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)
• Enrollment: 35
• Location: 1
• Arms: 2
• Actual Duration (Months): 11.6
• Patients Per Site Per Month: 3

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 Disease	Intervention/Treatment	Phase
Aging; Inflammation	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

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.

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

	Site	City	State	Country	Postal Code
1	Integrative Physiology Laboratory, Suite 158	Chicago	Illinois	United States	60608

Sponsors and Collaborators

• University of Illinois at Chicago

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 5, 2019

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: Cardiorespiratory Fitness; Endothelial Function; Oxidative Stress
• Additional relevant MeSH terms: Inflammation; Ascorbic Acid; Vaccines

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Older Adults	Younger Adults
Arm/Group Description	Individuals 55-75 years of age.	Individuals 18-35 years of age
Period Title: Overall Study
STARTED	20	15
COMPLETED	16	9
NOT COMPLETED	4	6

Baseline Characteristics

Arm/Group Title	Older Adults	Younger Adults	Total
Arm/Group Description	Individuals 55-75 years of age	Individuals 18-35 years of age	Total of all reporting groups
Overall Participants	16	9	25
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

Title	Change in Endothelial Function
Description	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]

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Older Adults	Younger Adults
Arm/Group Description	Individuals 55-75 years of age	Individuals 18-35 years of age
Measure Participants	16	9
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

Title	Change in Oxidative Stress
Description	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]

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Older Adults	Younger Adults
Arm/Group Description	Individuals 55-75 years of age.	Individuals 18-35 years of age
Measure Participants	16	9
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

Title	Change in Arterial Stiffness
Description	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]

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Older Adults	Younger Adults
Arm/Group Description	Individuals 55-75 years of age.	Individuals 18-35 years of age
Measure Participants	16	9
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 Frame	1 month
Arm/Group Title	Older Adults		Younger Adults
Arm/Group Description	Individuals 55-75 years of age		Individuals 18-35 years of age
All Cause Mortality
	Older Adults		Younger Adults
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/9 (0%)
Serious Adverse Events
	Older Adults		Younger Adults
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Older Adults		Younger Adults
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (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.