Aging, Skeletal Muscle, Vascular Endothelium
Conditions
Keywords
Reduced Activity, Muscular Atrophy, Vascular Dysfunction
Brief summary
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.
Interventions
BEHAVIORALStep Count Reduction
Subjects reduce daily step counts by approximately 70% through monitoring and recording from step-count monitor
Sponsors
University of Utah
National Center for Advancing Translational Sciences (NCATS)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brachial Artery Vascular Function | Baseline, during reduced activity (2 weeks) and 2 weeks post reduced activity (4 weeks) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Popliteal Artery Vascular Function | Baseline, during reduced activity (2 weeks) and 2 weeks post reduced activity (4 weeks) | 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. |
| Leg Microvascular Function | Baseline, during reduced activity (2 weeks) and 2 weeks post reduced activity (4 weeks) | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJoel D Trinity, Ph.D.
University of Utah
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Reduced Activity Reduction of daily step count by 70% for two weeks
Step Count Reduction: Subjects reduce daily step counts by approximately 70% through monitoring and recording from step-count monitor | 14 |
| Total | 14 |
Baseline characteristics
| Characteristic | Reduced Activity |
|---|---|
| Age, Continuous | 70 years STANDARD_DEVIATION 8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 14 |
| other Total, other adverse events | 0 / 14 |
| serious Total, serious adverse events | 0 / 14 |
Outcome results
Primary
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.
Time frame: Baseline, during reduced activity (2 weeks) and 2 weeks post reduced activity (4 weeks)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reduced Activity | Brachial Artery Vascular Function | Baseline FMD | 5.1 percent vasodilation | Standard Deviation 5.1 |
| Reduced Activity | Brachial Artery Vascular Function | During reduced activity | 3.1 percent vasodilation | Standard Deviation 2.4 |
| Reduced Activity | Brachial Artery Vascular Function | 2 week post reduced activity | 4.4 percent vasodilation | Standard Deviation 3.4 |
Secondary
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.
Time frame: Baseline, during reduced activity (2 weeks) and 2 weeks post reduced activity (4 weeks)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reduced Activity | Leg Microvascular Function | Baseline FMD | 385 ml/min | Standard Deviation 313 |
| Reduced Activity | Leg Microvascular Function | During reduced activity | 311 ml/min | Standard Deviation 202 |
| Reduced Activity | Leg Microvascular Function | 2 weeks post reduced activity | 412 ml/min | Standard Deviation 290 |
Secondary
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.
Time frame: Baseline, during reduced activity (2 weeks) and 2 weeks post reduced activity (4 weeks)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reduced Activity | Popliteal Artery Vascular Function | Baseline FMD | 4.5 percent vasodilation | Standard Deviation 4.5 |
| Reduced Activity | Popliteal Artery Vascular Function | During reduced activity | 2.4 percent vasodilation | Standard Deviation 2.1 |
| Reduced Activity | Popliteal Artery Vascular Function | 2 weeks post reduced activity | 3.6 percent vasodilation | Standard Deviation 2.3 |