Ignite Creation Date:
2025-12-25 @ 4:04 AM
Ignite Modification Date:
2025-12-26 @ 2:59 AM
Study NCT ID:
NCT06253702
Status:
COMPLETED
Last Update Posted:
2025-07-18
First Post:
2024-02-02
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Brain Blood Flow Responses to Stress: Sex Differences
Sponsor:
University of Wisconsin, Madison
Organization:
Study Overview
Official Title:
Human Cerebral Blood Flow Regulation: Sex, Mechanism, and Stress Differences (Phase 2)
Status:
COMPLETED
Status Verified Date:
2025-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Twenty-six otherwise healthy adults between 18-40 years of age composed of 13 males and 13 females will be enrolled in this study to determine how sex and sex hormones influence cerebral blood flow (CBF) control in healthy young adults without confounds of age or disease. Participants can expect to be on study for approximately 16 days.
Detailed Description:
Objective: To determine cerebrovascular control mechanisms in humans and provide mechanistic knowledge to offer new sex-specific therapeutic options for cerebrovascular diseases. The current objective is to determine how sex and sex hormones influence CBF control in healthy young adults without confounds of age or disease.
The central hypothesis is men exhibit reduced cerebral vasodilator function due in part to differences in COX signaling compared to women. Comprehensive CBF data from multi-modal MRI indicate the magnitude of sex differences-as well as the vasodilator mechanisms-are regionally distinct.
The investigators will address 2 specific aims:
1. Are cerebral vasodilator responses greater in women across other physiologic stressors? Do all cerebral vessels respond equally, or are there regional differences-by sex?
2. What mechanisms regulate the increase in CBF to stress; do these differ by sex, or brain region?
This study will be conducted in compliance with federal investigational drug regulations (21 CFR 312) and Good Clinical Practice (GCP) guidelines, as well as state law and institutional policies.
Study Population: Phase 2 include 26 total participants 13 men and 13 women invited back from the Study 2020-0336 (NCT04265053) for Aim 3 who are ≥18 - ≤ 40 years old and considered healthy.
Approach: CBF testing will be performed in research-dedicated 3T magnets. Participants will experience one hypoxia and one hypercapnia trial during each visit. S, study design focuses on the use of Indomethacin to test COX as a potential mechanism explaining sex differences in CBF control. To do this, 4 MRI visits in a double-blind placebo controlled design will be conducted. One set of placebo-Indo visits occurs after the first 4-7 days of sex hormone suppression (with Orilissa) and the second set of MRI visits occurs after 12-16 days of Orilissa while supplementing a single sex hormone by sex.
On day 0 participants will start hormone suppression using Orilissa (male subjects will also start an Anastrozole). After day 2, MRI Visit 1 will be scheduled to occur. Prior to the first study visit the order of drug supplementation will be randomized. Options are: placebo for the first MRI visit, then Indomethacin for the second MRI visit or Indomethacin for the first MRI visit, then placebo for the second MRI visit. After MRI visits 1 and 2 are completed, participants will begin sex hormone add-back (males will receive testosterone and females will receive estradiol). Once participants have been on the hormone add-back protocol for 3-4 days MRI Visits 3 and 4 will be scheduled. Prior to MRI visit 3 the order of drug supplementation will be randomized again.
. Added to protocol on 07/01/2024 = Fecal samples will be collected: at baseline (before beginning Orilissa), 4-8 days after taking the first dose of Orilissa, and 12-16 days after taking the first estradiol or testosterone dose. Subjects will provide 3 fecal samples at home throughout the course of their participation and will take the samples to FedEx to be shipped.
The central hypothesis is men exhibit reduced cerebral vasodilator function due in part to differences in COX signaling compared to women. Comprehensive CBF data from multi-modal MRI indicate the magnitude of sex differences-as well as the vasodilator mechanisms-are regionally distinct.
The investigators will address 2 specific aims:
1. Are cerebral vasodilator responses greater in women across other physiologic stressors? Do all cerebral vessels respond equally, or are there regional differences-by sex?
2. What mechanisms regulate the increase in CBF to stress; do these differ by sex, or brain region?
This study will be conducted in compliance with federal investigational drug regulations (21 CFR 312) and Good Clinical Practice (GCP) guidelines, as well as state law and institutional policies.
Study Population: Phase 2 include 26 total participants 13 men and 13 women invited back from the Study 2020-0336 (NCT04265053) for Aim 3 who are ≥18 - ≤ 40 years old and considered healthy.
Approach: CBF testing will be performed in research-dedicated 3T magnets. Participants will experience one hypoxia and one hypercapnia trial during each visit. S, study design focuses on the use of Indomethacin to test COX as a potential mechanism explaining sex differences in CBF control. To do this, 4 MRI visits in a double-blind placebo controlled design will be conducted. One set of placebo-Indo visits occurs after the first 4-7 days of sex hormone suppression (with Orilissa) and the second set of MRI visits occurs after 12-16 days of Orilissa while supplementing a single sex hormone by sex.
On day 0 participants will start hormone suppression using Orilissa (male subjects will also start an Anastrozole). After day 2, MRI Visit 1 will be scheduled to occur. Prior to the first study visit the order of drug supplementation will be randomized. Options are: placebo for the first MRI visit, then Indomethacin for the second MRI visit or Indomethacin for the first MRI visit, then placebo for the second MRI visit. After MRI visits 1 and 2 are completed, participants will begin sex hormone add-back (males will receive testosterone and females will receive estradiol). Once participants have been on the hormone add-back protocol for 3-4 days MRI Visits 3 and 4 will be scheduled. Prior to MRI visit 3 the order of drug supplementation will be randomized again.
. Added to protocol on 07/01/2024 = Fecal samples will be collected: at baseline (before beginning Orilissa), 4-8 days after taking the first dose of Orilissa, and 12-16 days after taking the first estradiol or testosterone dose. Subjects will provide 3 fecal samples at home throughout the course of their participation and will take the samples to FedEx to be shipped.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 1R01HL150361-01 | NIH | None | https://reporter.nih.gov/quic… | View |
| EDUC/KINESIOLOGY | OTHER | UW Madison | View | |
| Protocol Version 07/01/2024 | OTHER | UW Madison | View |