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

Sponsor
University of Illinois at Chicago (Other)
Overall Status
Terminated
CT.gov ID
NCT03889158
Collaborator
(none)
35
Enrollment
1
Location
2
Arms
11.6
Actual Duration (Months)
3
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or DiseaseIntervention/TreatmentPhase
  • Biological: Typhoid Vaccine
  • Dietary Supplement: Ascorbic Acid
Phase 4

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 Design

Study Type:
Interventional
Actual Enrollment :
35 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Intervention Model Description:
The vascular response to acute inflammation and oxidative stress is non-invasively assessed in individuals who are young with low fitness, older with low fitness, or older with high fitness.The vascular response to acute inflammation and oxidative stress is non-invasively assessed in individuals who are young with low fitness, older with low fitness, or older with high fitness.
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
Effect of Age and Fitness on Vascular Function and Oxidative Stress During Acute Inflammation
Actual Study Start Date :
Mar 25, 2019
Actual Primary Completion Date :
Mar 13, 2020
Actual Study Completion Date :
Mar 13, 2020

Arms and Interventions

ArmIntervention/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.

    Outcome Measures

    Primary Outcome Measures

    1. 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).

    2. 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

    1. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Integrative Physiology Laboratory, Suite 158ChicagoIllinoisUnited States60608

    Sponsors and Collaborators

    • University of Illinois at Chicago

    Investigators

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

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Elizabeth Schroeder, PhD Candidate, University of Illinois at Chicago
    ClinicalTrials.gov Identifier:
    NCT03889158
    Other Study ID Numbers:
    • 2018-1550
    First Posted:
    Mar 26, 2019
    Last Update Posted:
    Nov 12, 2021
    Last Verified:
    Oct 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Keywords provided by Elizabeth Schroeder, PhD Candidate, University of Illinois at Chicago
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment DetailDue to the impact of COVID-19 on study recruitment, we have insufficient data to break the older adults into fit and unfit groups. These groups were thus combined into a single "Older Adults" Group.
    Arm/Group TitleOlder AdultsYounger Adults
    Arm/Group DescriptionIndividuals 55-75 years of age.Individuals 18-35 years of age
    Period Title: Overall Study
    STARTED2015
    COMPLETED169
    NOT COMPLETED46

    Baseline Characteristics

    Arm/Group TitleOlder AdultsYounger AdultsTotal
    Arm/Group DescriptionIndividuals 55-75 years of ageIndividuals 18-35 years of ageTotal of all reporting groups
    Overall Participants16925
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    64
    (5)
    24
    (4)
    50
    (20)
    Sex: Female, Male (Count of Participants)
    Female
    3
    18.8%
    6
    66.7%
    9
    36%
    Male
    13
    81.3%
    3
    33.3%
    16
    64%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    2
    12.5%
    1
    11.1%
    3
    12%
    White
    13
    81.3%
    8
    88.9%
    21
    84%
    More than one race
    1
    6.3%
    0
    0%
    1
    4%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    16
    100%
    9
    100%
    25
    100%
    Flow-mediated dilation (% change in diameter) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [% change in diameter]
    3.5
    (1.9)
    6.3
    (3.3)
    4.5
    (2.8)
    Pulse wave velocity (m/s) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [m/s]
    8.8
    (2.1)
    5.6
    (.4)
    7.7
    (2.3)

    Outcome Measures

    1. Primary Outcome
    TitleChange in Endothelial Function
    DescriptionFlow-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 FrameVisit 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]

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleOlder AdultsYounger Adults
    Arm/Group DescriptionIndividuals 55-75 years of ageIndividuals 18-35 years of age
    Measure Participants169
    Baseline
    2.4
    (1.8)
    5.5
    (3.4)
    Baseline + Vit C
    3.4
    (2.7)
    5.7
    (3.0)
    Pre-Inflammation Baseline
    3.4
    (1.9)
    6.3
    (3.3)
    Inflammation
    1.6
    (1.7)
    5.8
    (3.4)
    Inflammation + Vit C
    2.8
    (1.9)
    6.1
    (3.2)
    2. Primary Outcome
    TitleChange in Oxidative Stress
    DescriptionOxidized 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.
    Time FrameVisit 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]

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleOlder AdultsYounger Adults
    Arm/Group DescriptionIndividuals 55-75 years of age.Individuals 18-35 years of age
    Measure Participants169
    Baseline
    6.2
    (1.2)
    4.7
    (2.1)
    Baseline + Vit C
    13.3
    (2.1)
    11.7
    (2.9)
    Pre-Inflammation
    5.8
    (1.1)
    5.4
    (1.2)
    Inflammation
    6.6
    (1.1)
    7.2
    (4.1)
    Inflammation + Vit C
    13.4
    (3.1)
    13.3
    (3.0)
    3. Secondary Outcome
    TitleChange in Arterial Stiffness
    DescriptionCentral 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.
    Time FrameVisit 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]

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleOlder AdultsYounger Adults
    Arm/Group DescriptionIndividuals 55-75 years of age.Individuals 18-35 years of age
    Measure Participants169
    Baseline
    9.3
    (2.0)
    5.8
    (.8)
    Baseline + Vit C
    9.9
    (3.0)
    5.9
    (.9)
    Pre-inflammation
    8.8
    (2.1)
    5.6
    (.4)
    Inflammation
    8.8
    (1.7)
    5.6
    (.6)
    Inflammation + Vit C
    8.9
    (2.1)
    5.7
    (.5)

    Adverse Events

    Time Frame1 month
    Adverse Event Reporting Description
    Arm/Group TitleOlder AdultsYounger Adults
    Arm/Group DescriptionIndividuals 55-75 years of ageIndividuals 18-35 years of age
    All Cause Mortality
    Older AdultsYounger Adults
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/16 (0%) 0/9 (0%)
    Serious Adverse Events
    Older AdultsYounger Adults
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/16 (0%) 0/9 (0%)
    Other (Not Including Serious) Adverse Events
    Older AdultsYounger Adults
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/16 (0%) 0/9 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleDr. Elizabeth Lefferts
    OrganizationUniversity of Illinois at Chicago
    Phone312-996-9607
    Emaileschro7@uic.edu
    Responsible Party:
    Elizabeth Schroeder, PhD Candidate, University of Illinois at Chicago
    ClinicalTrials.gov Identifier:
    NCT03889158
    Other Study ID Numbers:
    • 2018-1550
    First Posted:
    Mar 26, 2019
    Last Update Posted:
    Nov 12, 2021
    Last Verified:
    Oct 1, 2021