Human Cerebral Blood Flow Regulation

Summary

This study tests basic differences in how men and women control brain (cerebral) blood flow (CBF), at rest and under stress. The stress is low oxygen or high carbon dioxide. The investigators hypothesize that sex differences per se, plus sex hormone differences, drive different signals in blood vessels that change the way CBF is regulated. The investigators will test these mechanisms with medicine infusions during stress, and measure CBF using state-of-the-art MRI approaches. Research confounding variables like aging and disease will be mitigated by comparing younger adults (18-40 years old).

Conditions

• Cerebral Arterial Diseases

Interventions

DRUG

Indomethacin 25 MG/50 MG

Indomethacin is a nonsteroidal anti-inflammatory drug commonly used to reduce fever, pain, stiffness, and swelling from inflammation. It prevents the production of prostaglandins, endogenous signaling molecules known to cause symptoms from inflammation. Indomethacin is used to test COX as a potential mechanism explaining sex differences in CBF control. Indomethacin usage is IND exempt.

DRUG

Placebo - Lactose

Participants will be screened for lactose intolerance. Total dosing will be calculated to match the mg needed for the indomethacin study visit. Placebo usage is IND exempt.

DRUG

Ganirelix Acetate

Gonadotropin-Releasing Hormone (GnRH) antagonist ganirelix acetate as a model to isolate estrogen and testosterone effects on the cerebrovascular system. Participants receive daily injections of ganirelix for 12-14 days for Aim 3 studies only. This will be overseen by clinical endocrinologists. Both males and females receive this treatment in Aim 3.

DRUG

Testosterone Transdermal Product

In Aim 3, males receive this for 7-9 days of the ganirelix treatment.

DRUG

Estradiol Topical

In Aim 3, females receive this for 7-9 days of the ganirelix treatment.

DRUG

Antacid

Participants will be given a dose of over-the-counter antacid to combat the gastrointestinal distress expected from Indomethacin. Participants will be given a dose of over-the-counter antacid during the placebo visit to mimic the indomethacin study visit. Antacid is IND exempt.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)

  collaborator NIH

• University of Wisconsin, Madison

  lead OTHER

Principal Investigators

• William Schrage, PhD · University of Wisconsin, Madison

Study Design

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

40 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2021-04-12

Primary Completion

2025-03-31

Completion

2025-05-31

FDA Drug

Yes

Countries

• United States

Study Locations