Project 4B: Lower Extremity Strength Training in ICU Patients

Not Applicable

Completed

• Conditions: Sepsis
• Interventions: Device: Muscle stimulation with Niveus medical stimulator; Device: measurement of maximal isometric twitch strength; Procedure: Muscle Biopsy; Device: ineffective muscle stimulation; Other: Blood and Urine Sampling

• Registration Number: NCT02467023
• Lead Sponsor: University of Florida

Brief Summary

The purpose of this research study is to see if electrical stimulation of the leg muscles will improve strength in patients receiving mechanical ventilation in the intensive care unit (ICU). ICU care frequently results in chronically critically ill (CCI) patients. Some CCI patients develop persistent inflammation/immunosuppression and catabolism syndrome (PICS), and they have morbid long-term outcomes. CCI patients with PICS often develop severe limb muscle atrophy, weakness and accelerated protein catabolism. Limb muscle dysfunction in PICS is due to many factors including sepsis/inflammation, proteolysis, apoptosis, and inactivity. Despite the seriousness of limb muscle weakness in CCI patients receiving mechanical ventilation, little is known about exercise strategies to treat this problem. There is limited knowledge about how strength training impacts inflammation and catabolism in CCI patients. In addition, an assessment of the effect of exercise on markers of inflammation and protein catabolism on muscle samples obtained with biopsy techniques and venous blood samples will be performed. This project will further understanding of how treating CCI-related muscle weakness with strength training cannot only improve muscle function, but also potentially blunt the inflammation and catabolism of PICS.

Detailed Description

As a participant in the study, the following will take place: Assignment to study groups: a random assignment will be done to one of two groups by a list generated by a computer program, much like flipping a coin. One group of subjects will be assigned to an effective muscle stimulation group and the second group will be assigned to a group that will receive ineffective stimulation (Control or Sham). Muscle stimulation will be performed with a Niveus medical stimulator on both quadriceps muscle groups for 30 minutes, five days per week. The stimulator will be individually adjusted in terms of intensity of stimulation to elicit a visible or palpable quadriceps muscle contraction. Four contractions per minute will be performed for a total of approximately 120 contractions per 30 minute treatment. Isometric Muscle strength testing: All subjects will undergo isometric muscle strength testing. Maximal isometric twitch strength will be measured by placing the subjects' dominant leg in a frame that will hold the knee at 60°. A cuff will be placed around the patient's ankle and will be connected to an electronic dynamometer with the cable. A magnetic nerve stimulator will be used over the body of the quadriceps muscle to stimulate the muscle.

Study Timeline

• Study First Submitted: 2015-05-19
• Study First Submitted QC: 2015-06-04
• Study First Posted: 2015-06-09
• Study Start: 2015-09
• Primary Completion: 2016-07-07
• Study Completion: 2016-07-15
• Status Verified: 2018-01
• Last Update Submitted: 2018-01-17
• Last Update Posted: 2018-01-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 5

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ineffective muscle stimulation group	ineffective muscle stimulation	Subjects assigned to this arm will be studied for up to 28 days or until discharge and will receive a sham muscle stimulation with Niveus medical stimulator, multiple measurement of maximal isometric twitch strength blood and urine samples, and a muscle biopsy sample with muscle biopsy medication fentanyl, muscle biopsy medication versed, and muscle biopsy medication lidocaine.
effective muscle stimulation group	Muscle stimulation with Niveus medical stimulator	Subjects in this arm will be in the study for up to 28 days or until discharge from the ICU. They will receive lower extremity muscle stimulation with Niveus medical stimulator, multiple measurement of maximal isometric twitch strength, muscle biopsy with muscle biopsy medication fentanyl, muscle biopsy medication versed, muscle biopsy medication lidocaine, and blood and urine sampling.
effective muscle stimulation group	Blood and Urine Sampling	Subjects in this arm will be in the study for up to 28 days or until discharge from the ICU. They will receive lower extremity muscle stimulation with Niveus medical stimulator, multiple measurement of maximal isometric twitch strength, muscle biopsy with muscle biopsy medication fentanyl, muscle biopsy medication versed, muscle biopsy medication lidocaine, and blood and urine sampling.
ineffective muscle stimulation group	measurement of maximal isometric twitch strength	Subjects assigned to this arm will be studied for up to 28 days or until discharge and will receive a sham muscle stimulation with Niveus medical stimulator, multiple measurement of maximal isometric twitch strength blood and urine samples, and a muscle biopsy sample with muscle biopsy medication fentanyl, muscle biopsy medication versed, and muscle biopsy medication lidocaine.
effective muscle stimulation group	measurement of maximal isometric twitch strength	Subjects in this arm will be in the study for up to 28 days or until discharge from the ICU. They will receive lower extremity muscle stimulation with Niveus medical stimulator, multiple measurement of maximal isometric twitch strength, muscle biopsy with muscle biopsy medication fentanyl, muscle biopsy medication versed, muscle biopsy medication lidocaine, and blood and urine sampling.
effective muscle stimulation group	Muscle Biopsy	Subjects in this arm will be in the study for up to 28 days or until discharge from the ICU. They will receive lower extremity muscle stimulation with Niveus medical stimulator, multiple measurement of maximal isometric twitch strength, muscle biopsy with muscle biopsy medication fentanyl, muscle biopsy medication versed, muscle biopsy medication lidocaine, and blood and urine sampling.
ineffective muscle stimulation group	Muscle Biopsy	Subjects assigned to this arm will be studied for up to 28 days or until discharge and will receive a sham muscle stimulation with Niveus medical stimulator, multiple measurement of maximal isometric twitch strength blood and urine samples, and a muscle biopsy sample with muscle biopsy medication fentanyl, muscle biopsy medication versed, and muscle biopsy medication lidocaine.
ineffective muscle stimulation group	Blood and Urine Sampling	Subjects assigned to this arm will be studied for up to 28 days or until discharge and will receive a sham muscle stimulation with Niveus medical stimulator, multiple measurement of maximal isometric twitch strength blood and urine samples, and a muscle biopsy sample with muscle biopsy medication fentanyl, muscle biopsy medication versed, and muscle biopsy medication lidocaine.

Primary Outcome Measures

Name	Time	Method
Isometric muscle twitch force measured at the start of the study, approximately every seven days thereafter and final day of study.	Change from days 1, 7, 14, 21, and 28	Measurement of maximal isometric strength will be done by using a dynamometer.
Change in inflammatory markers on days 1, 7, 14, 21, and 28.	Change from days 1, 7, 14, 21, and 28	blood and urine will be tested for the markers of inflammation. The following will be tested: (IL)-1β, IL-6, IL-8, IL-10, IL-12, (TNF)α, (IFN)γ, (MCP)-1, (IP)10, (SDF)-1, (MIP)1α, (HMG)B1, procalcitonin, and (CRP).
Change in immunosuppressive markers on days 1, 7, 14, 21, and 28.	Change from days 1, 7, 14, 21, and 28	blood and urine will be tested for the markers of immunosuppression. The following will be tested: MDSC phenotype (HLA-DRlow)

Secondary Outcome Measures

Name	Time	Method
Measurement of key proteins of mitochondrial function using immunohistochemistry and Western blotting	Measurement on day 28	Quadriceps muscle samples will be obtained with percutaneous biopsies following training. Muscle fiber cross-sectional area, myosin heavy chain composition, and changes in atrophy-specific proteins will be assessed using immunohistochemistry and Western blotting, respectively. High-resolution respirometry on permeabilized muscle fibers will be used to measure changes in mitochondrial O2 consumption and muscle bioenergetics. In addition, we will measure key proteins of mitochondrial function and biogenesis.

Trial Locations

Locations (1)

UF Health Shands Hospital at the University of Florida; 🇺🇸 Gainesville, Florida, United States