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

NCT07218653 | Not Yet Recruiting Early Phase 1 FDA Drug

• 3 other identifiers: R01 MetSynpendingSchool of Educ / Kinesiology
• Study Type: interventional
• Target: 72
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Metabolic Syndrome

Keywords

Cerebral Blood Flow; CBF; COX; Metabolic Syndrome; MetSyn

Outcome Measures

Primary Outcomes (1)

• Cerebral Blood Flow

  Data collected via MRI under one of 2 conditions: placebo or indomethacin.

  data collected over 2 study visits that must be completed within 6 months

Secondary Outcomes (7)

• Cardiorespiratory Fitness: VO2 max

  data collected at one study visit (must be completed within 6 months)

• Body Fat Mass

  data collected at one study visit (must be completed within 6 months)

• Cognitive Testing: Flanker Inhibitory Control and Attention

  data collected at one study visit (must be completed within 6 months)

• Cognitive Testing: Pattern Comparison Processing Speed Test

  data collected at one study visit (must be completed within 6 months)

• Cognitive Testing: List Sorting Working Memory Test

  data collected at one study visit (must be completed within 6 months)

Study Arms (2)

Healthy controls

EXPERIMENTAL

Male and female participants 18-45 without Metabolic Syndrome. On study for 3 visits (up to 6 months). Randomized to either Placebo then Indomethacin or Indomethacin then Placebo for 2 MRI visits.

Drug: Indomethacin; Drug: Placebo; Diagnostic Test: MRI

Metabolic Syndrome

EXPERIMENTAL

Male and female participants, age-matched with Healthy Controls, who have at least 3 defining symptoms of Metabolic Syndrome. Randomized to either Placebo then Indomethacin or Indomethacin then Placebo for 2 MRI visits.

Drug: Indomethacin; Drug: Placebo; Diagnostic Test: MRI

Interventions

Indomethacin DRUG

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.

Also known as: Indo

Healthy controls; Metabolic Syndrome

Placebo DRUG

Participants will be screened for lactose intolerance. Total dosing will be calculated to match the mg needed for the indomethacin study visit.

Also known as: Lactose

Healthy controls; Metabolic Syndrome

MRI DIAGNOSTIC_TEST

CBF testing will be performed on 3T MRI scanners (GE Healthcare)

Also known as: Magnetic Resonance Imaging

Healthy controls; Metabolic Syndrome

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• non-hypertensive (less than 130/80 mmHg)
• non-obese with a Body Mass Index (BMI) less than 30 kilogram per meter squared (kg/m2)
• Normal blood glucose less than 100 grams per deciliter (g/dl)
• Normal lipids; LDL cholesterol less than130 milligrams per deciliter (mg/dl), triglycerides less than 150 mg/dl.
• Women must have a predictable menstrual cycle for MRI scheduling. Females will be studied on cycle days 1-7 (as presented in all preliminary data) to minimize sex hormone differences and their potential confounding effects on vascular outcomes. Oral contraceptives will be allowed in women to increase translatability in findings.
• Meet age criteria plus three or more of the five criteria for MetSyn as defined by ATP, the most common three factors meeting MetSyn criteria will be obesity, prehypertension / hypertension, and low HDL cholesterol.

You may not qualify if:

• Subjects with a diagnostic history of:
• peripheral vascular, hepatic, renal, or hematologic disease
• stroke
• type 1 or 2 diabetes
• sleep apnea
• hypertension (allowed in MetSyn)
• regular tobacco users
• taking cardiovascular medications (e.g., statins, angiotensin II receptor blockers) or metabolic medications (metformin, insulin, semaglutide) or NSAID sensitivity will be excluded.
• In women: pregnancy or polycystic ovarian syndrome (PCOS, to avoid altered testosterone in women).

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• National Institutes of Health (NIH): collaborator

MeSH Terms

Conditions

Metabolic Syndrome

Interventions

Indomethacin; Lactose; Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars; Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• William Schrage, PhD

  UW Madison

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shawn Bolin, MS

CONTACT

608-263-6308; sbolin@wisc.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants are randomized to Placebo vs Indomethacin for 2 MRI visits such that they are their own control.

Study Record Dates

• First Submitted: October 16, 2025
• First Posted: October 20, 2025
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2031
• Study Completion (Estimated): July 1, 2031
• Last Updated: October 20, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF