Brain Blood Flow Responses to Stress: Sex Differences

NCT06253702 | Completed Phase 4 DMC FDA Drug

• 4 other identifiers: 2023-05481R01HL150361-01EDUC/KINESIOLOGYProtocol Version 07/01/2024
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

Cerebrovascular Disorders

Outcome Measures

Primary Outcomes (4)

• Cerebral Blow Flow (CBF): Hormone Suppression Hypoxia Condition

  Hypoxia condition will be measured twice via MRI during the first set of study visits under hormone suppression. Reported here is the CBF under hypoxia for the placebo group as compared to the CBF under hypoxia for the Indo group.

  first set of study visits (up to 2 hours) within the first 7 days on study

• Cerebral Blow Flow: Hormone Suppression Hypercapnia Condition

  Hypercapnia condition will be measured twice via MRI during the first set of study visits under hormone suppression. Reported here is the CBF under hypercapnia for the placebo group as compared to the CBF under hypercapnia for the Indo group.

  first set of study visits (up to 2 hours) within the first 7 days on study

• Cerebral Blow Flow: Hormone Add-Back Hypoxia Condition

  Hypoxia condition will be measured twice via MRI during the second set of study visits under hormone add-back. Reported here is the CBF under hypoxia for the placebo group as compared to the CBF under hypoxia for the Indo group.

  second set of study visits (up to 2 hours) within 12-16 days on study

• Cerebral Blow Flow: Hormone Add-Back Hypercapnia Condition

  Hypercapnia condition will be measured twice via MRI during the first set of study visits under hormone add-back. Reported here is the CBF under hypercapnia for the placebo group as compared to the CBF under hypercapnia for the Indo group.

  second set of study visits (up to 2 hours) within 12-16 days on study

Study Arms (4)

Placebo First: Hormone Suppression

EXPERIMENTAL

Participants drug (placebo vs Indo) are randomized prior to first set of MRI visits, while experiencing hormone suppression.

Drug: Indomethacin; Drug: Placebo; Drug: Orilissa; Drug: Estradiol

Indo First: Hormone Suppression

EXPERIMENTAL

Participants drug (placebo vs Indo) are randomized prior to first set of MRI visits, while experiencing hormone suppression.

Drug: Indomethacin; Drug: Placebo; Drug: Orilissa

Placebo First: Hormone Add-Back

EXPERIMENTAL

Participants drug (placebo vs Indo) are randomized prior to second set of MRI visits, while experiencing hormone add-back.

Drug: Indomethacin; Drug: Placebo; Drug: Orilissa; Drug: Testosterone gel; Drug: Anastrozole; Drug: Estradiol

Indo First: Hormone Add-Back

EXPERIMENTAL

Participants drug (placebo vs Indo) are randomized prior to second set of MRI visits, while experiencing hormone add-back.

Drug: Indomethacin; Drug: Placebo; Drug: Orilissa; Drug: Testosterone gel; Drug: Anastrozole; Drug: Estradiol

Interventions

Indomethacin DRUG

to inhibit cyclooxygenase (COX)

Also known as: Indo

Indo First: Hormone Add-Back; Indo First: Hormone Suppression; Placebo First: Hormone Add-Back; Placebo First: Hormone Suppression

Placebo DRUG

Placebo

Indo First: Hormone Add-Back; Indo First: Hormone Suppression; Placebo First: Hormone Add-Back; Placebo First: Hormone Suppression

Orilissa DRUG

to suppress hormones 200mg dose 2x per day (all participants)

Indo First: Hormone Add-Back; Indo First: Hormone Suppression; Placebo First: Hormone Add-Back; Placebo First: Hormone Suppression

Testosterone gel DRUG

50 mg each morning for add back phase (male participants)

Indo First: Hormone Add-Back; Placebo First: Hormone Add-Back

Anastrozole DRUG

1mg/day in men to prevent conversion of testosterone to estradiol

Indo First: Hormone Add-Back; Placebo First: Hormone Add-Back

Estradiol DRUG

Women will receive oral estradiol 2mg/daily

Indo First: Hormone Add-Back; Placebo First: Hormone Add-Back; Placebo First: Hormone Suppression

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age between ≥18 - ≤40 years inclusive
• Completed Phase 1: Study 2020-0336

You may not qualify if:

• Hypertensive
• \> 125 mmHg systolic blood pressure; or
• \> 80 mmHg diastolic blood pressure
• BMI ≥25 kg/m2
• Fasting blood glucose ≥100 mg/dl
• LDL cholesterol ≥130 mg/dl
• Triglycerides ≥150 mg/dl
• Current diagnosis or history of:
• peripheral vascular disease
• hepatic disease
• renal disease
• lung disease
• gastrointestinal disorders/bleeding
• hematologic disease
• stroke

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

MeSH Terms

Conditions

Cerebrovascular Disorders

Interventions

Indomethacin; elagolix; Anastrozole; Estradiol

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• William G Schrage, PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: double-blind placebo controlled design

Study Record Dates

• First Submitted: February 2, 2024
• First Posted: February 12, 2024
• Study Start: July 24, 2024
• Primary Completion: May 31, 2025
• Study Completion: May 31, 2025
• Last Updated: July 18, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)