18FDOPA PET/MRI for Hyperinsulinism

(18FDOPA HI Trial)

Recruiting at 1 trial location

Overseen By Kathleen J Wharton, BSN, RN

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Disqualifiers: Major illness, MRI contraindication, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new imaging method called 18F-DOPA PET/MRI to help doctors identify specific problem areas in the pancreas that cause hyperinsulinism, a condition where excessive insulin leads to low blood sugar. The goal is to determine if this imaging can better prepare doctors for surgery. It offers a valuable opportunity for individuals with persistent low blood sugar issues that haven't improved with regular medication and whose doctors recommend surgery. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, allowing participants to contribute to advancements in medical imaging.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It seems likely that you may continue your medications unless advised otherwise by your doctor.

What prior data suggests that 18F-Fluoro Dopa PET/MRI Imaging is safe for detecting hyperinsulinism?

Research has shown that 18F-Fluoro Dopa PET/MRI scans are generally safe. Studies have found that using 18F-DOPA in these scans helps identify and locate areas causing high insulin levels. This imaging method has been safely used for conditions like congenital hyperinsulinism and certain tumors.

In past studies with 18F-DOPA PET/CT scans, most patients did not experience serious side effects. The scan uses a small amount of radioactive material, but it is considered safe for medical purposes. There are no specific reports of major negative effects from those who have undergone this type of scan.

Overall, the available safety data suggests that 18F-Fluoro Dopa PET/MRI is a reliable and safe option for detailed scans related to high insulin levels. However, as with any medical procedure, discussing potential risks and benefits with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using 18F-Fluoro Dopa PET/MRI for hyperinsulinism because it offers a precise way to visualize the pancreas and detect abnormal insulin-producing cells. Unlike traditional imaging methods, this technique uses a special radioactive tracer, 18F-Fluoro Dopa, which highlights areas of excess insulin production with high accuracy. This targeted imaging could lead to better diagnosis and treatment plans, potentially improving outcomes for patients with hyperinsulinism.

What evidence suggests that 18F-Fluoro Dopa PET/MRI Imaging is effective for detecting and localizing focal lesions in hyperinsulinism?

Research has shown that a special scan called 18F-Fluoro Dopa PET/MRI, which participants in this trial will undergo, effectively identifies problem areas in the pancreas for individuals with high insulin levels. A review of studies found that this scan excels at pinpointing exact spots that may require surgery. 18F-DOPA PET is the preferred method for locating these problem areas. This imaging technique allows doctors to see precisely where the issue lies in the pancreas, guiding accurate surgical treatment. Such precise detection can lead to better outcomes for patients with this condition. ^{1 5 6 7 8}

Who Is on the Research Team?

Ana Maria Arbelaez

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for patients with hyperinsulinemic hypoglycemia who can't be managed safely with standard treatments and need surgery. They must have high insulin levels during low blood sugar episodes or respond to glucagon stimulation, have failed therapy with diazoxide or octreotide, and provide informed consent.

Inclusion Criteria

Subjects with signed informed consent by themselves or their parents or legal guardians

I have been diagnosed with low blood sugar due to high insulin levels.

I have tried diazoxide or octreotide for my condition without success.

Exclusion Criteria

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

Surgery is not an option for me as decided by my parents or guardians.

I can safely undergo an MRI, or if not, a PET/CT scan.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo 18F-DOPA PET/MRI imaging to detect and localize focal lesions in the pancreas

1-2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging and potential surgery

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 18F-Fluoro Dopa PET/MRI Imaging

Trial Overview The study tests the use of a special imaging technique called 18F-Fluoro Dopa PET/MRI to find and pinpoint focal lesions in the pancreas causing hyperinsulinism before surgery at Washington University.

How Is the Trial Designed?

Group I: 18F-Fluoro Dopa Imaging Experimental Treatment 1 Intervention

single arm

18F-Fluoro Dopa PET/MRI Imaging is already approved in United States, European Union for the following indications:

Approved in United States as 18F-Fluorodopa PET for:

• Evaluation of adult patients with suspected Parkinsonian syndromes
• Detection and localization of focal lesions in the pancreas causing hyperinsulinism

Approved in European Union as 18F-DOPA PET for:

• Detection of neuroendocrine tumors
• Staging and restaging of carcinoid tumors
• Detection of persistent and residual medullary thyroid cancer

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

St. Louis Children's Hospital

Collaborator

Trials

30

Recruited

83,200+

Published Research Related to This Trial

Gadolinium-based contrast agents (GBCAs) have a strong safety record in MRI imaging, but there are known risks such as acute adverse reactions and nephrogenic systemic fibrosis that require ongoing management and understanding.

The review highlights that certain populations, including those with kidney issues, are at higher risk for complications from GBCAs, and it also discusses the emerging use of ferumoxytol as a non-GBCA alternative with its own risk profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety issues related to intravenous contrast agent use in magnetic resonance imaging. Ponrartana, S., Moore, MM., Chan, SS., et al.[2021]

Two new molecular MRI agents have been approved for clinical use recently, and a third is in advanced clinical trials, indicating progress in the development of safer imaging options.

The review emphasizes the importance of prioritizing safety and efficacy in the design of molecular MRI agents, especially in light of past concerns like nephrogenic systemic fibrosis (NSF), which has seen no new cases reported since safety guidelines were implemented.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular MRI of the Cardiovascular System in the Post-NSF Era. Sosnovik, DE., Caravan, P.[2021]

In a study involving 2,102 adult patients, gadodiamide injection was found to be safe at a dose of 0.1 mmol/kg, with only 4.4% experiencing adverse events, primarily mild discomfort at the injection site.

No severe adverse events or deaths were reported, indicating that gadodiamide is a well-tolerated non-ionic contrast agent for MR imaging of the central nervous system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical evaluation of the tolerability of gadodiamide, a new nonionic contrast agent in MRI of the central nervous system]. Aslanian, V., Lemaignen, H., Bunouf, P., et al.[2014]

The use of (18)F-DOPA PET scans can detect focal forms of congenital hyperinsulinism, but the uptake of (18)F-DOPA does not necessarily indicate the insulin-secreting ability of pancreatic lesions, as shown in a case study of a boy with a mutation in the ABCC8 gene.

The patient experienced spontaneous resolution of hypoglycemia without significant insulin release, suggesting that clinical remission can occur without the death of abnormal β-cells, highlighting a potential functional recovery mechanism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lasting 18F-DOPA PET uptake after clinical remission of the focal form of congenital hyperinsulinism. Yorifuji, T., Hosokawa, Y., Fujimaru, R., et al.[2017]

In a study of 17 Japanese infants with congenital hyperinsulinism, [(18)F]DOPA PET showed limited accuracy in diagnosing the condition, with only 7 out of 17 cases aligning with molecular diagnoses when assessed by simple inspection.

The diagnostic accuracy improved significantly when using a quantitative measure called the 'Pancreas Percentage', leading to consistent results in 10 out of 17 patients, indicating that this method enhances the effectiveness of [(18)F]DOPA PET for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic accuracy of [¹⁸F]-fluoro-L-dihydroxyphenylalanine positron emission tomography scan for persistent congenital hyperinsulinism in Japan. Masue, M., Nishibori, H., Fukuyama, S., et al.[2022]

Congenital hyperinsulinism is a major cause of hypoglycemia in infants, and identifying focal hyperinsulinism can lead to a cure through partial pancreatectomy.

Using FDOPA-PET imaging allows for effective functional mapping of hyperinsulinism by highlighting areas of the pancreas that utilize L-DOPA at higher rates, aiding in the localization of the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluorine-18 DOPA-PET and PET/CT Imaging in Congenital Hyperinsulinism. Houseni, M., Chamroonrat, W., Zhuang, H., et al.[2016]

In a study of 25 preoperative 18F-FDOPA PET/CT scans in patients with insulinoma, the imaging technique successfully localized insulinomas in 84% of cases, demonstrating its effectiveness for diagnosis.

The study found that early imaging after carbidopa premedication improved detection rates, with some lesions only visible in early scans, highlighting the importance of timing in imaging protocols for better diagnostic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early 18F-FDOPA PET/CT imaging after carbidopa premedication as a valuable diagnostic option in patients with insulinoma. Leroy-Freschini, B., Amodru, V., Addeo, P., et al.[2020]

The introduction of 6-(18)F-fluoro-L-dopa ((18)F-FDOPA) PET and PET/CT imaging has enhanced the ability to study neuroendocrine tumors (NETs) and pancreatic beta-cell hyperplasia, providing a valuable tool for diagnosis and management.

Institutions with expertise in treating NETs can significantly benefit from (18)F-FDOPA PET/CT, as it aids in guiding therapy to achieve better tumor control and maximize cytoreduction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-FDOPA: a multiple-target molecule. Minn, H., Kauhanen, S., Seppänen, M., et al.[2016]

In a study involving six patients with hyperinsulinemic hypoglycemia, 18F-FDOPA PET imaging was only positive in one case, indicating its limited effectiveness in detecting insulinomas and beta-cell hyperplasia in adults.

The pancreatic uptake of 18F-FDOPA was not significantly different between patients with hyperinsulinemic hypoglycemia and a control group, suggesting that this imaging technique may not reliably localize insulin-secreting tumors in adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limited value of 18F-F-DOPA PET to localize pancreatic insulin-secreting tumors in adults with hyperinsulinemic hypoglycemia. Tessonnier, L., Sebag, F., Ghander, C., et al.[2019]

In a phase II clinical trial involving 104 patients, ferumoxtran-10 was found to be a safe and well-tolerated contrast agent for magnetic resonance imaging, with only 15% of patients reporting mild adverse events.

The most common side effects included dyspnea (3.8%), chest pain (2.9%), and rash (2.9%), but no serious adverse events occurred, and there were no significant changes in vital signs or laboratory results during the 48-hour observation period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of ultrasmall superparamagnetic iron oxide ferumoxtran-10: phase II clinical trial data. Sharma, R., Saini, S., Ros, PR., et al.[2019]

Gadolinium-based contrast agents have a strong safety record for MRI use, but a serious condition called nephrogenic systemic fibrosis was linked to their use in patients with severe kidney issues, leading to significant changes in medical practices since 2009.

Following the identification of nephrogenic systemic fibrosis, new guidelines were implemented that have nearly eliminated the occurrence of this disease, highlighting the importance of monitoring and adjusting medical practices based on emerging safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Effects of Gadolinium-Based Contrast Agents: Changes in Practice Patterns. Forghani, R.[2022]

In a study of 10 patients with confirmed hyperinsulinemic hypoglycemia, 18F-DOPA PET successfully localized pancreatic lesions in 9 out of 10 cases, which were later confirmed by histological analysis.

18F-DOPA PET demonstrated greater sensitivity than CT or MRI in identifying insulin-secreting tumors and beta-cell hyperplasia, making it a valuable diagnostic tool when other imaging methods yield negative results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluorine-18-L-dihydroxyphenylalanine (18F-DOPA) positron emission tomography as a tool to localize an insulinoma or beta-cell hyperplasia in adult patients. Kauhanen, S., Seppänen, M., Minn, H., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3553406/

The Value of Radiologic Interventions and 18F-DOPA PET ... This systematic review and meta-analysis found evidence for the superiority of 18F-DOPA PET in diagnosing and localizing focal CHI in patients requiring surgery ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05088798

Utility of 18FDOPA PET/MRI for Focal 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 ...

3. jnm.snmjournals.org jnm.snmjournals.org/content/62/supplement_2/51s

18F-6-Fluoro-l-Dopa PET/CT Imaging of Congenital ... F-6-fluoro-l-dopa PET/CT is the method of choice for the detection and localization of a focal lesion of hyperinsulinism. Surgical resection of ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01468454

Phase II Safety and Efficacy Study of 18FDOPA PET-CT in ... 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 ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0001299824000801

Update on the Role of [ 18 F]FDOPA PET/CT 18 F FDOPA is a radiopharmaceutical used in a broad spectrum of diseases, including neuroendocrine tumors (NETs), congenital hyperinsulinism, parkinsonian ...

6. jnm.snmjournals.org jnm.snmjournals.org/content/62/Supplement_2/51S

18F-6-Fluoro-l-Dopa PET/CT Imaging of Congenital ... 18 F-6-fluoro-l-dopa PET/CT is the method of choice for the detection and localization of a focal lesion of hyperinsulinism.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01916148

Study Details | NCT01916148 | 18F-L-Fluoro-DOPA PET ... This purpose of this study is to determine the ability of an 18F-fluoro-L-dihydroxyphenylalanine (18F-DOPA) PET (Positron Emission Tomography) scan to detect a ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8255214/

18F-FDOPA and 68Ga-dotatate PET imaging in congenital ... F-FDOPA as described in the literature is superior but when unavailable 68Ga-DOTATATE may be a reasonable alternative. Keywords: CHI, congenital hyperinsulinism ...