Blood Flow Restriction Exercise for Those With SCI

NCT04889092 | Completed DMC

• 2 other identifiers: B3562-R1IO1RX003562-01A1
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Spinal cord injuries (SCI) are among the most debilitating conditions an individual can sustain with the estimates of SCI incidence in the United States at 12,000 new cases per year. The loss of innervation to the tissues muscle below the level of the lesion results in reduced physical activity which leads to an array of secondary complications including muscle atrophy, cardiovascular and metabolic disease, obesity and vascular dysfunction. This further leads to exercise intolerance, reduced quality of life and depression. Although current rehabilitative programs focus on improving muscle strength in this population, the efficacy of these programs is challenged by the injury related motor impairment, which limits the exercise intensity and subsequent positive muscular adaptations. Therefore, development of an exercise program that promotes maximal muscular adaptations to light intensity exercise could greatly improve the efficacy of rehabilitation in the SCI population and help restore functional capacity and quality of life for these individuals. Blood flow restriction (BFR) exercise has shown tremendous promise for improving muscle size and strength in a variety of healthy and clinical populations, however the benefits of BFR exercise for those with SCI has not been established. Thus, the purpose of this Merit proposal is to conduct a comprehensive study that explores the benefits and risks of BFR exercise in the incomplete SCI population. In general individuals with chronic incomplete SCI will be recruited to partake in two 8-week training periods (20 sessions) that involve traditional knee extension/flexion exercise or knee extension/flexion exercise with blood flow restriction. There will be a series of measurements before and after the 8-week intervention to look at changes in muscle and vascular function. Specific Aim 1 will determine how the 8-weeks of BFR exercise influenced muscle strength (Biodex isokinetic dynamometer), muscle cross sectional area and volume (CTscan) and fatigue resistance. Specific Aim 2 will determine how this novel 8-week training intervention impacts peripheral vascular function. Specifically, changes in nitric oxide mediated endothelial function will be determined through tests of flow mediated dilation, changes in endothelial function of the microvascular network will be determined through assessments of reactive hyperemia and changes in arterial stiffness will be determined through measurements of pulse wave velocity. Specific Aim 3 will focus on the safety of BFR exercise for the SCI population. Those with SCI are at greater risk for thrombosis and DVT compared to able bodied individuals. Although unlikely, the introduction of temporary blood stasis during BFR exercise might augment this risk. Thus, the third aim of this study will be to determine changes in innate immune activation and thrombosis risk. Specifically, blood will be collected at multiple timepoints throughout the training intervention and analyzed for hypoxia-inducible factor 1-alpha, neutrophil extra cellular traps (which act as prothrombotic scaffolds), neutrophil-platelet aggregates and inflammatory cytokines. Ultimately, if the improvements in muscle and vascular function following BFR resistance exercise is greater than the traditional resistance exercise often performed in rehabilitation settings, without increasing risk for DVT, it should be incorporated into the long-term rehabilitation programs for Veterans with SCI.

Conditions

Spinal Cord Injury

Keywords

blood flow; functional performance; cytokines; exercise; skeletal muscle

Outcome Measures

Primary Outcomes (8)

• Change in muscle cross sectional area

  CTscan will be used to quantify cross sectional areal of several knee extensor and flexor muscles.

  0 and 56 days

• Change in muscle strength

  Using a biodex dynamometer we will quantify maximal knee extension strength and fatigue resistance.

  0 and 56 days

• Change in vascular endothelial function

  Flow mediated dilation (FMD)will be used to determine endothelial function in the popliteal arteries.

  0 and 56 days

• Change in D-dimer

  Blood will be sampled and analyzed for D-dimer, a marker of coagulation.

  0, 1, 28 and 56 days

• Change in muscle fatigue resistance (percent decrease in maximal voluntary torque following fatigue protocol)

  A fatigue knee extension protocol on a Biodex system 3 dynamometer will be used to quantify fatigue resistance of the quadriceps muscle group. Subjects will perform a maximal voluntary contraction before and after a 5 minute knee extension fatigue protocol. The relative decrease in maximal voluntary torque produced as a result of the fatiguing protocol (% decrease in torque) will provide an indication of fatigue resistance.

  0 and 56 days

• Change in muscle volume

  CTscan will be used to image the thigh from knee to pelvic. Muscle volume will be measured for several knee extensor and knee flexor muscles.

  0 and 56 days

• Change in thrombin / antithrombin complex

  Blood samples will be used for analysis of thrombin / antithrombin complex, a blood marker of coagulation.

  0, 1, 28 and 56 days

• Change in prothrombin fragment 1.2

  Blood samples will be used for analysis of prothrombin fragment 1.2, a marker of coagulation.

  0, 1, 28 and 56 days

Secondary Outcomes (10)

• Change in vessel stiffness

  0 and 56 days

• Change in interleukin (IL)-Beta

  0, 1, 28 and 56 days

• Change in neutrophil-platelet aggregates

  0, 1, 28 and 56 days

• Change in Hypoxia-inducible factor 1-alpha (HIF-1 )

  0, 1, 28 and 56 days

• Change in vascular endothelial growth factor (VEGF)

  0, 1, 28 and 56 days

Study Arms (2)

blood flow restriction exercise

EXPERIMENTAL

8 weeks (20 sessions) of blood flow restriction knee extension/flexion exercise

Other: Blood Flow Restriction exercise

traditional resistance exercise

ACTIVE COMPARATOR

8 weeks (20 sessions) of traditional knee extension/flexion resistance exercise

Other: Traditional resistance exercise

Interventions

Blood Flow Restriction exercise OTHER

Exercise training will consist of blood flow restriction exercise. Specifically blood pressure cuff will be wrapped around the most proximal portion of the thigh and inflated to a pressure that is 80% of the pressure required to completely occlude femoral blood flow. With the cuff inflated the subject will perform a series of knee extension/flexion exercise protocol. This consists of 30 reps, 15 reps, 15 reps and 15 reps all separated by 1 minute of recovery. All reps will be performed at 30% of the subjects 1 repetition max. This will be preformed 20 times over 8 weeks.

Also known as: BFR

blood flow restriction exercise

Traditional resistance exercise OTHER

Traditional knee extension/flexion exercise will be performed. This will consist of a series of 13 reps, 12 reps, 12 reps with 1 minute recovery between each set. The resistance will be set at 60% of their 1 repetition max. This will be performed 20 times across 8 weeks.

Also known as: resistance exercise

traditional resistance exercise

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All participants must be between the ages of 18 and 75 years and have a medically stable incomplete spinal cord injury (AIS C or D) at least 1-year post injury
• As the aim of this investigation is to focus on muscular and vascular adaptations to BFR exercise in the lower limbs, the level of injury must be between C3-L1

You may not qualify if:

• Females that are pregnant
• Individuals required to have ventilator assist devices
• Individuals with significant active systemic disease, e.g. heart disease, renal failure/insufficiency and uncontrolled diabetes, uncontrolled hypertension and blood disorders that increase the risk for clot formation.
• Individuals with chronic inflammatory disease states (i.e. multiple sclerosis or rheumatoid arthritis, Guillen-Barre syndrome, chronic inflammatory demyelinating disorder and acute amyotrophic lateral sclerosis)
• Obese patients (\>30% body fat based on skinfold measurements)
• History of repeated DVTs or a DVT within the last year.
• Individuals currently taking vasodilators
• Individuals with orthopaedic limitations that would prevent them from performing knee extension/flexion exercise (with the exception of decreased strength due to the SCI)
• Individuals with uncontrolled spasticity or a history of frequent autonomic dysreflexia

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Louis Stokes VA Medical Center, Cleveland, OH

Cleveland, Ohio, 44106-1702, United States

Location

MeSH Terms

Conditions

Spinal Cord Injuries; Motor Activity

Interventions

Blood Flow Restriction Therapy; Resistance Training

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Behavior

Intervention Hierarchy (Ancestors)

Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities; Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• John McDaniel, PhD

  Louis Stokes VA Medical Center, Cleveland, OH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Some of the variables will be masked by the outcome assessor as they will not be present during data collection. Other variables will not be masked due to nature of data collection.
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: This is a crossover model in which subjects will be assigned the blood flow restriction exercise or control condition (standard exercise) in random order. Data will be collected pre, during and at the end of each 8-week exercise intervention. The order of conditions will be randomly assigned.

Study Record Dates

• First Submitted: May 11, 2021
• First Posted: May 17, 2021
• Study Start: July 1, 2021
• Primary Completion: August 31, 2024
• Study Completion: August 31, 2024
• Last Updated: September 27, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)