Targeting Oxidative Stress to Prevent Vascular and Skeletal Muscle Dysfunction During Disuse

NCT04351113 | Active Not Recruiting DMC

• 2 other identifiers: IRB_001113211R01HL142603-01A1
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 1

Brief Summary

Prolonged periods of reduced activity are associated with decreased vascular function and muscle atrophy. Physical inactivity due to 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 our goal 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 across all the lifespan.

Conditions

Aging; Oxidative Stress; Vascular Endothelium; Skeletal Muscle; Antioxidants

Keywords

Aging; cardiovascular degeneration; Muscular atrophy

Outcome Measures

Primary Outcomes (2)

• Change in blood vessel diameter after PLM

  10 days

• Change in blood vessel flow rate after PLM

  10 days

Secondary Outcomes (6)

• Change in O2 augmented maximal mitochondrial oxidative capacity (Vmax) after plantar flexion

  10 days

• Change in phosphocreatinine concentration [PCr] after plantar flexion

  10 days

• Change in inorganic phosphate concentration [Pi] after plantar flexion

  10 days

• Change in adenosine triphosphate (ATP) concentration after plantar flexion

  10 days

• Change in muscle mass as measured in kilograms by dual-energy X-ray absorptiometry (DXA) after bed rest.

  10 days

Study Arms (3)

MITO-AO

EXPERIMENTAL

Healthy older adult subjects ages 65-75 will take the supplement MITO-AO during a 5 day bed rest and will be assessed for vascular function independent of metabolism with passive leg movement (PLM), skeletal muscle bioenergetics independent of vascular constraints (i.e. blood flow and O2 supply) with phosphorous magnetic resonance spectroscopy (31P-MRS), and skeletal muscle bioenergetics under normal blood flow and O2 supply.

Dietary Supplement: MITO-AO; Other: Passive Leg Movement (PLM); Other: Plantar flexion; Other: Isometric knee extensor test; Other: Bed rest

PB-125

EXPERIMENTAL

Healthy older adult subjects ages 65-75 will take the supplement PB-125 during a 5 day bed rest and will be assessed for vascular function independent of metabolism with passive leg movement (PLM), skeletal muscle bioenergetics independent of vascular constraints (i.e. blood flow and O2 supply) with phosphorous magnetic resonance spectroscopy (P-MRS), and skeletal muscle bioenergetics under normal blood flow and O2 supply.

Dietary Supplement: PB-125; Other: Passive Leg Movement (PLM); Other: Plantar flexion; Other: Isometric knee extensor test; Other: Bed rest

Placebo

PLACEBO COMPARATOR

Healthy older adult subjects ages 65-75 will take placebo during a 5 day bed rest and will be assessed for vascular function independent of metabolism with passive leg movement (PLM), skeletal muscle bioenergetics independent of vascular constraints (i.e. blood flow and O2 supply) with phosphorous magnetic resonance spectroscopy (P-MRS), and skeletal muscle bioenergetics under normal blood flow and O2 supply.

Other: Placebo; Other: Passive Leg Movement (PLM); Other: Plantar flexion; Other: Isometric knee extensor test; Other: Bed rest

Interventions

MITO-AO DIETARY_SUPPLEMENT

Participants will receive 160 mg with breakfast on day 1 of bed rest and 40 mg with breakfast on days 2-5.

MITO-AO

PB-125 DIETARY_SUPPLEMENT

Participants will receive 100 mg on days 1-5 of bed rest.

PB-125

Placebo OTHER

Participants will receive Placebo on days 1-5 of bed rest.

Placebo

Passive Leg Movement (PLM) OTHER

Participants will be tested for passive leg movement on baseline day 1, bed rest day 1, and post bed rest.

MITO-AO; PB-125; Placebo

Plantar flexion OTHER

Participants will undergo plantar flexion on baseline day 2, pre bed rest, and post bed rest.

MITO-AO; PB-125; Placebo

Isometric knee extensor test OTHER

Participants will undergo isometric knee extension on baseline day 2, pre bed rest, and post bed rest.

MITO-AO; PB-125; Placebo

Bed rest OTHER

Participants will undergo 5 days bed rest after 5 day baseline assessments

MITO-AO; PB-125; Placebo

Eligibility Criteria

• Age: 65 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Age between 65-85 yrs
• Ability to sign informed consent
• Montreal cognitive assessment (MOCA) exam score greater-than or equal to 26 4. Free-living, prior to admission

You may not qualify if:

• Uncontrolled endocrine or metabolic disease (e.g., hypo/hyperthyroidism, diabetes)
• Glomerular filtration rate (GFR) less-than 30 mL/min/1.73m2 or evidence of kidney disease or failure
• Vascular disease or risk factors of peripheral atherosclerosis. (e.g., uncontrolled hypertension, obesity, diabetes, hypercholesterolemia greater-than 250 mg/dl, claudication or evidence of venous or arterial insufficiency upon palpitation of femoral, popliteal and pedal arteries)
• Risk of deep vein thrombosis (DVT) including family history of thrombophilia, DVT, pulmonary emboli, myeloproliferative diseases including polycythemia (Hb greater-than 18 g/dL) or thrombocytosis (platelets greater-than 400x103/mL), and connective tissue diseases (positive lupus anticoagulant), hyperhomocysteinemia, deficiencies of factor V Leiden, proteins S and C, and antithrombin III
• Use of anticoagulant therapy (e.g., Coumadin, heparin)
• Elevated systolic pressure greater-than 150 or a diastolic blood pressure greater-than 100 (treated or untreated)
• Implanted electronic devices (e.g., pacemakers, electronic infusion pumps, stimulators)
• Cancer or history of successfully treated cancer (less than 1 year) other than basal cell carcinoma
• Inability to abstain from smoking for duration of study
• A history of greater-than 20 pack per year smoking
• HIV or hepatitis B or C\*
• Recent anabolic or corticosteroids use (within 3 months)
• Subjects with hemoglobin or hematocrit lower than accepted lab values
• Agitation/aggression disorder (by psychiatric history and exam)
• History of stroke with motor disability

Sponsors & Collaborators

• Joel Trinity: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

VA Medical Center

Salt Lake City, Utah, 84148, United States

Location

MeSH Terms

Conditions

Muscular Atrophy

Interventions

Bed Rest

Condition Hierarchy (Ancestors)

Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double blind placebo controlled design
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Research Assistant Professor

Model Details: Randomized double blind parallel 3 group study

Study Record Dates

• First Submitted: April 14, 2020
• First Posted: April 17, 2020
• Study Start: September 1, 2019
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: April 30, 2026

Record last verified: 2026-04

Locations

US (1)