Development of a Clinically-relevant Test for Assessment of Cerebral Vascular Function

This is an interventional diagnostic trial for Cerebrovascular Disorders focused on measuring brain blood flow, brain vascular function Read More

Inclusion Criteria:

Young and Older Healthy Adults:

• Males and females willing and able to provide informed consent
• Aged between 18-35 years (Young) or 60-80 years (Older)
• Premenopausal women will be tested within 1-4 days after menses begins to control for hormone status
• Women taking oral contraceptives will be allowed to participate and they will be tested in the low hormone or placebo phase
• Postmenopausal women (at least 12 months since last menstrual cycle) who are not on hormone replacement therapy will be eligible
• Sedentary or recreationally active
• Non-tobacco/nicotine users (e.g., cigarettes, chewing tobacco, nicotine gum or patches)
• Laboratory measured systolic blood pressure <140 mmHg and diastolic blood pressure <90 mmHg
• Normal 12-lead ECG (reviewed by a physician)
• Normal clinical results from a medical exam reviewed by a board certified physician (e.g., Medical & Behavioral Health Questionnaire - see attached document)
• Body mass index (BMI) <40 kg/m2 unless athletic/muscular build; calculation = body weight (kg)/height (m2); this criteria is used to ensure subjects will fit inside the LBNP chamber
• Females only: documentation of a negative pregnancy test prior to the familiarization and experimental sessions

Young and Older Chronic Smokers of Tobacco Cigarettes:

The same criteria (a-c and e-i above) as Young and Older Healthy Adults, except:

- Chronic smokers of tobacco cigarettes only (i.e., at least 20 pack year use)

Exclusion Criteria:

Young and Older Healthy Adults:

• Age <18 years, or 40-60 years, or >80 years
• Body mass index (BMI) >40 kg/m2 unless athletic/muscular build; calculation = body weight (kg)/height (m2)
• Regular tobacco/nicotine users within the last 6 months (e.g., cigarettes, chewing tobacco, nicotine gum or patches)
• Not abstaining from the following 24 hours prior to the familiarization session and the experimental session: exercise, alcoholic substances, prescription or non-prescription medications (unless cleared by the medical screener), dietary supplements, herbal medications, caffeinated substances (including coffee, tea (iced or hot), caffeinated energy drinks or sodas).
• Not fasted for at least 3-4 hours prior to the experimental sessions.
• Positive pregnancy test
• Hormone replacement therapy (males and females)
• Females with an erratic/irregular menstrual cycle
• Females who are using a continually-releasing hormonal (e.g., NuvaRing™ or other hormone-releasing vaginal rings, Depo Provera shot, birth control implants such as Nexplanon) and who do not have a regular menstrual cycle
• Use of prescription drugs, non-prescription drugs or herbal medicines known to alter autonomic function unless cleared prior to the study
• Any metabolic disease, except individuals who are on cholesterol-lowering medications (older subjects only; young subjects on cholesterol-lowering medications will be excluded)
• Use of two or more anti-hypertensive medications (older subjects only; young subjects on anti-hypertensive medications will be excluded)
• Use of beta blockers
• Frequent use of bronchodilators
• Use of anti-coagulant therapy
• Current or past history of hyperthyroidism, or other thyroid hormone-related disease
• Signs of cardiovascular abnormalities (e.g., resting systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg; abnormal 12-lead ECG)
• History of cerebrovascular abnormalities (e.g., prior stroke, transient ischemic attacks, epilepsy)
• Known history of atherosclerosis of the carotid arteries (i.e., plaque formation)
• Known history of peripheral artery disease (PAD)
• Concussion and or other loss of consciousness within the past 30 days.
• Autonomic dysfunction (e.g., Shy-Drager Syndrome, Bradbury-Eggleston syndrome, sinus arrhythmia, idiopathic orthostatic hypotension, fainting disorder)
• Respiratory illnesses (e.g., chronic asthma (including exercise-induced asthma), Chronic Obstructive Pulmonary Disease, Reactive Airway Disease)
• History of anaphylaxis
• History of pre-syncopal/syncopal episodes or orthostatic hypotension
• Donated blood within the last 60 days
• History or family history of abnormal blood clotting, clots in deep veins in the legs or pelvis, or blood clots to the lungs
• Known or suspected abdominal hernia
• History of alcohol or drug abuse which inhibits the subject's ability to complete this study
• Known depression, anxiety, or any other mental health issue which inhibits the subject's ability to complete this study

Young and Older Chronic Smokers of Tobacco Cigarettes

The same criteria (a-b and d-dd above) as Young and Older Healthy Adults, except:

- Less than 20 pack year use of tobacco cigarettes, or regular use of other tobacco/nicotine products within the last 6 months (e.g., electronic cigarettes, chewing tobacco, nicotine gum or patches).