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

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

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.

Study Overview

• Status: Completed
• Conditions: Persistent Hyperinsulinemic Hypoglycemia of Infancy (PHHI); Congenital Hyperinsulinism (CHI)
• Intervention / Treatment: Drug: 18 F-DOPA

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 Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Surgery typically occured within a week post PET

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	evaluated with 72 hours or prior to pancreatic surgery (if any)

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Collaborators: University of Pennsylvania
• Investigators: Principal Investigator: Lisa J States, MD, Children's Hospital of Philadelphia

Publications and helpful links

General Publications

• 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. doi: 10.1016/j.jpeds.2006.08.028.
• 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. doi: 10.1210/jc.2007-1637. Epub 2007 Sep 25.
• 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. doi: 10.1111/j.1460-9592.2007.02192.x.
• 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. doi: 10.1159/000095664. Epub 2006 Sep 12.
• 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.
• Laje P, States LJ, Zhuang H, Becker SA, Palladino AA, Stanley CA, Adzick NS. Accuracy of PET/CT Scan in the diagnosis of the focal form of congenital hyperinsulinism. J Pediatr Surg. 2013 Feb;48(2):388-93. doi: 10.1016/j.jpedsurg.2012.11.025.
• Laje P, Palladino AA, Bhatti TR, States LJ, Stanley CA, Adzick NS. Pancreatic surgery in infants with Beckwith-Wiedemann syndrome and hyperinsulinism. J Pediatr Surg. 2013 Dec;48(12):2511-6. doi: 10.1016/j.jpedsurg.2013.05.016.
• Peranteau WH, Palladino AA, Bhatti TR, Becker SA, States LJ, Stanley CA, Adzick NS. The surgical management of insulinomas in children. J Pediatr Surg. 2013 Dec;48(12):2517-24. doi: 10.1016/j.jpedsurg.2013.04.022.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): February 1, 2018

Study Registration Dates

• First Submitted: October 18, 2011
• First Submitted That Met QC Criteria: November 6, 2011
• First Posted (Estimate): November 9, 2011

Study Record Updates

• Last Update Posted (Actual): October 13, 2022
• Last Update Submitted That Met QC Criteria: October 11, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Pancreatectomy; 18F-DOPA; hyperinsulinism; PET/CT scan; Congenital Hyperinsulinism (CHI); Persistent Hyperinsulinemic Hypoglycemia of Infancy (PHHI); CHI; PHHI
• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Hypoglycemia; Hyperinsulinism; Congenital Hyperinsulinism; Nesidioblastosis
• Other Study ID Numbers: 08-006211