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

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.

Study Overview

• Status: Terminated
• Conditions: Inflammation; Aging
• Intervention / Treatment: Biological: Typhoid Vaccine; Dietary supplement: Ascorbic Acid

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.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60608
      • Integrative Physiology Laboratory, Suite 158

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Acute Inflammation; All participants will receive the typhoid vaccination (intramuscular injection, 0.5 mL, 1 time).	Biological: Typhoid Vaccine; All participants will receive the typhoid vaccine.; Other Names: Typhim Vi; Typhoid Vi Polysaccharide Vaccine
EXPERIMENTAL: Ascorbic Acid; All participants will receive ascorbic acid (Vit C) on two occasions [oral pill, 2g, 2x (baseline, during acute inflammation)].	Dietary supplement: Ascorbic Acid; All participants will receive ascorbic acid.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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.	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]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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]

Collaborators and Investigators

• Sponsor: University of Illinois at Chicago
• Investigators: Principal Investigator: Elizabeth Schroeder, MS, University of Illinois at Chicago

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 25, 2019
• Primary Completion (ACTUAL): March 13, 2020
• Study Completion (ACTUAL): March 13, 2020

Study Registration Dates

• First Submitted: March 20, 2019
• First Submitted That Met QC Criteria: March 21, 2019
• First Posted (ACTUAL): March 26, 2019

Study Record Updates

• Last Update Posted (ACTUAL): November 12, 2021
• Last Update Submitted That Met QC Criteria: October 15, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Endothelial Function; Oxidative Stress; Cardiorespiratory Fitness
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Immunologic Factors; Protective Agents; Micronutrients; Vitamins; Antioxidants; Vaccines; Ascorbic Acid
• Other Study ID Numbers: 2018-1550

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No