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

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

Interventions

DIETARY_SUPPLEMENT

MITO-AO

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

DIETARY_SUPPLEMENT

PB-125

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

OTHER

Placebo

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

OTHER

Passive Leg Movement (PLM)

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

OTHER

Plantar flexion

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

OTHER

Isometric knee extensor test

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

OTHER

Bed rest

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

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)

  collaborator NIH

• Joel Trinity

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

65 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2019-09-01

Primary Completion

2026-06-30

Completion

2026-06-30

Countries

• United States

Study Locations