NADPH Oxidase Role in Gestational Diabetes

Overseen By Anna Reid-Stanhewicz, PHD

Age: 18 - 65

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: Anna Stanhewicz, PhD

Must not be taking: Statins, Antihypertensives

Disqualifiers: Skin diseases, Tobacco use, Diabetes, others

Trial Summary

What is the purpose of this trial?

This trial examines how an enzyme might create harmful molecules that damage blood vessels in healthy women who had diabetes during pregnancy. Researchers use a small, minimally invasive technique to deliver medicine directly to the skin and take cell samples from a vein to study stress markers.

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.

How does the treatment targeting NADPH oxidase differ from other treatments for gestational diabetes?

This treatment is unique because it focuses on reducing oxidative stress by targeting NADPH oxidase, an enzyme that produces reactive oxygen species (ROS) at the fetal-maternal interface. Unlike standard treatments that primarily manage blood sugar levels, this approach aims to address the underlying oxidative stress associated with gestational diabetes. ^{1 2 3 4 5}

Eligibility Criteria

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 am 18 years old or older.

I was diagnosed with gestational diabetes by my doctor.

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.

Trial Timeline

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

Treatment Details

Interventions

• N/A (Other)

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.

Participant Groups

Group I: local apocynin perfusion Experimental Treatment 2 Interventions

local apocynin is perfused through the microdialysis fiber to serve as the NADPH oxidase inhibited experimental treatment

Group II: local apocynin + L-NAME perfusion Experimental Treatment 2 Interventions

local apocynin and L-NAME are perfused through the microdialysis fiber for dual inhibition of NADPH oxidase and nitric oxide synthase

Group III: local L-NAME perfusion Experimental Treatment 2 Interventions

local L-NAME is perfused through the microdialysis fiber to inhibit nitric oxide synthase

Group IV: local lactated Ringer's perfusion Placebo Group 2 Interventions

lactated Ringer's is perfused through the microdialysis fiber to serve as the vehicle control

Who Is Running the Clinical Trial?

Anna Stanhewicz, PhD

Lead Sponsor

Trials

12

Recruited

460+

Findings from Research

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

In a study of 719 patients with gestational diabetes mellitus (GDM) and 1205 control women, the MPO G-463A genetic variant was found to significantly increase the risk of GDM, with the A allele being more frequent in patients than in controls.

The study also revealed that the MPO G-463A variant is associated with higher triglyceride levels and that the CYBA C242T variant correlates with increased pre-pregnancy BMI and oxidative stress, suggesting a link between these genetic factors and metabolic issues related to GDM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myeloperoxidase G-463A and CYBA C242T genetic variants in gestational diabetes mellitus. Jiang, C., Zhou, M., Bai, H., et al.[2023]

In pregnant women with gestational diabetes mellitus (GDM), there is significant oxidative stress indicated by impaired antioxidant defenses and increased free radical production, particularly through the activation of xanthine oxidase.

The study highlights a correlation between the oxidant/antioxidant status in maternal and cord plasma and placental tissue, suggesting that poor glycemic control in GDM may lead to increased oxidative stress affecting both the mother and fetus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxidant status in maternal and cord plasma and placental tissue in gestational diabetes. Biri, A., Onan, A., Devrim, E., et al.[2007]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human placental NAD(P)H oxidase: solubilization and properties. Manes, C.[2017]

References

1. Singapore pubmed.ncbi.nlm.nih.gov

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. [2022]

2. Ireland pubmed.ncbi.nlm.nih.gov

Increased placental expressions of nuclear factor erythroid 2-related factor 2 and antioxidant enzymes in gestational diabetes: Protective mechanisms against the placental oxidative stress? [2019]

3. England pubmed.ncbi.nlm.nih.gov

Myeloperoxidase G-463A and CYBA C242T genetic variants in gestational diabetes mellitus. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Oxidant status in maternal and cord plasma and placental tissue in gestational diabetes. [2007]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Human placental NAD(P)H oxidase: solubilization and properties. [2017]