Metformin for the Treatment of Microvascular Dysfunction After Gestational Diabetes

Gestational Diabetes Clinical Trial

Official title:

Metformin for the Treatment of Microvascular Dysfunction After Gestational Diabetes

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05917587
• Other study ID #: 202303345
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: June 2024
• Est. completion date: July 2029

Study information

• Verified date: April 2024
• Source: University of Iowa
• Contact: Anna Stanhewicz, PhD
• Phone: 3194671732
• Email: anna-stanhewicz[@]uiowa.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this investigation is to examine the mechanisms mediating vascular dysfunction in women who have had gestational diabetes and how metformin may be a valuable treatment tool to improve microvascular function in these women before the onset of disease.

Description:

Women with a history of gestational diabetes mellitus (GDM) are at a 2-fold greater risk for the development of overt cardiovascular disease (CVD) following the effected pregnancy. While subsequent development of type II diabetes elevates this risk, prior GDM is an independent risk factor for CVD morbidity, particularly within the first decade postpartum. GDM is associated with impaired endothelial function during pregnancy and decrements in macro- and microvascular function persist postpartum, despite the remission of insulin resistance following delivery. Collectively, while the association between GDM and elevated lifetime CVD risk is clear, and available evidence demonstrates a link between GDM and vascular dysfunction in the decade following pregnancy, the mechanisms mediating this persistent dysfunction remain unexamined.

The purpose of this investigation is to examine the mechanisms mediating vascular dysfunction in women who have had gestational diabetes and how metformin may be a valuable treatment tool to improve microvascular function in these women before the onset of disease. This study will give rise to a new line of research that will center around the goal of improving lifetime cardiovascular outcomes in women with a history of GDM.

In this study, the investigators use the blood vessels in the skin as a representative vascular bed for examining mechanisms of microvascular dysfunction in humans. Using a minimally invasive technique (intradermal microdialysis for the local delivery of pharmaceutical agents) they examine the blood vessels in a dime-sized area of the skin in women who have had GDM. Local heating of the skin at the microdialysis sites is used to explore differences in mechanisms governing microvascular control. As a compliment to these measurements, the investigators also draw blood from the subjects and isolate the inflammatory cells.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: July 2029
• Est. primary completion date: July 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• =12 weeks and =5 years postpartum

• history of GDM or healthy pregnancy

Exclusion Criteria:

• prediabetes or diabetes (HbA1c =5.7%)

• current tobacco use

• cardiovascular or metabolic disease

• cardiovascular or metabolic medication

• history of hypertension during pregnancy

• current pregnancy

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes, Gestational
• Gestational Diabetes

Intervention

Drug:
• Metformin Hydrochloride
12 weeks: 850mg metformin once daily for first 7 days then twice daily for the remaining 11 weeks.

Other:
• placebo
12 weeks: placebo tablet once daily for the first 7 days then twice daily for the remaining 11 weeks.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Anna Stanhewicz, PhD

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	blood flow response to acetylcholine	cutaneous microvascular dilation (cutaneous conductance ; %max) response to acetylcholine	baseline
Primary	blood flow response to acetylcholine	cutaneous microvascular dilation (cutaneous conductance ; %max) response to acetylcholine	1 week of treatment
Primary	blood flow response to acetylcholine	cutaneous microvascular dilation (cutaneous conductance ; %max) response to acetylcholine	6 weeks of treatment
Primary	blood flow response to acetylcholine	cutaneous microvascular dilation (cutaneous conductance ; %max) response to acetylcholine	12 weeks of treatment
Primary	blood flow response to insulin	cutaneous microvascular dilation (cutaneous conductance ; %max) response to insulin	baseline
Primary	blood flow response to insulin	cutaneous microvascular dilation (cutaneous conductance ; %max) response to insulin	1 week of treatment
Primary	blood flow response to insulin	cutaneous microvascular dilation (cutaneous conductance ; %max) response to insulin	6 weeks of treatment
Primary	blood flow response to insulin	cutaneous microvascular dilation (cutaneous conductance ; %max) response to insulin	12 weeks of treatment
Secondary	Percentage of nitric oxide-dependent dilation	NO-dependent (%) cutaneous microvascular dilation response to acetylcholine	baseline
Secondary	Percentage nitric oxide-dependent dilation	NO-dependent (%) cutaneous microvascular dilation response to acetylcholine	1 week of treatment
Secondary	Percentage of nitric oxide-dependent dilation	NO-dependent (%) cutaneous microvascular dilation response to acetylcholine	6 weeks of treatment
Secondary	Percentage of nitric oxide-dependent dilation	NO-dependent (%) cutaneous microvascular dilation response to acetylcholine	12 weeks of treatment