Trial Outcomes & Findings for Human Cerebral Blood Flow Regulation (NCT NCT04265053)

Last Updated: 2026-06-12

Results Overview

CVC is the ratio between Cerebral Blood Flow (CBF) and blood pressure (BP). Change in CVC in response to hypoxia between male and female groups, where baseline CVC is subtracted from hypoxia CVC. Hypoxia typically lasts about 20 minutes. The hypothesis is that women will exhibit 50-60% more vasodilation in response to hypoxia \[Aim 1\].

Recruitment status

COMPLETED

Study phase

EARLY_PHASE1

Target enrollment

42 participants

Primary outcome timeframe

up to 75 minutes for entire visit, but hypoxia lasts about 20 minutes

Results posted on

2026-06-12

Participant Flow

Recruited forty-two (42) otherwise healthy adults between 18-40 years of age inclusive composed of 30 males and 27 females. These 42 participants completed both Aims 1 and 2 (both Aims completed in 2 study visits). Participants were recruited through the University's email of faculty staff and students, online advertisements, newspaper advertisements, paper fliers, and by word of mouth.

Originally, healthy adults between 18-40 years of age were recruited for a study on NOS and COX to test sex differences in CBF. After the study was unable to obtain the drug (L-NMMA) to test the NOS mechanism, the protocol was amended to remove the NOS intervention. The new version of the study used Indomethacin to test COX as a potential mechanism explaining sex differences in CBF control. To do this, 2 MRI visits were conducted in a double-blind placebo controlled design.

Participant milestones

Participant milestones
Measure	Male Males visit MRI twice. Once for indomethacin visit (hypoxia + hypercapnia), and once for placebo visit (hypoxia + hypercapnia). These 2 MRI visits are conducted in a double-blind placebo controlled design. CBF measured via MRI sequences, and hemodynamics monitored for safety/research.	Female Females visit MRI twice. Once for indomethacin visit (hypoxia + hypercapnia), and once for placebo visit (hypoxia + hypercapnia). These 2 MRI visits are conducted in a double-blind placebo controlled design. CBF measured via MRI sequences, and hemodynamics monitored for safety/research.
Overall Study STARTED	24	18
Overall Study Hypoxia Analysis Population	22	17
Overall Study Hypercapnia Analysis Population	15	15
Overall Study Completed Indomethacin Condition	19	16
Overall Study Completed Placebo Condition	22	17
Overall Study COMPLETED	22	17
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Male Males visit MRI twice. Once for indomethacin visit (hypoxia + hypercapnia), and once for placebo visit (hypoxia + hypercapnia). These 2 MRI visits are conducted in a double-blind placebo controlled design. CBF measured via MRI sequences, and hemodynamics monitored for safety/research.	Female Females visit MRI twice. Once for indomethacin visit (hypoxia + hypercapnia), and once for placebo visit (hypoxia + hypercapnia). These 2 MRI visits are conducted in a double-blind placebo controlled design. CBF measured via MRI sequences, and hemodynamics monitored for safety/research.
Overall Study MRI technical issues - missing data	2	1

Baseline Characteristics

Male vs Female

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Male n=24 Participants Males visit MRI twice. Once for indomethacin visit (hypoxia + hypercapnia), and once for placebo visit (hypoxia + hypercapnia). These 2 MRI visits are conducted in a double-blind placebo controlled design. CBF measured via MRI sequences, and hemodynamics monitored for safety/research.	Female n=18 Participants Females visit MRI twice. Once for indomethacin visit (hypoxia + hypercapnia), and once for placebo visit (hypoxia + hypercapnia). These 2 MRI visits are conducted in a double-blind placebo controlled design. CBF measured via MRI sequences, and hemodynamics monitored for safety/research.	Total n=42 Participants Total of all reporting groups
Age, Customized 18-40 years	24 Participants n=9 Participants	18 Participants n=27 Participants	42 Participants n=267 Participants
Sex: Female, Male Female	0 Participants n=9 Participants • Male vs Female	18 Participants n=27 Participants • Male vs Female	18 Participants n=267 Participants • Male vs Female
Sex: Female, Male Male	24 Participants n=9 Participants • Male vs Female	0 Participants n=27 Participants • Male vs Female	24 Participants n=267 Participants • Male vs Female
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=9 Participants	1 Participants n=27 Participants	1 Participants n=267 Participants
Race (NIH/OMB) Asian	2 Participants n=9 Participants	3 Participants n=27 Participants	5 Participants n=267 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=9 Participants	0 Participants n=27 Participants	0 Participants n=267 Participants
Race (NIH/OMB) Black or African American	1 Participants n=9 Participants	0 Participants n=27 Participants	1 Participants n=267 Participants
Race (NIH/OMB) White	21 Participants n=9 Participants	14 Participants n=27 Participants	35 Participants n=267 Participants
Race (NIH/OMB) More than one race	0 Participants n=9 Participants	0 Participants n=27 Participants	0 Participants n=267 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=9 Participants	0 Participants n=27 Participants	0 Participants n=267 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=9 Participants	2 Participants n=27 Participants	7 Participants n=267 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants n=9 Participants	15 Participants n=27 Participants	32 Participants n=267 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=9 Participants	1 Participants n=27 Participants	3 Participants n=267 Participants

PRIMARY outcome

Timeframe: up to 75 minutes for entire visit, but hypoxia lasts about 20 minutes

Outcome measures

Outcome measures
Measure	Hypoxia Male Indomethacin n=19 Participants Males visit MRI twice. Once for indomethacin visit (hypoxia + hypercapnia), and once for placebo visit (hypoxia + hypercapnia). Results reported for hypoxia, indomethacin condition.	Hypoxia Male Placebo n=22 Participants Males visit MRI twice. Once for indomethacin visit (hypoxia + hypercapnia), and once for placebo visit (hypoxia + hypercapnia). Results reported for hypoxia, placebo condition.	Hypoxia Female Indomethacin n=16 Participants Females visit MRI twice. Once for indomethacin visit (hypoxia + hypercapnia), and once for placebo visit (hypoxia + hypercapnia). Results reported for hypoxia, indomethacin condition.	Hypoxia Female Placebo n=17 Participants Females visit MRI twice. Once for indomethacin visit (hypoxia + hypercapnia), and once for placebo visit (hypoxia + hypercapnia). Results reported for hypoxia, placebo condition.
Cerebrovascular Conductance (CVC) in Response to Hypoxia, Male vs Female	2.44 mL/100g/min Standard Deviation 4.59	4.90 mL/100g/min Standard Deviation 10.4	4.32 mL/100g/min Standard Deviation 4.27	9.04 mL/100g/min Standard Deviation 11.0

PRIMARY outcome

Timeframe: up to 75 minutes for entire visit, but hypercapnia lasts about 10-15 minutes

CVC is the ratio between Cerebral Blood Flow (CBF) and blood pressure (BP). Change in CVC in response to hypercapnia between male and female groups, where CBF is normalized for BP. Baseline CVC will be subtracted from hypercapnia CVC. Hypercapnia typically lasts about 10-15 minutes.The hypothesis is that hypercapnic vasodilation will be similar between groups \[Aim 1B\].

Outcome measures

Outcome measures
Measure	Hypoxia Male Indomethacin n=15 Participants Males visit MRI twice. Once for indomethacin visit (hypoxia + hypercapnia), and once for placebo visit (hypoxia + hypercapnia). Results reported for hypoxia, indomethacin condition.	Hypoxia Male Placebo n=15 Participants Males visit MRI twice. Once for indomethacin visit (hypoxia + hypercapnia), and once for placebo visit (hypoxia + hypercapnia). Results reported for hypoxia, placebo condition.	Hypoxia Female Indomethacin n=15 Participants Females visit MRI twice. Once for indomethacin visit (hypoxia + hypercapnia), and once for placebo visit (hypoxia + hypercapnia). Results reported for hypoxia, indomethacin condition.	Hypoxia Female Placebo n=15 Participants Females visit MRI twice. Once for indomethacin visit (hypoxia + hypercapnia), and once for placebo visit (hypoxia + hypercapnia). Results reported for hypoxia, placebo condition.
CVC in Response to Hypercapnia, Male vs Female	0.8 mL/100g/min Standard Deviation 2.4	6.0 mL/100g/min Standard Deviation 2.1	2.4 mL/100g/min Standard Deviation 1.6	4.8 mL/100g/min Standard Deviation 1.9

Adverse Events

Male Participants - Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Male Participants - Indo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Female Participants - Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Female Participants - Indo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Male Participants - Placebo n=24 participants at risk Males visit MRI twice. Once for indomethacin visit (hypoxia + hypercapnia), and once for placebo visit (hypoxia + hypercapnia). These 2 MRI visits are conducted in a double-blind placebo controlled design. CBF measured via MRI sequences, and hemodynamics monitored for safety/research.	Male Participants - Indo n=24 participants at risk Males visit MRI twice. Once for indomethacin visit (hypoxia + hypercapnia), and once for placebo visit (hypoxia + hypercapnia). These 2 MRI visits are conducted in a double-blind placebo controlled design. CBF measured via MRI sequences, and hemodynamics monitored for safety/research.	Female Participants - Placebo n=18 participants at risk Females visit MRI twice. Once for indomethacin visit (hypoxia + hypercapnia), and once for placebo visit (hypoxia + hypercapnia). These 2 MRI visits are conducted in a double-blind placebo controlled design. CBF measured via MRI sequences, and hemodynamics monitored for safety/research.	Female Participants - Indo n=18 participants at risk Females visit MRI twice. Once for indomethacin visit (hypoxia + hypercapnia), and once for placebo visit (hypoxia + hypercapnia). These 2 MRI visits are conducted in a double-blind placebo controlled design. CBF measured via MRI sequences, and hemodynamics monitored for safety/research.
Injury, poisoning and procedural complications Brusing	8.3% 2/24 • Number of events 2 • data collected at screening and 2, 1-hour study visits, over approximately 6 months)	0.00% 0/24 • data collected at screening and 2, 1-hour study visits, over approximately 6 months)	16.7% 3/18 • Number of events 3 • data collected at screening and 2, 1-hour study visits, over approximately 6 months)	11.1% 2/18 • Number of events 2 • data collected at screening and 2, 1-hour study visits, over approximately 6 months)
General disorders Headache	4.2% 1/24 • Number of events 1 • data collected at screening and 2, 1-hour study visits, over approximately 6 months)	0.00% 0/24 • data collected at screening and 2, 1-hour study visits, over approximately 6 months)	5.6% 1/18 • Number of events 1 • data collected at screening and 2, 1-hour study visits, over approximately 6 months)	0.00% 0/18 • data collected at screening and 2, 1-hour study visits, over approximately 6 months)
General disorders Met Stopping Guidelines	0.00% 0/24 • data collected at screening and 2, 1-hour study visits, over approximately 6 months)	0.00% 0/24 • data collected at screening and 2, 1-hour study visits, over approximately 6 months)	11.1% 2/18 • Number of events 2 • data collected at screening and 2, 1-hour study visits, over approximately 6 months)	0.00% 0/18 • data collected at screening and 2, 1-hour study visits, over approximately 6 months)

Additional Information

William Schrage, PhD

University of Wisconsin - Madison

Phone: (608) 262-7715

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place