FDOPA/PET Imaging for Congenital Hyperinsulinism

(DOPA PET Trial)

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Miguel Pampaloni

Must be taking: Diazoxide, Octreotide

Must not be taking: Nifedipine, Glucagon

Disqualifiers: Hepatic insufficiency, Renal insufficiency

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

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how well a special imaging method called FDOPA/PET (18F-Fluoro Dopa Imaging) can assist doctors in planning surgery for congenital hyperinsulinism, a condition where the pancreas releases too much insulin. This condition can cause low blood sugar, and the imaging aims to pinpoint problem areas in the pancreas. Participants should have congenital hyperinsulinism with low blood sugar that medication cannot control. This trial is especially for children, often infants, with specific genetic markers related to their condition. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

Yes, you will need to stop taking your current medications in time to have a washout period (time without taking certain medications) before the scheduled PET scan.

What prior data suggests that FDOPA/PET imaging is safe for pre-operative diagnostics?

Research has shown that 18F-Fluoro Dopa (F-FDOPA) imaging is safe for humans. Studies indicate that F-FDOPA PET, a type of imaging test, is easy for patients to handle and is commonly used in certain situations. This imaging helps doctors identify specific areas in the pancreas that might require surgery.

In past studies, patients who underwent this imaging test did not report any major side effects, suggesting that the procedure is generally safe for participants. While all medical procedures carry some risk, evidence suggests that F-FDOPA imaging is a dependable and low-risk option for diagnosing conditions like congenital hyperinsulinism. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike standard treatments for congenital hyperinsulinism, which typically involve medications like diazoxide or surgery to remove part of the pancreas, the FDOPA/PET imaging method offers a unique diagnostic approach. This technique uses 18F-Fluoro Dopa, a special imaging agent, to pinpoint the exact areas in the pancreas causing excessive insulin production. Researchers are excited because this precise imaging could lead to more targeted and less invasive treatment options, potentially sparing patients from extensive surgery and its associated risks.

What evidence suggests that FDOPA/PET is effective for congenital hyperinsulinism?

Research has shown that 18F-Fluoro Dopa (FDOPA) imaging, which participants in this trial will undergo, can effectively identify specific problem areas in the pancreas for people with congenital hyperinsulinism (CHI). Studies have demonstrated that FDOPA PET imaging excels at finding and pinpointing these areas, which is crucial for planning surgery. This imaging method is particularly effective at distinguishing between focal (localized) and diffuse (spread out) forms of the condition. Accurate pinpointing helps surgeons focus only on the affected areas, leading to better outcomes. Overall, FDOPA imaging is a promising tool for improving surgical planning in CHI patients. ^{3 4 5 6 7}

Who Is on the Research Team?

Miguel Hernandez Pampaloni, MD, PhD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for anyone, especially infants aged 0-6 months with uncontrolled hypoglycemia due to congenital hyperinsulinism, who have normal liver and kidney function. It's not for those on certain third-line hyperinsulinism medications or with liver/kidney insufficiency.

Inclusion Criteria

Able to withdraw medications in time to wash out prior to the scheduled PET scan

I am an infant aged 0-6 months, the typical age for this condition.

I have uncontrolled low blood sugar after pancreas surgery.

Exclusion Criteria

I am taking third-line medications like nifedipine or glucagon for hyperinsulinism.

I have liver or kidney problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo FDOPA PET/CT imaging to differentiate focal and diffuse forms of congenital hyperinsulinism and locate focal lesions in the pancreas

4 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 18F-Fluoro Dopa Imaging

Trial Overview

The study tests if a special PET scan using FDOPA can tell apart different types of congenital hyperinsulinism and pinpoint lesions in the pancreas before surgery.

How Is the Trial Designed?

Group I: Single Arm, Experimental Treatment 1 Intervention

Patients with clinically diagnosed congenital hyperinsulinism

Who Is Running the Clinical Trial?

Miguel Pampaloni

Lead Sponsor

Trials

2

Recruited

60+

Published Research Related to This Trial

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]

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]

18F-6-fluoro-l-dopa PET/CT is the preferred imaging technique for detecting and localizing focal lesions in infants and children with congenital hyperinsulinism, which causes severe hypoglycemia.

Surgical removal of these focal lesions, guided by PET/CT imaging, can potentially cure the condition with minimal pancreatectomy, reducing the risk of brain damage associated with persistent hypoglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-6-Fluoro-l-Dopa PET/CT Imaging of Congenital Hyperinsulinism. States, LJ., Davis, JC., Hamel, SM., 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]

F-DOPA PET and PET/CT have shown high sensitivity (88%) and specificity (79%) in diagnosing congenital hyperinsulinism (CHI) based on a meta-analysis of 10 studies involving 181 patients.

The accuracy of F-DOPA PET and PET/CT in detecting CHI is supported by a high area under the receiver-operating characteristic curve (0.92), indicating these imaging techniques are reliable diagnostic tools, although clinicians should be aware of potential false-positive and false-negative results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic role of 18F-dihydroxyphenylalanine positron emission tomography in patients with congenital hyperinsulinism: a meta-analysis. Yang, J., Hao, R., Zhu, X.[2016]

In a 55-day-old boy with hypoglycemia, 18F-DOPA PET/CT imaging successfully identified a focal lesion in the pancreas associated with congenital hyperinsulinism.

The imaging also revealed a left thoracic paraspinal neuroblastoma, indicating that 18F-DOPA PET/CT can be effective in detecting multiple conditions in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroblastoma Shown on 18F-DOPA PET/CT Performed to Evaluate Congenital Hyperinsulinism. O'Brien, SR., States, LJ., Zhuang, H.[2023]

In a study of 19 children with congenital hyperinsulinism, 18F-DOPA PET/CT successfully identified focal forms of the disease in 10 participants, allowing for targeted surgical resection in 4 cases, leading to complete recovery.

The imaging technique demonstrated a significant difference in uptake between focal lesions and normal pancreatic tissue, indicating its effectiveness in localizing focal CHI for surgical planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of 18F-DOPA PET/CT in the diagnosis of the congenital focal form of hyperinsulinism in children. Chroustova, D., Trnka, J., Pudlac, A., et al.[2021]

FDOPA PET/CT is the primary imaging method for identifying and localizing focal congenital hyperinsulinism (CHI), but it has limitations such as difficulty in detecting small focal forms and potential misinterpretation due to physiological uptake.

Alternative PET imaging techniques using gallium-68 labeled tracers targeting β cell mass or somatostatin receptors may offer more accessible and effective options for diagnosing CHI, addressing the limitations of FDOPA PET/CT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strengths and limitations of using 18fluorine-fluorodihydroxyphenylalanine PET/CT for congenital hyperinsulinism. Montravers, F., Arnoux, JB., Ribeiro, MJ., et al.[2019]

The (18)F-DOPA-PET-CT scan is effective in distinguishing between diffuse and focal congenital hyperinsulinism (CHI) in infants, with accurate results in 14 out of 19 children studied.

However, the scan was inaccurate in locating or sizing the focal lesions in 36% of cases, indicating that while it is a useful tool, intraoperative histologic confirmation is necessary to ensure complete resection of the lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The predictive value of preoperative fluorine-18-L-3,4-dihydroxyphenylalanine positron emission tomography-computed tomography scans in children with congenital hyperinsulinism of infancy. Zani, A., Nah, SA., Ron, O., 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]

The 18F-DOPA PET examination was highly effective in detecting hyperplastic lesions in patients with congenital hyperinsulinism, identifying focal lesions in 12 out of 14 cases, and accurately locating the lesions in 91.7% of those cases.

Surgical resection of the identified focal hyperplastic lesions in the pancreas was performed safely in all cases under 2 years of age, demonstrating that this approach can be an effective treatment for congenital hyperinsulinism, although intraoperative pathologic examination is recommended to confirm lesion distribution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Congenital hyperinsulinism treated by surgical resection of the hyperplastic lesion which had been preoperatively diagnosed by 18F-DOPA PET examination in Japan: a nationwide survey. Kanamori, Y., Watanabe, T., Yorifuji, T., et al.[2019]

Citations

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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 ...

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jnm.snmjournals.org

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

18F-6-Fluoro-l-Dopa PET/CT Imaging of Congenital ...

An example given for a PET/CT effective dose using a 25-MBq 18F-FDOPA injection was 13.25 mSv, with 18F-FDOPA contributing 7.55 mSv and low-dose ...

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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 ...

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sciencedirect.com

sciencedirect.com/science/article/pii/S0001299824000801

Update on the Role of [ 18 F]FDOPA PET/CT

Results indicate that [18F]FDOPA may be more sensitive for detecting primary PCC (sporadic or related to non-SDHx mutations), whereas [68Ga]SSA PET performs ...

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academic.oup.com

academic.oup.com/jcem/article/93/3/869/2598561

Evaluation of [ 18 F]Fluoro-l-DOPA Positron Emission ...

The integrated [ 18 F]FDOPA PET-CT is accurate to localize the lesion in focal CHI and is a valuable tool to guide the surgeon in limited pancreatic resection.

6.

pmc.ncbi.nlm.nih.gov

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

18F-FDOPA and 68Ga-dotatate PET imaging in congenital ...

F-FDOPA PET has been shown to be the reference imaging tool in CHI and is used nowadays quite successfully jointly with genetic testing in defining the focal ...

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clinicaltrials.gov

clinicaltrials.gov/study/NCT02021604

Fluorodopa F 18 in Congenital Hyperinsulinism and ...

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 ...