Fluorodopa F 18 in Congenital Hyperinsulinism

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Cook Children's Health Care System
Sponsor:
Information provided by (Responsible Party):
Cook Children's Health Care System
ClinicalTrials.gov Identifier:
NCT02021604
First received: December 20, 2013
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

Low blood sugars are known to cause brain damage in newborn babies. One of the most common causes of low blood sugars persisting beyond the new born period is a condition called congenital hyperinsulinism (HI). This is a disease whereby the pancreas secretes too much insulin and causes low blood sugars. Twenty to forty percent of these babies will have brain damage. There are two forms of this disease. In one form only a small part of the pancreas makes too much insulin (focal HI) and in the other, the whole pancreas make too much insulin (diffuse HI). If a surgeon could know which part of the pancreas has the focal lesion he could remove it and cure the patient.

The purpose of this study is to investigate whether a new investigational drug called Fluorodopa F 18, when used with a PET scan, can find the focal lesion and guide the surgeon to remove it, thus curing the patient and preventing further brain damage


Condition Intervention Phase
Congenital Hyperinsulinism
Drug: Fluorodopa F 18
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Diagnostic
Official Title: The Use of Fluorodopa F 18 Positron Emission Tomography Combined With Computed Tomography in Congenital Hyperinsulinism

Resource links provided by NLM:


Further study details as provided by Cook Children's Health Care System:

Primary Outcome Measures:
  • Positron Emission Tomography [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]
    Positron Emission Tomography will be used to determine whether or not the uptake of a radiopharmaceutical agent, Fluorodopa F 18, produced in a cyclotron located at a distance far from the imaging center will produce qualitatively adequate pancreatic images in patients with congenital hyperinsulinism

  • Comparative evaluation of PET image and surgical pathology map [ Time Frame: up to one month ] [ Designated as safety issue: No ]
    Investigators will directly compare pancreatic images from Fluorodopa F 18 PET combined with Computed Tomography versus the gold-standard of histopathological findings at surgery in subjects who received a partial or complete pancreatectomy


Estimated Enrollment: 50
Study Start Date: December 2013
Estimated Study Completion Date: June 2019
Estimated Primary Completion Date: January 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pancreatic Imaging with Fluorodopa F 18 Drug: Fluorodopa F 18
A dose of Fluorodopa F 18, 3-6 MBq/Kg (0.08-0.16 mCi/kg), will be injected intravenously into the subject under the direct supervision of the radiology sub-investigator. Then, the PET imaging procedure will begin and proceed for up to 70 minutes after injection. An abdominal CT image will be made using intravenous contrast. Both images, PET and CT, will be co-localized by the radiologist for interpretation.
Other Names:
  • Fluorodopa 18F (International Non-Proprietary Name)
  • 6-[18F]fluorolevodopa (U.S. Pharmacopeia)
  • Fluorodopa F 18 (CAS Number 75290-51-6)

Detailed Description:

Congenital Hyperinsulinism (HI) is a disorder of insulin secretion that causes profound hypoglycemia leading to significant morbidity. It is the most common form of persistent neonatal hypoglycemia, and the most dangerous. Inappropriate insulin secretion causes not only hypoglycemia but also inability to release free fatty acids from adipose tissue and inability to release glycogen from the liver. Hence the brain is deprived of all the major fuel sources (glucose, beta-hydroxybutyrate and lactate) for energy thus leading to the high incidence of brain damage. In up to 50% of cases of congenital hyperinsulinism, medical therapy fails and surgical resection of the pancreas is necessary. Previous techniques developed to differentiate those patients with focal HI in whom surgery could result in a cure are very invasive and put the infants at risk for hypoglycemic brain damage or arterial thrombosis.

It is known that the beta cells in the pancreatic islets, similar to other neuroendocrine tissues, contain amino acid decarboxylase (AADC). Beta cells take up L-Dopa and convert it into dopamine by AADC. It was proposed that as other neuroendocrine tumors such as phaeochromocytoma and carcinoid tumors express AADC and can be very easily visualized using Fluorodopa F 18 PET then so also would the pancreas be easily and accurately visualized. After initial reports demonstrated the effectiveness, safety and accuracy, there have been now over 200 patients with HI reported in the literature who have had Fluorodopa F 18 PET scans with suggestions that referral to major HI centers for Fluorodopa F 18 PET CT is now an integral part of standard of care management of patients with HI that require surgery. Fluorodopa F 18 PET scanning for patients with Hyperinsulinism is now established in Europe and Australia, and has close to 95% sensitivity. When linked to Computed Tomography (CT) image of the pancreas, Fluorodopa F 18 PET allows the surgeon to image the pancreas in three dimensions, to even more accurately identify the site of the focal lesion, increasing the chance of a sufficient partial pancreatectomy to cure the patient.

The objectives of this study are:

  1. To determine, using Positron Emission Tomography, the qualitative uptake of a radiopharmaceutical agent, Fluorodopa F 18, produced at a distance far from the imaging center, in the pancreas of patients with congenital hyperinsulinism.
  2. To determine whether, using a method of Computed Tomography Scanning combined with Fluorodopa F 18 pancreatic imaging will match the surgical histopathological findings of focal vs. diffuse islet cell abnormalities in patients with congenital hyperinsulinism who receive partial or complete pancreatectomy to treat their disease.
  Eligibility

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with HI attending the Cook Children's Congenital Hyperinsulinism Center and being treated by an Endocrinologist which may be the PI or a partner of this clinician.
  • The patient's Endocrinologist has determined that the patient cannot be safely managed with standard medical therapy (failed) and surgery is recommended to prevent future episodes of severe hypoglycemia and preserve brain function. Failure of medical therapy is defined as both:

    • Hypoglycemia (blood glucose <70 m/dL) on a single measure despite the use of anti-hypoglycemic medications, if applicable to the individual patient, including and limited to diazoxide or octreotide
    • Inability to fast, defined as the inability to maintain a blood glucose >50 mg/dL for: 1) more than 12 hours for infants < 1 year of age; 2) more than 15 hours 1-3 years of age; 3) more than 18 hours over 3 years of age
  • Patients in whom the genetic testing (if available and informative) does not prove diffuse HI disease. Such children might be considered if they have one or more of the following situations:

    • no genetic testing results (e.g., due to insurance denial or parental refusal)
    • negative genetic testing (note: only 75% of mutations may be found with existing technology)
    • no autosomal recessive mutations in ABCC8 or KCNJ11 on the maternal allele
    • no autosomal dominant mutations in ABCC8 or KCNJ11
  • Patients thought to have focal HI disease based on genetic testing and have well-controlled blood glucose levels with any degree of dietary or medical management, BUT the patient and their parent(s) or LAR wishes to proceed with surgery for a possible cure of HI disease.

Exclusion Criteria:

  • Patients who do not have a diagnosis of HI
  • Patients with genetic evidence of diffuse HI
  • Patients who are pregnant
  • Nursing mothers who are unwilling to discontinue breastfeeding their infant for 48 hours after Fluorodopa F 18 injection
  • Patients with a known allergy to Fluorodopa F 18 agent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02021604

Contacts
Contact: Heather Urbanek, CRC 682885-7208 heather.urbanek@cookchildrens.org

Locations
United States, Texas
Cook Children's Medical Center Recruiting
Fort Worth, Texas, United States, 76104
Principal Investigator: Paul Thornton, MD         
Sponsors and Collaborators
Cook Children's Health Care System
Investigators
Principal Investigator: Paul Thornton, MD Cook Children's Health Care System
  More Information

Additional Information:
Publications:
Stanley CA, Thornton PS, Finegold DN, Sperling MA: Hypoglycemia in neonates and infants. In Sperling MA ed. Pediatric Endocrinology 2nd edition chpt 7 pages 135-59. 2002.

Responsible Party: Cook Children's Health Care System
ClinicalTrials.gov Identifier: NCT02021604     History of Changes
Other Study ID Numbers: 2012-060
Study First Received: December 20, 2013
Last Updated: July 21, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Cook Children's Health Care System:
Congenital Hyperinsulinism
HI
Hypoglycemia

Additional relevant MeSH terms:
Hyperinsulinism
Congenital Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Pancreatic Diseases
Digestive System Diseases
Infant, Newborn, Diseases
Hypoglycemia
Dihydroxyphenylalanine
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 28, 2014