Role of ET-1, Physical Activity, and Sedentary Behavior in Microvascular Dysfunction Following GDM

NCT06547619 | Recruiting Early Phase 1 FDA Drug

• 1 other identifier: 202405270
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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 role of endothelin-1, a potent vasoconstrictor, in aberrant microvascular function in otherwise healthy women with a history of GDM and to identify whether this mechanism is influenced by physical activity and sedentary behavior.

Conditions

Gestational Diabetes; Endothelial Dysfunction; Physical Inactivity

Outcome Measures

Primary Outcomes (1)

• amount of microvascular insulin-mediated dilation

  cutaneous vascular vasodilator responses to insulin perfusion in lactated Ringer's, BQ 788 and BQ-123, and L-NAME treated microdialysis sites

  at the study visit, an average of 4 hours

Study Arms (4)

local lactated Ringer's perfusion

PLACEBO COMPARATOR

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

Drug: Insulin aspart

local BQ-788 and BQ-123 perfusion

EXPERIMENTAL

local ET-1 inhibitors perfused through the microdialysis fiber to serve as the experimental treatment

Drug: Insulin aspart

local L-NAME perfusion

EXPERIMENTAL

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

Drug: Insulin aspart

local BQ-788 + BQ-123 + L-NAME perfusion

EXPERIMENTAL

local ET-1 inhibitors and L-NAME are perfused through the microdialysis fiber to inhibit nitric oxide synthase during the experimental treatment

Drug: Insulin aspart

Interventions

Insulin aspart DRUG

insulin aspart is perfused at 5 ascending concentrations (10\^-8M - 10\^-4 M) for 10 minutes each

local BQ-788 + BQ-123 + L-NAME perfusion; local BQ-788 and BQ-123 perfusion; local L-NAME perfusion; local lactated Ringer's perfusion

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• history of pregnancy within 5 years of the study visit
• had healthy pregnancy OR had gestational diabetes diagnosed by their obstetrician and confirmed according to the American College of Obstetricians and Gynecologists criteria for gestational diabetes.

You may not qualify if:

• skin diseases,
• current tobacco or electronic cigarette/vape pen use,
• diagnosed or suspected hepatic or metabolic disease including diabetes,
• statin or other cholesterol-lowering medication,
• current antihypertensive medication,
• history of preeclampsia or gestational hypertension
• current hypertension,
• current pregnancy,
• body mass index \<18.5 kg/m2,
• allergy to materials used during the experiment.(e.g. latex), known allergies to study drugs.

Sponsors & Collaborators

• Anna Stanhewicz, PhD: lead

Study Sites (1)

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

MeSH Terms

Conditions

Diabetes, Gestational; Sedentary Behavior

Interventions

Insulin Aspart

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Behavior

Intervention Hierarchy (Ancestors)

Insulin, Short-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Central Study Contacts

Anna Reid-Stanhewicz, PHD

CONTACT

319-467-1732; anna-stanhewicz@uiowa.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 7, 2024
• First Posted: August 9, 2024
• Study Start: October 1, 2024
• Primary Completion: May 1, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: December 9, 2025

Record last verified: 2025-12

Locations

US (1)