Human Cerebral Blood Flow Regulation: Sex, Mechanism, and Stress Differences (Phase 2)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Cerebral Blow Flow (CBF): Hormone Suppression Hypoxia Condition
研究概览
简要总结
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.
详细描述
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:
- Are cerebral vasodilator responses greater in women across other physiologic stressors? Do all cerebral vessels respond equally, or are there regional differences-by sex?
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age between ≥18 - ≤40 years inclusive
- •Completed Phase 1: Study 2020-0336
排除标准
- •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
- •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
- •Magnesium-restricted diet
- •Any contraindications of having an MRI
- •(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.
研究组 & 干预措施
Indo First: Hormone Suppression
Participants drug (placebo vs Indo) are randomized prior to first set of MRI visits, while experiencing hormone suppression.
干预措施: Placebo (Drug)
Placebo First: Hormone Suppression
Participants drug (placebo vs Indo) are randomized prior to first set of MRI visits, while experiencing hormone suppression.
干预措施: Indomethacin (Drug)
Placebo First: Hormone Suppression
Participants drug (placebo vs Indo) are randomized prior to first set of MRI visits, while experiencing hormone suppression.
干预措施: Placebo (Drug)
Placebo First: Hormone Suppression
Participants drug (placebo vs Indo) are randomized prior to first set of MRI visits, while experiencing hormone suppression.
干预措施: Orilissa (Drug)
Placebo First: Hormone Suppression
Participants drug (placebo vs Indo) are randomized prior to first set of MRI visits, while experiencing hormone suppression.
干预措施: Estradiol (Drug)
Indo First: Hormone Suppression
Participants drug (placebo vs Indo) are randomized prior to first set of MRI visits, while experiencing hormone suppression.
干预措施: Indomethacin (Drug)
Indo First: Hormone Suppression
Participants drug (placebo vs Indo) are randomized prior to first set of MRI visits, while experiencing hormone suppression.
干预措施: Orilissa (Drug)
Placebo First: Hormone Add-Back
Participants drug (placebo vs Indo) are randomized prior to second set of MRI visits, while experiencing hormone add-back.
干预措施: Indomethacin (Drug)
Placebo First: Hormone Add-Back
Participants drug (placebo vs Indo) are randomized prior to second set of MRI visits, while experiencing hormone add-back.
干预措施: Placebo (Drug)
Placebo First: Hormone Add-Back
Participants drug (placebo vs Indo) are randomized prior to second set of MRI visits, while experiencing hormone add-back.
干预措施: Orilissa (Drug)
Placebo First: Hormone Add-Back
Participants drug (placebo vs Indo) are randomized prior to second set of MRI visits, while experiencing hormone add-back.
干预措施: Testosterone gel (Drug)
Placebo First: Hormone Add-Back
Participants drug (placebo vs Indo) are randomized prior to second set of MRI visits, while experiencing hormone add-back.
干预措施: Anastrozole (Drug)
Placebo First: Hormone Add-Back
Participants drug (placebo vs Indo) are randomized prior to second set of MRI visits, while experiencing hormone add-back.
干预措施: Estradiol (Drug)
Indo First: Hormone Add-Back
Participants drug (placebo vs Indo) are randomized prior to second set of MRI visits, while experiencing hormone add-back.
干预措施: Indomethacin (Drug)
Indo First: Hormone Add-Back
Participants drug (placebo vs Indo) are randomized prior to second set of MRI visits, while experiencing hormone add-back.
干预措施: Placebo (Drug)
Indo First: Hormone Add-Back
Participants drug (placebo vs Indo) are randomized prior to second set of MRI visits, while experiencing hormone add-back.
干预措施: Orilissa (Drug)
Indo First: Hormone Add-Back
Participants drug (placebo vs Indo) are randomized prior to second set of MRI visits, while experiencing hormone add-back.
干预措施: Testosterone gel (Drug)
Indo First: Hormone Add-Back
Participants drug (placebo vs Indo) are randomized prior to second set of MRI visits, while experiencing hormone add-back.
干预措施: Anastrozole (Drug)
Indo First: Hormone Add-Back
Participants drug (placebo vs Indo) are randomized prior to second set of MRI visits, while experiencing hormone add-back.
干预措施: Estradiol (Drug)
结局指标
主要结局
Cerebral Blow Flow (CBF): Hormone Suppression Hypoxia Condition
时间窗: first set of study visits (up to 2 hours) within the first 7 days on study
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.
Cerebral Blow Flow: Hormone Suppression Hypercapnia Condition
时间窗: first set of study visits (up to 2 hours) within the first 7 days on study
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.
Cerebral Blow Flow: Hormone Add-Back Hypoxia Condition
时间窗: second set of study visits (up to 2 hours) within 12-16 days on study
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.
Cerebral Blow Flow: Hormone Add-Back Hypercapnia Condition
时间窗: second set of study visits (up to 2 hours) within 12-16 days on study
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.
次要结局
未报告次要终点