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HYPEROXIA Responses and ROS

Primary Purpose

Cerebrovascular Disorders

Status
Not yet recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Antioxidant Cocktail
Placebo
Sponsored by
University of Wisconsin, Madison
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Cerebrovascular Disorders

Eligibility Criteria

18 Years - 40 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Age between ≥18 - ≤40 years Exclusion Criteria: 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 myocardial infarction coronary heart disease congestive heart failure heart surgery prediabetes diabetes mellitus (type 1, type 2, MODY, or others) sleep apnea hypertension some autoimmune diseases, such as inflammatory bowel disease or systemic lupus erythematosus (exclusion at discretion of reviewing MD) Current smoking, defined as the use of tobacco or nicotine products >5 times in the past 30 days. Cardiovascular medication use NSAID sensitivity Any contraindications of having an MRI o (e.g. the requirement of anxiolytics in order to complete an MRI scan) Irregular menstrual cycle (females only) Medical conditions that can affect the menstrual cycle, such as hyperprolactinemia, prolactinoma, hypercortisolemia, and congenital adrenal hyperplasia (females only) Pregnancy, breast feeding, or plans to conceive within the next 3 months (females only) Polycystic ovary syndrome (females only) Hirsutism defined as unwanted and/or excessive hair growth on the face, chest, or back (females only) Levonorgestrel intrauterine device (IUD) (females only) Hormonal birth control will not be allowed in women, in order to control for high variability between type, dose, and route of therapy. However, in discussion with Dr. Davis (Co-I) and Dr. Laura Cooney M.D., physician experts in medical and reproductive endocrinology and infertility, there are two broad exceptions to this birth control criteria: Copper intrauterine devices (IUDs) will be allowed as they do not change systemic sex hormone levels). Women currently taking hormonal birth control (i.e. contraceptive pills, patch, ring) for contraception only (not for a medical condition such as those listed in exclusion criteria above) may consider temporarily stopping to become eligible for enrollment. Hormonal birth control must be stopped at least one month prior to Study Visit 1 to provide time for menstruation to resume. Then stoppage continues through the last planned study visit. Screening information will be reviewed by endocrinology physicians to determine eligibility and timing on this issue (details below).

Sites / Locations

  • University of Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Antioxidant Cocktail

Placebo

Arm Description

The first dose will be 500 mg vitamin C, 200 IU vitamin E, and 300 mg of alpha lipoic acid 120 minutes before MRI. The second dose will be 500 mg vitamin C, 400 IU vitamin E, and 300 mg of alpha lipoic acid 60 minutes before MRI.

Placebo 120 minutes before MRI, followed by another dose of placebo 60 minutes before MRI.

Outcomes

Primary Outcome Measures

Cerebral Blood Flow: Normoxia
Participants will be randomized to AOC or placebo. Normoxia measures will be collected under each condition in the MRI over 2 study visits.
Cerebral Blood Flow: Hyperoxia
Participants will be randomized to AOC or placebo. Hyperoxia measures will be collected under each condition in the MRI over 2 study visits.

Secondary Outcome Measures

Full Information

First Posted
July 6, 2023
Last Updated
September 5, 2023
Sponsor
University of Wisconsin, Madison
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT05958303
Brief Title
HYPEROXIA Responses and ROS
Official Title
Human Cerebral Blood Flow Regulation: Sex, Mechanism, and Stress Differences
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 2023 (Anticipated)
Primary Completion Date
July 2025 (Anticipated)
Study Completion Date
July 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Wisconsin, Madison
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
30 participants (15 males and 15 females) who are ≥18 - ≤ 40 years old and considered healthy will be enrolled into this study to test the role of reactive oxygen species (ROS) in regulating cerebral blood flow (CBF). Participants can expect to be on study for 2 study visits over a 6 month period.
Detailed Description
Objective: The current objective is to determine whether biological sex influences CBF control in hyperoxia in healthy young adults without confounds of age or disease. The investigators will address 3 specific questions: Are cerebral vasoconstrictor responses to hyperoxia greater in men? Do all brain regions respond equally, or are there regional differences-possibly varying by sex? Do ROS regulate the decrease in CBF in a sex specific fashion? 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: This study includes 30 total participants; (15 males and 15 females) who are ≥18 - ≤ 40 years old and considered healthy. Approach: CBF testing will be performed in research-dedicated MRI systems on UW campus. Participants will experience normoxia followed by hyperoxia conditions during each of the 2 study visits. Study design focuses on the use of an acute oral antioxidant cocktail (AOC) to test ROS signaling as a potential mechanism explaining sex differences in CBF control. To do this, 2 MRI visits in a double-blind placebo-controlled design will be conducted.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cerebrovascular Disorders

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Antioxidant Cocktail
Arm Type
Experimental
Arm Description
The first dose will be 500 mg vitamin C, 200 IU vitamin E, and 300 mg of alpha lipoic acid 120 minutes before MRI. The second dose will be 500 mg vitamin C, 400 IU vitamin E, and 300 mg of alpha lipoic acid 60 minutes before MRI.
Arm Title
Placebo
Arm Type
Active Comparator
Arm Description
Placebo 120 minutes before MRI, followed by another dose of placebo 60 minutes before MRI.
Intervention Type
Dietary Supplement
Intervention Name(s)
Antioxidant Cocktail
Other Intervention Name(s)
AOC
Intervention Description
Total dosing of 1000 mg vitamin C, 600 IU vitamin E, and 600 mg of alpha lipoic acid.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Cerebral Blood Flow: Normoxia
Description
Participants will be randomized to AOC or placebo. Normoxia measures will be collected under each condition in the MRI over 2 study visits.
Time Frame
up to 6 months
Title
Cerebral Blood Flow: Hyperoxia
Description
Participants will be randomized to AOC or placebo. Hyperoxia measures will be collected under each condition in the MRI over 2 study visits.
Time Frame
up to 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Age between ≥18 - ≤40 years Exclusion Criteria: 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 myocardial infarction coronary heart disease congestive heart failure heart surgery prediabetes diabetes mellitus (type 1, type 2, MODY, or others) sleep apnea hypertension some autoimmune diseases, such as inflammatory bowel disease or systemic lupus erythematosus (exclusion at discretion of reviewing MD) Current smoking, defined as the use of tobacco or nicotine products >5 times in the past 30 days. Cardiovascular medication use NSAID sensitivity Any contraindications of having an MRI o (e.g. the requirement of anxiolytics in order to complete an MRI scan) Irregular menstrual cycle (females only) Medical conditions that can affect the menstrual cycle, such as hyperprolactinemia, prolactinoma, hypercortisolemia, and congenital adrenal hyperplasia (females only) Pregnancy, breast feeding, or plans to conceive within the next 3 months (females only) Polycystic ovary syndrome (females only) Hirsutism defined as unwanted and/or excessive hair growth on the face, chest, or back (females only) Levonorgestrel intrauterine device (IUD) (females only) Hormonal birth control will not be allowed in women, in order to control for high variability between type, dose, and route of therapy. However, in discussion with Dr. Davis (Co-I) and Dr. Laura Cooney M.D., physician experts in medical and reproductive endocrinology and infertility, there are two broad exceptions to this birth control criteria: Copper intrauterine devices (IUDs) will be allowed as they do not change systemic sex hormone levels). Women currently taking hormonal birth control (i.e. contraceptive pills, patch, ring) for contraception only (not for a medical condition such as those listed in exclusion criteria above) may consider temporarily stopping to become eligible for enrollment. Hormonal birth control must be stopped at least one month prior to Study Visit 1 to provide time for menstruation to resume. Then stoppage continues through the last planned study visit. Screening information will be reviewed by endocrinology physicians to determine eligibility and timing on this issue (details below).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shawn Bolin, MS
Phone
608-263-6308
Email
sbolin@wisc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William G Schrage, PhD
Organizational Affiliation
University of Wisconsin, Madison
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Wisconsin
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53705
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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HYPEROXIA Responses and ROS

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