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

Phase 4TerminatedNCT03889158

University of Illinois at Chicago35 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

Aging Inflammation

Interventions

Typhoid VaccineBIOLOGICAL

All participants will receive the typhoid vaccine.

Ascorbic AcidDIETARY_SUPPLEMENT

All participants will receive ascorbic acid.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Integrative Physiology Laboratory, Suite 158

Chicago, Illinois, United States

Outcomes

Primary Outcomes

Change in Endothelial Function

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).

Time frame: 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]

Change in Oxidative Stress

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 Outcomes

Change in Arterial Stiffness

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.

Data from ClinicalTrials.gov

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