40 Participants Needed

NADPH Oxidase Role in Gestational Diabetes

AR
Overseen ByAnna Reid-Stanhewicz, PHD
Age: 18 - 65
Sex: Female
Trial Phase: Phase < 1
Sponsor: Anna Stanhewicz, PhD

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the enzyme NADPH oxidase affects blood vessel function in women who have experienced gestational diabetes. It tests various treatments to determine their impact on the production of reactive oxygen species, which can influence blood flow. The trial includes several groups: some receive experimental treatments like apocynin (an enzyme inhibitor) and L-NAME (a nitric oxide synthase inhibitor), while others receive a placebo. Women diagnosed with gestational diabetes by their doctor and who were pregnant within the last five years might be suitable candidates. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants a chance to contribute to groundbreaking medical insights.

Will I have to stop taking my current medications?

If you are currently taking statins, other cholesterol-lowering medications, or antihypertensive medications, you will need to stop, as these are part of the exclusion criteria for the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that apocynin and L-NAME have been studied in various settings, yielding interesting results. Apocynin helps reduce oxidative stress, an imbalance between harmful free radicals and protective antioxidants in the body. In studies with diabetic rats, it lowered blood sugar levels and improved insulin use, suggesting potential benefits for people with blood sugar issues.

L-NAME blocks an enzyme called nitric oxide synthase, which plays a role in various body functions. However, these findings primarily come from animal studies, so effects in humans may differ.

Specific safety information for these treatments in humans is not yet available. As this trial is in its early phase, researchers are still collecting safety data. Early-phase trials are the first step in testing new treatments on people and are crucial for understanding safety. Consider this if you are thinking about participating.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores the roles of NADPH oxidase and nitric oxide synthase in gestational diabetes. Unlike traditional treatments that might focus on managing blood sugar levels through medication or insulin, this trial investigates how inhibiting these enzymes can potentially address underlying causes of the condition. By using local perfusion methods with apocynin and L-NAME, researchers aim to directly target and inhibit these enzymes, offering a novel approach that could lead to more effective interventions in managing gestational diabetes. This study could pave the way for treatments that not only manage symptoms but also tackle the root of the problem.

What evidence suggests that this trial's treatments could be effective for gestational diabetes?

Research has shown that a protein called NADPH oxidase creates harmful molecules known as reactive oxygen species, which can cause problems in diabetes, including gestational diabetes mellitus (GDM). In this trial, participants may receive local apocynin perfusion, which blocks NADPH oxidase and has shown promise in animal studies for reducing this harm. For example, diabetic rats treated with apocynin had lower levels of harmful molecules linked to diabetes complications. Another treatment option in this trial is local L-NAME perfusion, which affects blood vessel function and may help with issues in GDM. Although limited information exists from human studies, these treatments might help with GDM by reducing harmful molecules and improving blood vessel health.46789

Are You a Good Fit for This Trial?

This trial is for women over 18 who had gestational diabetes within the last 5 years and are not currently pregnant. They mustn't have a history of certain conditions like preeclampsia, skin diseases, or metabolic disorders including current diabetes, and can't be on specific medications like statins or antihypertensives.

Inclusion Criteria

You have been pregnant within 5 years of the study visit.
I was diagnosed with gestational diabetes by my doctor.
You have never had gestational diabetes during pregnancy.

Exclusion Criteria

You have had a condition called preeclampsia or high blood pressure during pregnancy.
I have been diagnosed with or suspected to have liver disease or diabetes.
I am taking medication to lower my cholesterol.
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Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Study Visit

Participants undergo intradermal microdialysis and endothelial cell collection to examine microvascular function and NADPH oxidase expression

1 day
1 visit (in-person)

Follow-up

Participants are monitored for any adverse effects following the study visit

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • N/A
Trial Overview The study is looking at how NADPH oxidase might cause poor blood vessel function in healthy women with past gestational diabetes by using substances like Acetylcholine and Insulin aspart to test vascular response.
How Is the Trial Designed?
4Treatment groups
Experimental Treatment
Placebo Group
Group I: local apocynin perfusionExperimental Treatment2 Interventions
Group II: local apocynin + L-NAME perfusionExperimental Treatment2 Interventions
Group III: local L-NAME perfusionExperimental Treatment2 Interventions
Group IV: local lactated Ringer's perfusionPlacebo Group2 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

Anna Stanhewicz, PhD

Lead Sponsor

Trials
12
Recruited
460+

Published Research Related to This Trial

In a study of 80 pregnant women (40 with gestational diabetes and 40 healthy), it was found that those with gestational diabetes had higher levels of the protective protein Nrf2 and antioxidant enzymes like catalase and SOD1 in their placentas, suggesting a response to increased oxidative stress.
The study also revealed that oxidative stress markers were elevated in gestational diabetes patients, with lower total antioxidant status, indicating that while the placenta attempts to protect itself through increased Nrf2 expression, oxidative stress remains a significant concern for both the mother and fetus.
Increased placental expressions of nuclear factor erythroid 2-related factor 2 and antioxidant enzymes in gestational diabetes: Protective mechanisms against the placental oxidative stress?Manoharan, B., Bobby, Z., Dorairajan, G., et al.[2019]
The NAD(P)H oxidase in the syncytiotrophoblast of the human placenta has been successfully solubilized and characterized, revealing it consists of a 58 kDa and a 33 kDa subunit, which distinguishes it from similar enzymes in immune cells.
This enzyme is constitutively active in the trophoblast and generates reactive oxygen species (ROS) at the fetal-maternal interface, suggesting a role in placental function and possibly fetal development.
Human placental NAD(P)H oxidase: solubilization and properties.Manes, C.[2017]
In pregnant women with gestational diabetes mellitus (GDM), serum lipid peroxidation (LPO) levels were significantly higher and glutathione peroxidase 4 (GPx4) levels were significantly lower compared to normal subjects, indicating a potential imbalance in oxidative stress and antioxidant defense during pregnancy.
The study found that higher LPO concentrations were associated with an increased risk of metabolic abnormalities, such as elevated blood pressure and triglycerides, suggesting that LPO could serve as a predictor for metabolic issues in women with GDM.
Association of serum lipid peroxidation and glutathione peroxidase 4 levels with clinical outcomes and metabolic abnormalities among patients with gestational diabetes mellitus: a case-control study in the Chinese population.Zhang, B., Zhang, T., Hu, S., et al.[2022]

Citations

Effects of Apocynin on Heart Muscle Oxidative Stress of Rats ...In the diabetic rats treated with apocynin (233.49 ± 13.29 g), a reduction in bodyweight was observed compared to the control group of 26%. However, there were ...
Apocynin inhibits placental TLR4/NF-κB signaling pathway ...Apocynin dose-dependently decreased systolic blood pressure and proteinuria during gestation. Survival rate of the pups and placental weight were improved by ...
Gestational Diabetes Mellitus: The Crosslink among ...Gestational diabetes mellitus (GDM) is characterized by a set of metabolic complications arising from adaptive failures to the pregnancy period.
Behenic acid alleviates inflammation and insulin resistance ...Here, we demonstrated that daily administration of 10 mg/mL BA during pregnancy effectively ameliorated abnormal glucose metabolism in GDM mice ...
Evaluation of Oxidative Stress and Proinflammatory ...The objective of this study is to estimate proinflammatory cytokines TNF-α, IL-6, IL-8 and antioxidants such as GTX, SOD, uric acid, and bilirubin in GDM and ...
Gestational Diabetes Mellitus: The Crosslink among ...Researchers have identified that inflammation, oxidative stress, and the gut microbiota participate in the development of the disease, with potentially harmful ...
Effects of Apocynin on Heart Muscle Oxidative Stress ...Treatment significantly decreased blood glucose levels and insulin resistance in diabetic rats. In cardiac tissue, ROS levels were higher, and catalase enzyme ...
NLRP3 Inhibitor Tranilast Attenuates Gestational Diabetes ...Tranilast significantly ameliorated GDM symptoms, including maternal body weight, hyperglycemia, insulin insufficiency, glucose intolerance and insulin ...
The application of procyanidins in diabetes and its ...Studies suggest that PCs can lower blood glucose, improve insulin resistance, regulate insulin secretion, protect pancreatic β-cells in diabetic patients, and ...
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