, Thornton P, Johnson MP, Howell LJ, Stanley CA, Adzick NS. Prenatal diagnosis and postnatal management of diffuse congenital hyperinsulinism: a case report. Fetal Diagn Ther. 2006;21(6):515-8. Epub 2006 Sep 12.

• Responsible Party: Lisa States, Principal Investigator, Children's Hospital of Philadelphia
• ClinicalTrials.gov Identifier: NCT01468454
• Other Study ID Numbers: 08-006211
• First Posted: Nov 9, 2011
• Last Update Posted: Oct 15, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by Lisa States, Principal Investigator, Children's Hospital of Philadelphia: Congenital Hyperinsulinism (CHI); hyperinsulinism; Persistent Hyperinsulinemic Hypoglycemia of Infancy (PHHI); CHI; PHHI; Pancreatectomy; 18F-DOPA; PET/CT scan
• Additional relevant MeSH terms: Congenital Hyperinsulinism; Hypoglycemia; Hyperinsulinism

Study Results

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 Detail	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)

Arm/Group Title	F-DOPA PET/CT Imaging vs Surgical Result
Arm/Group Description	18 F-DOPA: 1 time injection of 0.08 - 0.16 mCi/kg of 18F-DOPA given 10-15 minutes prior image acquisition.
Period Title: Overall Study
STARTED	128
PETs Completed	128
Had Both PET and Surgery	119
COMPLETED	119
NOT COMPLETED	9

Baseline Characteristics

Arm/Group Title	(18F-DOPA) PET/CT Imaging vs Surgical Results
Arm/Group Description	18 F-DOPA: 1 time injection of 0.08 - 0.16 mCi/kg of 18F-DOPA given 10-15 minutes prior image acquisition.
Overall Participants	128
Age (Count of Participants)
<=18 years	128 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	57 44.5%
Male	71 55.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	27 21.1%
Not Hispanic or Latino	101 78.9%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 2.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 3.1%
White	95 74.2%
More than one race	12 9.4%
Unknown or Not Reported	14 10.9%
Region of Enrollment (participants) [Number]
United States	121 94.5%
Canada	4 3.1%
Australia	1 0.8%
Israel	1 0.8%
Paraguay	1 0.8%

Outcome Measures

1. Primary Outcome

Title	Accuracy of 18F-DOPA PET/CT Scans to Detect Focal Lesions in Children With Congenital Hyperinsulinism
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	PET/CT Imaging vs Surgical Result
Arm/Group Description	PET/CT imaging results in patients with surgical histologic confirmation.
Measure Participants	100
True Negatives (PET diffuse/surgery diffuse)	34
False negatives (PET diffuse/surgery focal):	10
False positives (PET focal/surgery diffuse):	4
True positives (PET focal/surgery focal):	52

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PET/CT Imaging vs Surgical Result
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Specificity
	Estimated Value	89.5
	Confidence Interval	(2-Sided) 95%; 75.2 to 97.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PET/CT Imaging vs Surgical Result
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Sensitivity
	Estimated Value	83.9
	Confidence Interval	(2-Sided) 95%; 72.3 to 92
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Safety of 18F-DOPA PET/CT Scan - Number of Participants With Adverse Events
Description	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)

Outcome Measure Data

Analysis Population Description

all participants who had both PET and surgery

Arm/Group Title	(18F-DOPA) PET/CT Imaging
Arm/Group Description	Obtain safety and efficacy data on the use of 18-labeled L-fluorodeoxyphenylalanine (18F-DOPA) PET imaging in children with HI for the clinical indication of localizing a focal lesion 18 F-DOPA: 1 time injection of 0.08 - 0.16 mCi/kg of 18F-DOPA
Measure Participants	119
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	reviewed within 72 hours post PET or prior to pancreatic surgery (which ever was first)
Adverse Event Reporting Description	included all participants who had PET (whether or not they also had surgery)
Arm/Group Title	(18F-DOPA) PET/CT Imaging
Arm/Group Description	Obtain safety and efficacy data on the use of 18-labeled L-fluorodeoxyphenylalanine (18F-DOPA) PET imaging in children with HI for the clinical indication of localizing a focal lesion 18 F-DOPA: 1 time injection of 0.08 - 0.16 mCi/kg of 18F-DOPA
All Cause Mortality
	(18F-DOPA) PET/CT Imaging
	Affected / at Risk (%)	# Events
Total	0/128 (0%)
Serious Adverse Events
	(18F-DOPA) PET/CT Imaging
	Affected / at Risk (%)	# Events
Total	0/128 (0%)
Other (Not Including Serious) Adverse Events
	(18F-DOPA) PET/CT Imaging
	Affected / at Risk (%)	# Events
Total	0/128 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.