Metabolic SyndromeEarly Phase 1NCT07218653
Human Cerebrovascular Blood Flow and Sex Differences in Metabolic Syndrome
A Early Phase 1 study testing Indomethacin and MRI in people with Metabolic Syndrome, run by University of Wisconsin, Madison at 1 site in United States.
Trial 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: Healthy Controls versus participants with MetSyn. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Metabolic Syndrome
- What is being tested?
- Indomethacin and MRI
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2026to Jul 2031
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 18-45 years old
- Normal fasting values for blood glucose (less than 100 g/dl)
- Normal values for lipids (LDL cholesterol less than 130 mg/dl, triglycerides less than 150 mg/dl) and HDL (men greater than 40, women greater than 50 mg/dl)
- Women must have a predictable menstrual cycle. Females will be studied on cycle days 1-7 to minimize sex hormone differences and their potential confounding effects on vascular outcomes. Oral contraceptives are allowed, and women will be studied during their placebo phase.
- 18-45 years old
- Meet at least 3 of the 5 ATP MetSyn criteria. These are:
Show all 11Show fewer
- Waist circumference greater than 102 cm (males) or 82 cm (females)
- Triglycerides greater than 150 mg/dL
- HDL cholesterol less than 40 mg/dL (males) or 50 mg/dL (females)
- Blood pressure greater than or equal to 130/85 mmHg
- Fasting plasma glucose greater than 110 mg/dL
Who cannot join
- Body Mass Index (BMI) greater than or equal to 25 kg/m2
- Blood pressure over 130/80 mmHg
- Meeting any of the 5 MetSyn criteria listed above.
- Current smoker, defined as more than 5 cigarettes over past 30 days
- Current diagnosis or history of:
- peripheral vascular disease
Show all 29Show fewer
- hepatic disease
- renal disease
- lung disease
- gastrointestinal disorders/bleeding
- hematologic disease
- stroke
- myocardial infarction
- coronary heart disease
- congestive heart failure
- heart surgery
- sleep apnea
- autoimmune diseases
- HIV
- traumatic brain injury, concussion, stroke, or seizures
- Asthma
- Polycystic ovarian syndrome
- Type II diabetes
- Currently pregnant or breastfeeding
- Current musculoskeletal injury
- Medication use known to influence cardiovascular function, other than contraceptive hormones. Broadly, the classes of drugs relate to treating blood pressure, diabetes, cholesterol.
- Claustrophobia
- Lactose intolerance
- Magnesium-restricted diet
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
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: Healthy Controls versus participants with MetSyn.
Read the 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):
- Exercise Visit: VO2 Max, DEXA for adiposity quantification, NIH Toolbox to assess neurocognitive function
- MRI Visit 1: blinded to either Placebo or Indomethacin
- MRI Visit 2: blinded to either Placebo or Indomethacin
- Conditions
- Metabolic Syndrome
- Being tested
- Indomethacin, Placebo, MRI
- Keywords
- Cerebral Blood Flow, CBF, COX, Metabolic Syndrome, MetSyn
- Medical subject headings
- Metabolic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IndomethacinDrug
Also called Indo
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.
PlaceboDrug
Also called Lactose
Participants will be screened for lactose intolerance. Total dosing will be calculated to match the mg needed for the indomethacin study visit.
MRIDiagnostic test
Also called Magnetic Resonance Imaging
CBF testing will be performed on 3T MRI scanners (GE Healthcare)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Indomethacin; Drug: Placebo; Diagnostic Test: MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cerebral Blood Flow
Data collected via MRI under one of 2 conditions: placebo or indomethacin.
Measured: data collected over 2 study visits that must be completed within 6 months
Secondary outcomes (7)
Cardiorespiratory Fitness: VO2 max
Graded exercise test to assess maximal aerobic capacity, reported as VO2 max (milliliters of oxygen consumed per kilogram of body weight per minute)
Measured: data collected at one study visit (must be completed within 6 months)
Body Fat Mass
Dual-energy x-ray absorptiometry (DEXA) to measure fat mass.
Measured: data collected at one study visit (must be completed within 6 months)
Cognitive Testing: Flanker Inhibitory Control and Attention
NIH Toolbox to assess neurocognitive function. The Flanker test is a measure of executive function and is scored using a T-score where 100 is the average, higher scores indicate better performance.
Measured: data collected at one study visit (must be completed within 6 months)
Cognitive Testing: Pattern Comparison Processing Speed Test
NIH Toolbox to assess neurocognitive function. The Pattern Comparison Processing Speed Test measures how many correct responses the participant has within 90 seconds. There is a maximum of 130 items.
Measured: data collected at one study visit (must be completed within 6 months)
Cognitive Testing: List Sorting Working Memory Test
NIH Toolbox to assess neurocognitive function. The List Sorting Working Memory Test is a measure of recall and sorting. Participants scores reflect the number of items recalled and appropriately sorted up to 28 items maximum.
Measured: data collected at one study visit (must be completed within 6 months)
Cognitive Testing: Dimensional Change Card Sort Test
NIH Toolbox to assess neurocognitive function. The Dimensional Change Card Sort Test measures accuracy: the number of accurate responses, up to a maximum of 40.
Measured: data collected at one study visit (must be completed within 6 months)
Cognitive Testing: Picture Vocabulary Test
NIH Toolbox to assess neurocognitive function. The Picture Vocabulary Test has the participant hear a word and then pick from one of four pictures that best represents the word. It is scored using a T-score where 100 is the average, higher scores indicate better performance.
Measured: data collected at one study visit (must be completed within 6 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2025
- Study startNov 2026 (estimated)
- Primary completionJul 2031 (estimated)
- Study completionJul 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metabolic SyndromeStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Participants are randomized to Placebo vs Indomethacin for 2 MRI visits such that they are their own control.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- William Schrage, PhD, Principal investigator, UW Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07218653
- Sponsor's protocol ID
- 2025-1859
- Other IDs
- 1R01HL179276, School of Educ / Kinesiology, Protocol Version 2/8/2026
- Status last verified
- Oct 2026
- First submitted
- 16 Oct 2025
- Last updated
- 2 Nov 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Human Cerebrovascular Blood Flow and Sex Differences in Metabolic Syndrome
- ClinicalTrials.gov ID
- NCT07218653
- Acronym / sponsor ID
- 2025-1859
- Conditions
- Metabolic Syndrome
- Keywords
- Cerebral Blood Flow, CBF, COX, Metabolic Syndrome, MetSyn
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Nov 2026 (estimated)
- Primary completion
- Jul 2031 (estimated)
- Study completion
- Jul 2031 (estimated)
- First posted
- 20 Oct 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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: Healthy 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):
- Exercise Visit: VO2 Max, DEXA for adiposity quantification, NIH Toolbox to assess neurocognitive function
- MRI Visit 1: blinded to either Placebo or Indomethacin
- MRI Visit 2: blinded to either Placebo or Indomethacin
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants are randomized to Placebo vs Indomethacin for 2 MRI visits such that they are their own control.
| Arm | Type | Receives |
|---|---|---|
| Healthy controls | Experimental | Drug: Indomethacin, Drug: Placebo, Diagnostic Test: MRIMale 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. |
| Metabolic Syndrome | Experimental | Drug: Indomethacin, Drug: Placebo, Diagnostic Test: MRIMale 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. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 18-45 years old
- Normal fasting values for blood glucose (less than 100 g/dl)
- Normal values for lipids (LDL cholesterol less than 130 mg/dl, triglycerides less than 150 mg/dl) and HDL (men greater than 40, women greater than 50 mg/dl)
- Women must have a predictable menstrual cycle. Females will be studied on cycle days 1-7 to minimize sex hormone differences and their potential confounding effects on vascular outcomes. Oral contraceptives are allowed, and women will be studied during their placebo phase.
- 18-45 years old
Key exclusion criteria (29 listed)
- Body Mass Index (BMI) greater than or equal to 25 kg/m2
- Blood pressure over 130/80 mmHg
- Meeting any of the 5 MetSyn criteria listed above.
- Current smoker, defined as more than 5 cigarettes over past 30 days
- Current diagnosis or history of:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IndomethacinAlso: IndoIndomethacin 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 | Healthy controls, Metabolic Syndrome |
| PlaceboAlso: LactoseParticipants will be screened for lactose intolerance. Total dosing will be calculated to match the mg needed for the indomethacin study visit. | Drug | Healthy controls, Metabolic Syndrome |
| MRIAlso: Magnetic Resonance ImagingCBF testing will be performed on 3T MRI scanners (GE Healthcare) | Diagnostic test | Healthy controls, Metabolic Syndrome |
Primary outcome
Cerebral Blood Flow
Time frame: data collected over 2 study visits that must be completed within 6 months
Data collected via MRI under one of 2 conditions: placebo or indomethacin.
7 secondary outcomes
Cardiorespiratory Fitness: VO2 max
Time frame: data collected at one study visit (must be completed within 6 months)
Body Fat Mass
Time frame: data collected at one study visit (must be completed within 6 months)
Cognitive Testing: Flanker Inhibitory Control and Attention
Time frame: data collected at one study visit (must be completed within 6 months)
Cognitive Testing: Pattern Comparison Processing Speed Test
Time frame: data collected at one study visit (must be completed within 6 months)
Cognitive Testing: List Sorting Working Memory Test
Time frame: data collected at one study visit (must be completed within 6 months)
Cognitive Testing: Dimensional Change Card Sort Test
Time frame: data collected at one study visit (must be completed within 6 months)
Cognitive Testing: Picture Vocabulary Test
Time frame: data collected at one study visit (must be completed within 6 months)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2026.
- Individual participant dataSharing planned: Yes
Related trials for Metabolic Syndrome
RecruitingObservational study
Defining the Natural History of Squamous Cell Carcinoma in Fanconi Anemia
Fanconi Anemia, Inherited Bone Marrow Failure Syndrome
Not yet recruitingPhase 2
Osilodrostat for Glycemic Control in Mild Autonomous Cortisol Secretion (MACS) With Difficult-To-Control Type 2 Diabetes - A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study
Mild Autonomous Cortisol Secretion (MACS), Diabetes Mellitus (Type 2)
Active, not recruiting
Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
Neuromuscular Diseases (NMD), Amyotrophic Lateral Sclerosis
Not yet recruitingObservational study
Clinical Genetics Branch Eligibility Screening Survey
Melanoma, Li-Fraumeni Syndrome
Not yet recruitingPhase 2
Effects of Meal Macronutrients on Postprandial Lipids
Nephrotic Syndrome, Lipodystrophy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
William Schrage, PhD principal investigator
UW Madison
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Indomethacin and MRI in people with Metabolic Syndrome, run by University of Wisconsin, Madison at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Shawn Bolin, MS (608-263-6308, sbolin@wisc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cerebral Blood Flow (time frame: data collected over 2 study visits that must be completed within 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026.