Utility of 18FDOPA PET/MRI for Focal Hyperinsulinism (18FDOPA HI)

Use of18F-DOPA PET/MRI for the Detection and Localization of Focal Forms of Hyperinsulinism

The purpose of the study is to provide access to 18F-DOPA PET to patients at Washington University and assess the utility of 18F-DOPA PET/MRI as a preoperative tool to detect and localize focal lesions in the pancreas that are causing hyperinsulinism.

Study Overview

• Status: Recruiting
• Conditions: Hyperinsulinism
• Intervention / Treatment: Drug: 18F-Fluoro Dopa PET/MRI Imaging

Detailed Description

Congenital hyperinsulinism (CHI) is a clinically and genetically heterogeneous disorder that is the most common cause of permanent hypoglycemia in infants and children. More than 50% of the medically-unresponsive patients have focal disease. Which is characterized by a distinct region of Beta-cell hyperplasia in the pancreas, due to a somatic loss of a gene that regulates cell proliferation. Resection of the involved region cures most cases of focal HI. Therefore, preoperative identification and localization of focal HI lesions is useful for diagnostic confirmation and surgical guidance of patients with HI that fail pharmacological therapy and are being considered for surgery.

Insulinomas are benign insulin secreting neuroendocrine neoplasms located in the pancreas. They are the most common cause of endogenous hyperinsulinemic hypoglycemia in adults. Approximately 90% are solitary, benign and < 2cm in diameter and therefore represent a challenge to localize. The small size of insulinomas makes detection by conventional imaging techniques such as contrast-enhanced CT (ceCT) and contrast-enhanced MRI challenging. As surgery appears to be the only available treatment option, it remains very critical to localize the tumor to facilitate pancreas preserving surgery. Endoscopic ultrasound is well established in the detection of insulinomas. However, this technique is operator dependent, invasive, and the visualization of the pancreas tail is not always possible. Therefore better imaging techniques to detect these lesions are needed for surgical planning.

Though not FDA approved, noninvasive imaging with 18F-fluoro-L-DOPA (FDOPA) is considered an integral part of standards of care management to identify focal lesions in CHI and potentially insulinomas. This is based on the fact that 18F-DOPA is selectively taken up by neuroendocrine cells, and thus, in focal HI, dense collections of endocrine cells can be visualized by an experienced radiologist. This study aims to determine if using combined positron emission tomography and magnetic resonance imaging will better localize the lesions and help the investigators determine which areas of the pancreas are affected, and assist with the surgical plan.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kathleen J Wharton, BSN, RN; Phone Number: 314-747-1368; Email: kseibel@wustl.edu

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University
      • Contact: Ana M Arbelaez, MD; Phone Number: 314-454-6051; Email: aarbelaez@wustl.edu
      • Sub-Investigator: Maria R Ponisio, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients with confirmed hyperinsulinemic hypoglycemia, diagnosed by elevated insulin levels during hypoglycemia and/or response to glucagon stimulation.
2. Subjects who failed pharmacological therapy with diazoxide or octreotide.
3. Subjects with signed informed consent by themselves or their parents or legal guardians.
4. 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.

Exclusion Criteria:

1. Any other major illness or condition that in the investigator's judgment will substantially increase the risk associated with the subject's participation in this study.
2. Patient must not have any contraindication to MRI as evaluated by a standardized MRI safety questionnaire. If MRI is contraindicated, and patient meets inclusion criteria and has no other contraindications study will be conducted in PET/CT scanner.
3. Cases in which surgery will not be considered by parents or guardians.

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-Fluoro Dopa Imaging; single arm

Drug: 18F-Fluoro Dopa PET/MRI Imaging; The purpose of this research study is to provide access to an imaging study of the pancreas that uses 6-[18F]-Fluoro-L-3,4,-dihydroxyphenylalanine (18F-DOPA)positron emission tomography (PET) and assess the accuracy of this 18F-DOPA-PET/MRI test on distinguishing what part of the pancreas is affected in patients with Hyperinsulinism.; Other Names: 18F-DOPA; 6-[18F]-Fluoro-L-3,4,-dihydroxyphenylalanine; [18F]-Fluorodopa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Increase Access to 18F-DOPA PET/MRI (or PET/CT) for patients with HI who failed medical therapy	To provide access to 18F-DOPA PET/MRI (or PET/CT) for patients with HI who do not respond to pharmacological therapy and are being considered for pancreatic surgery. We will measure this by totaling the number of scans performed yearly.	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accuracy of 18FDOPA PET/MRI to identify focal forms of hyperinsulinism that may be cured by surgery	To identify if data from 18FDOPA PET/MRI imaging can accurately diagnose focal forms of HI when compared to the gold-standard of histopathological findings obtained at surgery in subjects who received a partial or complete pancreatectomy. Currently this type of isotope is not available for diagnosis, of insulinomas.	one year

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: St. Louis Children's Hospital
• Investigators: Principal Investigator: Ana Maria Arbelaez, MD, MSCI, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2020
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: June 18, 2021
• First Submitted That Met QC Criteria: October 8, 2021
• First Posted (Actual): October 22, 2021

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 24, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: hypoglycemia; Infant, Newborn, Diseases; Glucose Metabolism Disorders; Hyperinsulinism; Insulinoma
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dopamine Agents; Dihydroxyphenylalanine
• Other Study ID Numbers: 201801029

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will share de-identified data with researchers at other institutions in a HIPPA compliant format.
• IPD Sharing Time Frame: Data will be available upon request.
• IPD Sharing Access Criteria: PET Imaging data may be shared with other investigators in a HIPPA compliant manor for potential collaboration.
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No