Fluorodopa F 18 in Congenital Hyperinsulinism and Insulinoma

NCT02021604 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 2012-060
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

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). Another very similar disease is insulinoma which occurs after birth, but also causes hyperinsulinism. 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.

Conditions

Congenital Hyperinsulinism; Insulinoma

Keywords

Congenital Hyperinsulinism; HI; Hypoglycemia; FDOPA; 18F-DOPA; Hyperinsulinism; Insulinoma

Outcome Measures

Primary Outcomes (2)

• Radioactivity of 18F-DOPA following transport

  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

  1 day

• Accuracy of PET imaging compared to intraoperative pancreatic biopsy in patients with congenital hyperinsulinism

  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

  up to one month

Secondary Outcomes (2)

• Accuracy of PET imaging compared to intraoperative pancreatic biopsy in patients with insulinoma

  up to one month

• Ratio of Standard Uptake Value max to sub max

  up to one month

Study Arms (1)

Pancreatic Imaging with Fluorodopa F 18

EXPERIMENTAL

Drug: Fluorodopa F 18

Interventions

Fluorodopa F 18 DRUG

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.

Also known as: Fluorodopa 18F (International Non-Proprietary Name), 6-[18F]fluorolevodopa (U.S. Pharmacopeia), Fluorodopa F 18 (CAS Number 75290-51-6)

Pancreatic Imaging with Fluorodopa F 18

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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 or insulinoma based on clinical evaluation 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Cook Children's Health Care System: lead

Study Sites (1)

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

RECRUITING

Related Publications (9)

• de Lonlay-Debeney P, Poggi-Travert F, Fournet JC, Sempoux C, Dionisi Vici C, Brunelle F, Touati G, Rahier J, Junien C, Nihoul-Fekete C, Robert JJ, Saudubray JM. Clinical features of 52 neonates with hyperinsulinism. N Engl J Med. 1999 Apr 15;340(15):1169-75. doi: 10.1056/NEJM199904153401505.

  PMID: 10202168 BACKGROUND

• Thornton PS, Finegold DN, Stanley CA, Sperling MA. Hypoglycemia in the infant and child. In Sperling MA ed. Pediatric Endocrinology 2nd ed., pp 367-84. Philadelphia: Saunders, 2002.

  BACKGROUND

• 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.

  BACKGROUND

• Suchi M, Thornton PS, Adzick NS, MacMullen C, Ganguly A, Stanley CA, Ruchelli ED. Congenital hyperinsulinism: intraoperative biopsy interpretation can direct the extent of pancreatectomy. Am J Surg Pathol. 2004 Oct;28(10):1326-35. doi: 10.1097/01.pas.0000138000.61897.32.

  PMID: 15371948 BACKGROUND

• Jager PL, Chirakal R, Marriott CJ, Brouwers AH, Koopmans KP, Gulenchyn KY. 6-L-18F-fluorodihydroxyphenylalanine PET in neuroendocrine tumors: basic aspects and emerging clinical applications. J Nucl Med. 2008 Apr;49(4):573-86. doi: 10.2967/jnumed.107.045708. Epub 2008 Mar 14.

  PMID: 18344441 BACKGROUND

• Otonkoski T, Nanto-Salonen K, Seppanen M, Veijola R, Huopio H, Hussain K, Tapanainen P, Eskola O, Parkkola R, Ekstrom K, Guiot Y, Rahier J, Laakso M, Rintala R, Nuutila P, Minn H. Noninvasive diagnosis of focal hyperinsulinism of infancy with [18F]-DOPA positron emission tomography. Diabetes. 2006 Jan;55(1):13-8.

  PMID: 16380471 BACKGROUND

• Mohnike K, Blankenstein O, Minn H, Mohnike W, Fuchtner F, Otonkoski T. [18F]-DOPA positron emission tomography for preoperative localization in congenital hyperinsulinism. Horm Res. 2008;70(2):65-72. doi: 10.1159/000137655. Epub 2008 Jun 12.

  PMID: 18547951 BACKGROUND

• 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.

  PMID: 17236890 BACKGROUND

• 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.

  PMID: 17895314 BACKGROUND

Related Links

• Cook Children's Endocrinology

MeSH Terms

Conditions

Congenital Hyperinsulinism; Insulinoma; Hypoglycemia; Hyperinsulinism

Interventions

fluorodopa F 18

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Adenoma, Islet Cell; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Endocrine System Diseases

Study Officials

• Paul Thornton, MD

  Cook Children's Health Care System

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Deborah Rafferty, PhD

CONTACT

682-303-1363; Deborah.Rafferty@cookchildrens.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2013
• First Posted: December 27, 2013
• Study Start: October 9, 2013
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: July 16, 2024

Record last verified: 2024-07

Locations

US (1)