Diazoxide for Hyperinsulinemia

(DzST Trial)

Overseen By Ishwari Nagnur

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Columbia University

Must not be taking: Antidiabetics, Antipsychotics, Corticosteroids, others

Disqualifiers: Diabetes, Cardiovascular diseases, Liver disease, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 1 week

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how insulin, the hormone that lowers blood sugar, functions in the body. Researchers are testing diazoxide, a drug that reduces insulin production, to observe its effects on blood sugar levels in individuals with high insulin levels and obesity. Participants will take the medication for four days, with daily checks of their blood sugar and insulin levels. The trial seeks individuals diagnosed with high insulin levels and a body mass index (BMI) between 30 and 45, indicating obesity. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to contribute to groundbreaking research.

Do I need to stop my current medications to join the trial?

The trial requires that you stop using most antidiabetic medications 30 days before screening, except for metformin, which is allowed. If you are taking other medications for conditions listed in the exclusion criteria, you may need to stop those as well. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that diazoxide is likely to be safe for humans?

Research shows that diazoxide, the treatment under study, has managed low blood sugar levels caused by various conditions. Although it has been used in people before, awareness of the side effects is important. Studies have found common side effects include increased hair growth in 45% of users, fluid retention in 20%, stomach issues in 13%, swelling in 11%, and a low white blood cell count in 9%. These side effects are important to consider when deciding to join a trial involving diazoxide. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for hyperinsulinemia, which often include medications like diazoxide in pill form or surgical interventions, this investigational treatment offers a unique delivery method. Diazoxide oral suspension is administered at a specific dosage of 3 mg/kg per dose over four days, which might provide a more precise and controlled approach to managing insulin levels. Researchers are excited about this treatment because it could offer faster results, potentially reducing insulin levels in just a few days compared to the longer timelines typically associated with other options. This rapid effectiveness, combined with the convenience of an oral suspension, makes it an intriguing alternative for managing hyperinsulinemia.

What evidence suggests that diazoxide might be an effective treatment for hyperinsulinemia?

Research has shown that diazoxide, which participants in this trial will receive, can help treat conditions caused by high insulin levels. About 71% of patients in studies responded well to diazoxide. This medicine reduces the amount of insulin the pancreas produces, helping to control blood sugar levels. It is often used for conditions like hyperinsulinism, where the body produces too much insulin. While not everyone may benefit, diazoxide has shown promise in managing insulin-related problems. ^{2 3 6 7 8}

Who Is on the Research Team?

Joshua R Cook, MD, PhD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for individuals with obesity and high insulin levels, known as hyperinsulinemia. It's designed to understand how the body uses insulin to control blood sugar. Participants will be given diazoxide, which affects insulin production.

Inclusion Criteria

Written informed consent (in English or Spanish) and any locally required authorization (e.g., Health Insurance Portability and Accountability Act) obtained from the participant prior to performing any protocol-related procedures, including screening evaluations.

My BMI is between 30 and 45.

I can understand English or Spanish, both written and spoken.

Exclusion Criteria

Abnormal resting heart rate: < 60 or ≥ 110 bpm

I can provide informed consent in English or Spanish.

Known allergy/hypersensitivity to any component of the medicinal product formulations (including sulfa drugs) or ongoing clinically important allergy/hypersensitivity as judged by the investigator

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive diazoxide oral suspension at 3 mg/kg per dose for 4 days, with fasting glucose and insulin levels checked daily

1 week

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Diazoxide

Trial Overview

The study tests diazoxide at a dose of 2 mg/kg, administered in eight doses. The focus is on how this drug influences the pancreas and its ability to produce insulin, thereby affecting blood sugar regulation in obese individuals with high insulin levels.

How Is the Trial Designed?

Group I: Diazoxide Experimental Treatment 1 Intervention

Subjects will take diazoxide oral suspension at 3 mg/kg per dose for 4 days (total of 8 doses)

Diazoxide is already approved in United States for the following indications:

Approved in United States as Proglycem for:

• Hypoglycemia

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

University of Pisa

Collaborator

Trials

153

Recruited

84,700+

Published Research Related to This Trial

In a study of 295 infants and children treated with diazoxide for hyperinsulinism, 2.4% developed pulmonary hypertension, particularly in those with underlying risk factors like respiratory failure and structural heart disease.

The study also found a notable prevalence of other adverse events, including neutropenia (15.6%), thrombocytopenia (4.7%), and hyperuricemia (5.0%), highlighting the importance of proactive screening for these side effects in patients receiving diazoxide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of Adverse Events in Children With Congenital Hyperinsulinism Treated With Diazoxide. Herrera, A., Vajravelu, ME., Givler, S., et al.[2019]

Diazoxide is an effective treatment for stress-related hyperinsulinism in premature infants, but in this case, it led to severe side effects including cardiorespiratory failure and worsening liver function after 7 weeks of treatment.

The infant's low albumin levels may have increased the toxicity of diazoxide, suggesting that monitoring liver function and albumin levels is crucial when administering this medication, as it is highly protein-bound.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver injury may increase the risk of diazoxide toxicity: a case report. Tas, E., Mahmood, B., Garibaldi, L., et al.[2018]

In patients with insulinoma, diazoxide treatment significantly reduced serum insulin levels and improved tissue sensitivity to insulin after just three days of administration.

Before treatment, insulinoma patients showed lower metabolic clearance rates of insulin compared to controls, indicating that diazoxide effectively enhances insulin metabolism in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of euglycaemic clamping in evaluation of diazoxide treatment of insulinoma. Skrha, J., Svacina, S., Srámková, J., et al.[2019]

In a study of 194 patients with hyperinsulinism, 85.1% were treated with diazoxide, which is the only FDA-approved medication for this condition, and the overall rate of serious adverse events (SAEs) was found to be 9.7%.

Patients with perinatal stress hyperinsulinism experienced a significantly higher rate of SAEs (16.7%) compared to those with genetic forms of hyperinsulinism (3.6%), indicating that caution is needed when prescribing diazoxide to this specific group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rate of Serious Adverse Events Associated with Diazoxide Treatment of Patients with Hyperinsulinism. Thornton, P., Truong, L., Reynolds, C., et al.[2019]

A case study reports successful long-term treatment of persistent hyperinsulinemic hypoglycemia in an infant using diazoxide for 4.5 years, maintaining normal blood sugar levels.

Remarkably, the treatment did not result in any side effects, including the commonly associated hypertrichosis, suggesting a favorable safety profile in this instance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term diazoxide treatment in persistent hyperinsulinemic hypoglycemia of infancy: a patient report. Darendeliler, F., Bundak, R., Bas, F., et al.[2019]

Diazoxide was used to treat two children experiencing hypoglycemia due to hyperinsulinemia, but it resulted in serious side effects including cardiac failure and truncal ataxia.

The adverse effects observed highlight the potential risks associated with diazoxide treatment in pediatric patients, suggesting a need for careful monitoring and consideration of alternative therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications of diazoxide in the treatment of nesidioblastosis. McGraw, ME., Price, DA.[2019]

Diazoxide, a benzothiadiazine, has been shown to effectively manage hypoglycemia in frail patients, particularly those at surgical risk.

This case report highlights the successful treatment of insulinoma with diazoxide, suggesting its potential utility in similar clinical scenarios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case of insulinoma effectively treated with low-dose diazoxide. Yasuda, A., Seki, T., Kitajima, N., et al.[2020]

A 5-year-old girl developed hyperosmolar hyperglycemic syndrome (HHS) with a serum glucose level of 529 mg/dL while being treated with diazoxide and diuretics, highlighting the potential risk of hyperglycemia associated with diazoxide use.

Even at low blood levels of diazoxide (25 µg/dL), it can still lead to hyperglycemia, indicating that patients on diazoxide and diuretics require careful monitoring to prevent complications like HHS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperosmolar hyperglycemic syndrome induced by diazoxide and furosemide in a 5-year-old girl. Nakazawa, H., Naruse, Y., Mori, M., et al.[2021]

Diazoxide is the primary medical treatment for hyperinsulism in neonates, but it can lead to severe adverse effects, as demonstrated in a case of a 43-day-old infant who experienced life-threatening complications including fluid retention, congestive heart failure, and respiratory failure after treatment.

After stopping diazoxide, the infant's condition improved significantly within five days, highlighting the importance of monitoring and managing potential intoxication from this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case of severe diazoxide toxicity. Silvani, P., Camporesi, A., Mandelli, A., et al.[2022]

This study established a population pharmacokinetic model for diazoxide in 22 children with hyperinsulinemic hypoglycemia, showing that the drug's clearance and distribution are proportional to body weight, with females having a 39% higher clearance than males.

A significant finding was that serum diazoxide concentrations exceeding 100 μg/mL were associated with the development of hyperglycemia, highlighting the need for careful monitoring of drug levels to prevent adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Diazoxide in Children with Hyperinsulinemic Hypoglycemia. Kizu, R., Nishimura, K., Sato, R., et al.[2018]

A 21-year-old male with hypoglycemia due to hyperinsulinism did not respond to surgery but showed significant improvement after starting oral Diazoxide, indicating its potential efficacy in managing this condition.

Despite an initial viral pneumonitis and temporary discontinuation of Diazoxide due to hyperglycemia, the patient has been successfully treated with Diazoxide for several years and is now asymptomatic and active, suggesting that Diazoxide can be a viable long-term treatment option when surgery fails.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of hyperinsulinism after partial pancreatectomy: medical or surgical? Schnatz, JD., Siegel, JH.[2013]

Citations

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Among the cohort studies, the pooled estimate of the response rate of diazoxide therapy was 71% (95% CI 50%–93%, Pheterogeneity< 0.001, I2 = 98.3%, Peffect< ...

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jamanetwork.com/journals/jamanetworkopen/fullarticle/2819962

Diazoxide for Severe or Recurrent Neonatal Hypoglycemia

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journals.plos.org/plosone/article?id=10.1371/journal.pone.0246463

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frontiersin.org

frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1628125/full

Real-world experience with the use of diazoxide among ...

In HIGR, 37% of people currently on diazoxide reported experiencing hypoglycemia up to several times per week.

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uptodate.com

uptodate.com/contents/treatment-and-outcomes-of-congenital-hyperinsulinism

Treatment and outcomes of congenital hyperinsulinism

INTRODUCTION. Congenital hyperinsulinism (HI) is the leading cause of persistent hypoglycemia in infants and children.

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accessdata.fda.gov/drugsatfda_docs/label/2024/017453s024lbl.pdf

PROGLYCEM® (diazoxide) oral suspension

Since there are no adequate data on fetal effects of this drug when given to pregnant women, safety in pregnancy has not been established. When the use of ...

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pmc.ncbi.nlm.nih.gov/articles/PMC6073056/

Safety and effectiveness, including intelligence prognosis, ...

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mayoclinic.org

mayoclinic.org/drugs-supplements/diazoxide-oral-route/description/drg-20063406

Diazoxide (oral route) - Side effects & dosage

Diazoxide is used to manage symptoms of hypoglycemia (low blood sugar) that is caused by pancreas cancer, surgery, or other conditions.