The Impact of Gestational Diabetes Mellitus on Cerebral Blood Flow and Cerebrovascular Function After Pregnancy

NCT06911372 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 202410260
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

Gestational Diabetes Mellitus (GDM) currently affects approximately 14% of all pregnancies worldwide. Importantly, the health-related consequences of GDM extend well beyond pregnancy, such that women with a history of GDM have a 40% increased risk of cerebrovascular diseases and a 67% increased risk of dementia, compared to women with a history of uncomplicated pregnancy. Women with a history of GDM have impaired skin microvascular function, compared with women with a history of uncomplicated pregnancy. Therefore, it's likely that GDM results in impaired brain blood vessel function, yet there is little-to-no information regarding the effects of GDM on brain blood vessel health and function after pregnancy. Therefore, the purpose of the study is to evaluate the effects of GDM on brain blood flow and brain blood vessel function in healthy women with either a history of GDM or uncomplicated pregnancy. In this study, the investigators will use two different types of ultrasound to non-invasively measure brain blood flow. Brain blood vessel function will be evaluated by examining the brain blood flow responses to increases in carbon dioxide (the increases in carbon dioxide are similar to what is experienced during a breath hold). Additionally, the investigators will compare the brain blood flow results to skin microvascular function to explore potential mechanisms behind possible impairments in brain blood vessel function. Skin microvascular function will be assessed using a minimally invasive technique (intradermal microdialysis for the local delivery of pharmaceutical agents) on dime sized areas of the forearm. Finally, for screening purposes and to further explore potential mechanisms behind any potential impairments in brain blood vessel function, the investigators will perform blood draws to determine the metabolic health of the participants and to analyze for substances that influence blood vessel function.

Conditions

Gestational Diabetes Mellitus (GDM); Postpartum Women; Uncomplicated Pregnancy

Keywords

Gestational Diabetes; Brain Blood Flow; Pregnancy; Postpartum

Outcome Measures

Primary Outcomes (3)

• Stepped hypercapnia-induced change in middle cerebral artery velocity

  Middle cerebral artery velocity responses to stepped concentrations of inhaled carbon dioxide gas

  During the study visit, an average of 5 hours

• Hypercapnia-induced change in internal carotid artery diameter

  Internal carotid artery shear-mediated dilation response to inhaled carbon dioxide

  During the study visit, an average of 5 hours

• Change in microvascular blood flow response to increasing concentrations of acetylcholine

  Cutaneous vascular vasodilator responses to acetylcholine perfusion in lactated Ringer's, ketorolac, and L-NAME treated microdialysis sites.

  During the study visit, an average of 5 hours

Study Arms (1)

Vascular Tests

EXPERIMENTAL

All women will complete the same protocol, regardless of pregnancy history.

Drug: Intradermal Microdialysis; Other: Brain Blood Flow Tests; Other: Local Heating

Interventions

Intradermal Microdialysis DRUG

A total of three microdialysis sites will be perfused with ringer's solution, L-NAME, or ketorolac (one drug per site). After a baseline period, all three sites will undergo tests of blood vessel function including an acetylcholine dose-response protocol and a test of maximal skin blood flow with sodium nitroprusside.

Vascular Tests

Brain Blood Flow Tests OTHER

Participants will complete CO2 breathing procedures to evaluate brain blood vessel health.

Vascular Tests

Local Heating OTHER

A dime-sized heater will be placed on the skin to evaluate cutaneous microvascular function

Vascular Tests

Eligibility Criteria

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

You may qualify if:

• Post-partum women
• years or older
• Delivered within 5 years from the study visit
• History of gestational diabetes diagnosed by an obstetrician and confirmed according to the American College of Obstetricians and Gynecologists criteria for gestational diabetes OR history of uncomplicated pregnancy (defined as no history of gestational diabetes, hypertensive pregnancy, or other gestational disorder).

You may not qualify if:

• Skin diseases
• Current tobacco use
• Diagnosed or suspected hepatic or metabolic disease including diabetes
• Diagnosed with depression or other mood-related disorders, asthma, chronic obstructive pulmonary disease, cystic fibrosis, or pulmonary fibrosis
• Use of prescribed NSAIDs, statins or other cholesterol-lowering medication, antihypertensive medication, carbonic anhydrase inhibitors, corticosteroids, thyroid medications, antidepressants or mood stabilizers, diuretics, phenothiazines, or benzodiazepines
• History of preeclampsia or gestational hypertension,
• History or family history of panic disorder,
• Currently pregnant
• Body mass index \<18.5 kg/m2,
• Allergy to materials used during the experiment (e.g. latex), known allergies to study drugs.
• History of heavy alcohol use/binge drinking,
• Have planned procedures with radiological contrast,
• Have a major dental procedure/surgery coming up, such as a dental extraction
• Anatomy of the middle cerebral artery or internal carotid artery that prevents adequate ultrasonography and/or and data collection

Sponsors & Collaborators

• Anna Stanhewicz, PhD: lead

Study Sites (1)

Iowa Bioscience Innovation Facility

Iowa City, Iowa, 52242, United States

RECRUITING

MeSH Terms

Conditions

Diabetes, Gestational

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

Central Study Contacts

Anna Reid-Stanhewicz, PHD

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: March 12, 2025
• First Posted: April 4, 2025
• Study Start: August 22, 2025
• Primary Completion (Estimated): April 15, 2027
• Study Completion (Estimated): April 15, 2028
• Last Updated: December 16, 2025

Record last verified: 2025-12

Locations

US (1)