NCT07218653

Sex-Specific Cerebrovascular Dysfunction in Metabolic Syndrome-Role of COX

• Status: Not Yet Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 72 (estimated)
• Sponsor: University of Wisconsin, Madison · Academic / Other
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

Summary

This study tests the hypothesis that Metabolic Syndrome (MetSyn) decreases cerebral blood flow (CBF) more in females than males due in part to the sex-specific loss of COX vasodilation. Male and female participants will be enrolled in two groups: Health Controls versus participants with MetSyn.

Detailed description

The central hypothesis is that MetSyn decreases CBF more in females than males due in part to the sex-specific loss of COX vasodilation. This hypothesis is based on extensive preliminary data demonstrating MetSyn induces: 1) 3-fold larger reductions in CBF in females that abolish sex differences, 2) region-specific CBF reduction patterns, and 3) a greater loss of COX-mediated vasodilation in females. This hypothesis is tested via three Specific Aims: * Aim 1: Determine the extent of sex differences in MetSyn-driven CBF reductions. The investigators hypothesize females with MetSyn will demonstrate larger decrements in global, grey matter and white matter CBF versus males. * Aim 2: Determine the sex-by-region interactions of MetSyn reductions in CBF. The investigators hypothesize females will demonstrate larger regional CBF declines-particularly in regions known to be impacted very early in brain pathologies and/or specifically impaired by insulin resistance. * Aim 3: Determine the role of COX signaling in mediating CBF changes in MetSyn. The investigators hypothesize COX vasodilation is reduced more in females than males with MetSyn. All consented participants will conduct a screening visit with a blood panel to identify control vs MetSyn eligibility. Once eligible, participants complete three laboratory visits (each lasting about 2 hours): 1. Exercise Visit: VO2 Max, DEXA for adiposity quantification, NIH Toolbox to assess neurocognitive function 2. MRI Visit 1: blinded to either Placebo or Indomethacin 3. MRI Visit 2: blinded to either Placebo or Indomethacin

Conditions

• Metabolic Syndrome

Interventions

Type	Name	Description
DRUG	Indomethacin	Indomethacin is a nonsteroidal anti-inflammatory. It prevents the production of prostaglandins, endogenous signaling molecules known to cause symptoms from inflammation. Indomethacin (1.5 mg/kg) will be taken orally prior to one MRI study visit.
DRUG	Placebo	Participants will be screened for lactose intolerance. Total dosing will be calculated to match the mg needed for the indomethacin study visit.
DIAGNOSTIC_TEST	MRI	CBF testing will be performed on 3T MRI scanners (GE Healthcare)

Timeline

• Start date: 2026-07-01
• Primary completion: 2031-07-01
• Completion: 2031-07-01
• First posted: 2025-10-20
• Last updated: 2025-10-20

Regulatory

• FDA-regulated drug study