Effect of Age and Fitness on Vascular Function and Oxidative Stress During Acute Inflammation

Phase 4

Terminated

Conditions: Inflammation
Aging

Interventions: Biological: Typhoid Vaccine
Dietary Supplement: Ascorbic Acid

Registration Number: NCT03889158

Lead Sponsor: University of Illinois at Chicago

Brief Summary: This study focuses on whether high cardiorespiratory fitness in older adults has a protective effect on the vascular response to acute inflammation in comparison to low-fit older and young adults.

Detailed Description: Acute and chronic inflammation both increase cardiovascular disease risk, especially with aging, which may be due to vascular dysfunction. Aging and inflammation also lead to increased oxidative stress, which impairs vascular function. During acute inflammation, endothelial function is altered differently in younger and older adults with decreases in endothelial function in younger, but not older adults. However, cardiorespiratory fitness is cardio-protective, impacting inflammation, vascular function, and oxidative stress. During acute inflammation, moderately fit older adults exhibit similar responses to younger adults, suggesting preserved endothelial reactivity. However, whether the protective mechanism is oxidative stress has not been confirmed. Furthermore, it is undetermined whether the vascular dysfunction is further propagated down the arterial tree during acute inflammation to the microvasculature.

The aims of this research study are to determine if age and fitness moderate the vascular response to acute inflammation and to determine if antioxidant administration eliminates vascular dysfunction during acute inflammation. The results from this study will help to elucidate if fitness is a protective and preventive measure to ameliorate the detrimental cardiovascular response to acute inflammation. Thus, this study may provide health professionals with a behavioral intervention to reduce cardiovascular disease burden in the rapidly growing aging population.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 35

Inclusion Criteria

Males and females willing to provide informed consent
18-35 or 55-75 years of age
Non-smoker
No use of anti-inflammatory medication within last 2 weeks
Aerobically trained (defined as performing aerobic exercise on ≥4 days/week, for ≥30 minutes, for at least the past 3 months AND a VO2max ≥75th age- and sex-specific percentile according to ACSM)
/// OR /// Sedentary (defined as being involved in less than 30 minutes of moderately-intense physical activity per day, < 3 days/week AND a VO2max ≤ 50th age- and sex-specific percentile according to ACSM)

Exclusion Criteria

Body mass index >35 kg/m2
Pregnancy, hormone replacement therapy, or peri-menopausal
Known cardiovascular (i.e. atherosclerosis, uncontrolled hypertension, stroke, myocardial infarction, etc.), inflammatory (i.e. Crohn's disease, arthritis, etc.), or metabolic (i.e. Diabetes mellitus) disease
Medications known to influence cardiovascular outcomes (i.e. heart rate, blood pressure, endothelial function, etc)
Regular use of medications to reduce inflammation (NSAIDS, aspirin, steroids, etc)
Bleeding disorders
Illness, other vaccination, or antioxidant use within 2 weeks prior to screening
Typhoid vaccination within previous 2 years or prior adverse reaction
VO2max in 51st - 74th age- and sex-specific percentile according to ACSM (measured during first testing visit)
Non-English speaking participants

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Acute Inflammation	Typhoid Vaccine	All participants will receive the typhoid vaccination (intramuscular injection, 0.5 mL, 1 time).
Ascorbic Acid	Ascorbic Acid	All participants will receive ascorbic acid (Vit C) on two occasions \[oral pill, 2g, 2x (baseline, during acute inflammation)\].

Primary Outcome Measures

Name	Time	Method
Change in Endothelial Function	Visit 1: At [BASELINE] and 2 hours following Vit C [BASELINE+VIT C]; Visit 2 (>72 hours after Visit 1): At baseline [PRE-INFLAMMATION BASELINE]; Visit 3 (24 hours after Visit 2): At baseline [INFLAMMATION] and 2 hours following Vit C [INFLAMMATION+VIT C]	Flow-mediated dilation - Brachial artery vasodilator function will be noninvasively measured through assessment of brachial artery dilation using ultrasonography. The brachial artery will be imaged proximal to placement of a blood pressure cuff just below the antecubital fossa. Endothelium-dependent dilation of the brachial artery will be measured at baseline and again for 5 minutes following ischemic stimulus (inflation of a blood pressure cuff around the forearm to 250 mmHg for 5 minutes).
Change in Oxidative Stress	Visit 1: At [BASELINE] and 2 hours following Vit C [BASELINE+VIT C]; Visit 2 (>72 hours after Visit 1): At baseline [PRE-INFLAMMATION BASELINE]; Visit 3 (24 hours after Visit 2): At baseline [INFLAMMATION] and 2 hours following Vit C [INFLAMMATION+VIT C]	Oxidized low-density lipoprotein, vitamin C and total antioxidant capacity will be assessed using standard ELISAs from a venous blood draw. The analyses of the oxidized LDL and total antioxidant capacity failed. Only data on Vitamin C are presented.

Secondary Outcome Measures

Name	Time	Method
Change in Arterial Stiffness	Visit 1: At [BASELINE] and 2 hours following Vit C [BASELINE+VIT C]; Visit 2 (>72 hours after Visit 1): At baseline [PRE-INFLAMMATION BASELINE]; Visit 3 (24 hours after Visit 2): At baseline [INFLAMMATION] and 2 hours following Vit C [INFLAMMATION+VIT C]	Central pulse wave velocity - Approximately 20-sec of pressure waveforms will be collected at the brachial, common carotid, and femoral arteries using a high-fidelity strain-gauge transducer. Pulse wave velocity will be calculated from the distances between measurement points and the measured time delay between proximal (carotid) and distal (femoral) waveforms.