Vascular Dysfunction During Physical Inactivity

Vascular Dysfunction During Physical Inactivity: Role of Oxidative Stress

Prolonged periods of reduced activity are associated with decreased vascular function and muscle atrophy. Physical inactivity due to a sedentary lifestyle or acute hospitalization is also associated with impaired recovery, hospital readmission, and increased mortality. Older adults are a particularly vulnerable population as functional (vascular and skeletal muscle mitochondrial dysfunction) and structural deficits (loss in muscle mass leading to a reduction in strength) are a consequence of the aging process. The combination of inactivity and aging poses an added health threat to these individuals by accelerating the negative impact on vascular and skeletal muscle function and dysfunction. The underlying factors leading to vascular and skeletal muscle dysfunction are unknown, but have been linked to increases in oxidative stress. Additionally, there is a lack of understanding of how vascular function is impacted by inactivity in humans and how these changes are related to skeletal muscle function. It is the goal of this study to investigate the mechanisms that contribute to disuse muscle atrophy and vascular dysfunction in order to diminish their negative impact, and preserve vascular and skeletal muscle function.

Study Overview

• Status: Completed
• Conditions: Aging; Skeletal Muscle; Vascular Endothelium
• Intervention / Treatment: Behavioral: Step Count Reduction

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84148
      • VA Medical Center Building

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Individuals who have recently undergone surgery or injury requiring inactivity

Exclusion Criteria:

• Cardiac abnormalities considered exclusionary by the study physician (congestive heart failure, coronary artery disease, right-to-left shunt)
• Uncontrolled endocrine or metabolic disease
• Glomerular filtration rate < 45 mL/min/1.73 m^2 or evidence of kidney disease or failure
• Vascular disease or risk factors of peripheral atherosclerosis
• Risk of deep vein thrombosis including family history of thrombophilia, pulmonary emboli, deep vein thrombosis
• Use of anticoagulant therapy
• Elevated systolic pressure > 180 or a diastolic blood pressure > 110
• Implanted electronic devices such as pacemakers, infusion pumps, stimulators
• Cancer or history of successfully treated cancer (less than 1 year) other than basal cell carcinoma
• Currently on a weight-loss diet or body mass index > 35 kg/m^2
• Inability to abstain from smoking for duration of study
• History of > 20 pack per year smoking
• Positive for human immunodeficiency virus, hepatitis B or hepatitis C
• Recent anabolic or corticosteroids use (within 3 months)
• Subjects with hemoglobin or hematocrit lower than accepted lab values
• Agitation/aggression disorder
• History of stroke with motor disability
• Recent history (< 12 months) of gastrointestinal bleed
• Depression diagnosis
• Alcohol or drug abuse
• Liver disease (AST/ALT 2 times above the normal limit, hyperbilirubinemia)
• Respiratory disease (acute upper respiratory infection, history of chronic lung disease with resting oxygen saturation < 97% on room air)
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Reduced Activity; Reduction of daily step count by 70% for two weeks, followed by two week recovery to normal activity level	Behavioral: Step Count Reduction; Subjects reduce daily step counts by approximately 70% through monitoring and recording from step-count monitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brachial Artery Vascular Function	The flow rate of brachial artery measured by flow-mediated dilation (FDM). Doppler ultrasound will be used to determine brachial artery vascular function. Specifically, this assessment will include the measurement of flow rate and artery diameter at rest and in response to flow mediated dilation.	Baseline, during reduced activity (2 weeks) and 2 weeks post reduced activity (4 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Popliteal Artery Vascular Function	Flow rate of popliteal artery measured by flow-mediated dilation (FMD). Doppler ultrasound will be used to determine popliteal artery vascular function. Specifically, this assessment will include the measurement of flow rate and artery diameter at rest and in response to flow mediated dilation.	Baseline, during reduced activity (2 weeks) and 2 weeks post reduced activity (4 weeks)
Leg Microvascular Function	Flow rate of leg microvasculature assessed by passive leg movement (PLM). Doppler ultrasound will be used to determine leg microvasculature function. Specifically, this assessment will include the measurement of flow rate at rest and in response to movement.	Baseline, during reduced activity (2 weeks) and 2 weeks post reduced activity (4 weeks)

Collaborators and Investigators

• Sponsor: University of Utah
• Collaborators: University of Utah Center for Clinical and Translational Science (CCTS)
• Investigators: Principal Investigator: Joel D Trinity, Ph.D., University of Utah

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2019
• Primary Completion (Actual): March 31, 2021
• Study Completion (Actual): March 31, 2021

Study Registration Dates

• First Submitted: April 29, 2021
• First Submitted That Met QC Criteria: April 29, 2021
• First Posted (Actual): May 5, 2021

Study Record Updates

• Last Update Posted (Actual): February 16, 2024
• Last Update Submitted That Met QC Criteria: June 26, 2023
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Muscular Atrophy; Vascular Dysfunction; Reduced Activity
• Other Study ID Numbers: IRB #111321

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: No
• Studies a U.S. FDA-regulated device product: No