Aging, Inflammation
Conditions
Keywords
Cardiorespiratory Fitness, Endothelial Function, Oxidative Stress
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.
Interventions
BIOLOGICALTyphoid Vaccine
All participants will receive the typhoid vaccine.
DIETARY_SUPPLEMENTAscorbic Acid
All participants will receive ascorbic acid.
Sponsors
University of Illinois at Chicago
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Pre-assignment details
Due 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.
Participants by arm
| Arm | Count |
|---|---|
| Older Adults Individuals 55-75 years of age | 16 |
| Younger Adults Individuals 18-35 years of age | 9 |
| Total | 25 |
Baseline characteristics
| Characteristic | Younger Adults | Total | Older Adults |
|---|---|---|---|
| Age, Continuous | 24 years STANDARD_DEVIATION 4 | 50 years STANDARD_DEVIATION 20 | 64 years STANDARD_DEVIATION 5 |
| Flow-mediated dilation | 6.3 % change in diameter STANDARD_DEVIATION 3.3 | 4.5 % change in diameter STANDARD_DEVIATION 2.8 | 3.5 % change in diameter STANDARD_DEVIATION 1.9 |
| Pulse wave velocity | 5.6 m/s STANDARD_DEVIATION 0.4 | 7.7 m/s STANDARD_DEVIATION 2.3 | 8.8 m/s STANDARD_DEVIATION 2.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 21 Participants | 13 Participants |
| Region of Enrollment United States | 9 participants | 25 participants | 16 participants |
| Sex: Female, Male Female | 6 Participants | 9 Participants | 3 Participants |
| Sex: Female, Male Male | 3 Participants | 16 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 9 |
| other Total, other adverse events | 0 / 16 | 0 / 9 |
| serious Total, serious adverse events | 0 / 16 | 0 / 9 |
Outcome results
Primary
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]
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Older Adults | Change in Endothelial Function | Baseline + Vit C | 3.4 % change in diameter | Standard Deviation 2.7 |
| Older Adults | Change in Endothelial Function | Inflammation | 1.6 % change in diameter | Standard Deviation 1.7 |
| Older Adults | Change in Endothelial Function | Pre-Inflammation Baseline | 3.4 % change in diameter | Standard Deviation 1.9 |
| Older Adults | Change in Endothelial Function | Inflammation + Vit C | 2.8 % change in diameter | Standard Deviation 1.9 |
| Older Adults | Change in Endothelial Function | Baseline | 2.4 % change in diameter | Standard Deviation 1.8 |
| Younger Adults | Change in Endothelial Function | Inflammation + Vit C | 6.1 % change in diameter | Standard Deviation 3.2 |
| Younger Adults | Change in Endothelial Function | Baseline | 5.5 % change in diameter | Standard Deviation 3.4 |
| Younger Adults | Change in Endothelial Function | Baseline + Vit C | 5.7 % change in diameter | Standard Deviation 3 |
| Younger Adults | Change in Endothelial Function | Pre-Inflammation Baseline | 6.3 % change in diameter | Standard Deviation 3.3 |
| Younger Adults | Change in Endothelial Function | Inflammation | 5.8 % change in diameter | Standard Deviation 3.4 |
Primary
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.
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]
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Older Adults | Change in Oxidative Stress | Baseline + Vit C | 13.3 ug/mL | Standard Deviation 2.1 |
| Older Adults | Change in Oxidative Stress | Inflammation | 6.6 ug/mL | Standard Deviation 1.1 |
| Older Adults | Change in Oxidative Stress | Pre-Inflammation | 5.8 ug/mL | Standard Deviation 1.1 |
| Older Adults | Change in Oxidative Stress | Inflammation + Vit C | 13.4 ug/mL | Standard Deviation 3.1 |
| Older Adults | Change in Oxidative Stress | Baseline | 6.2 ug/mL | Standard Deviation 1.2 |
| Younger Adults | Change in Oxidative Stress | Inflammation + Vit C | 13.3 ug/mL | Standard Deviation 3 |
| Younger Adults | Change in Oxidative Stress | Baseline | 4.7 ug/mL | Standard Deviation 2.1 |
| Younger Adults | Change in Oxidative Stress | Baseline + Vit C | 11.7 ug/mL | Standard Deviation 2.9 |
| Younger Adults | Change in Oxidative Stress | Pre-Inflammation | 5.4 ug/mL | Standard Deviation 1.2 |
| Younger Adults | Change in Oxidative Stress | Inflammation | 7.2 ug/mL | Standard Deviation 4.1 |
Secondary
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.
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]
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Older Adults | Change in Arterial Stiffness | Baseline | 9.3 m/s | Standard Deviation 2 |
| Older Adults | Change in Arterial Stiffness | Inflammation | 8.8 m/s | Standard Deviation 1.7 |
| Older Adults | Change in Arterial Stiffness | Pre-inflammation | 8.8 m/s | Standard Deviation 2.1 |
| Older Adults | Change in Arterial Stiffness | Inflammation + Vit C | 8.9 m/s | Standard Deviation 2.1 |
| Older Adults | Change in Arterial Stiffness | Baseline + Vit C | 9.9 m/s | Standard Deviation 3 |
| Younger Adults | Change in Arterial Stiffness | Inflammation + Vit C | 5.7 m/s | Standard Deviation 0.5 |
| Younger Adults | Change in Arterial Stiffness | Baseline + Vit C | 5.9 m/s | Standard Deviation 0.9 |
| Younger Adults | Change in Arterial Stiffness | Baseline | 5.8 m/s | Standard Deviation 0.8 |
| Younger Adults | Change in Arterial Stiffness | Pre-inflammation | 5.6 m/s | Standard Deviation 0.4 |
| Younger Adults | Change in Arterial Stiffness | Inflammation | 5.6 m/s | Standard Deviation 0.6 |