Clinical trial NCT02467023: Project 4B: Lower Extremity Strength Training in ICU Patients
Official title: Persistent Inflammation, Immunosuppression and Catabolism Syndrome (PICS): A New Horizon for Surgical Critical Care: Project 4B: Lower Extremity Strength Training in ICU Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sepsis
Keywords: chronic critical illness
strength training
exercise
sepsis
mechanical ventilation
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of General Medical Sciences (NIGMS)
First posted: 2015-06-09
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion criteria

1. Presence in the surgery or trauma ICU,
2. age of ≥18 years,
3. received MV for 3 day and expected to survive ICU stay,
4. ability to obtain informed consent from patient or legally authorized representative,
5. approval of an ICU attending for patient to participate.

Exclusion criteria

1. Have an uncontrollable source of sepsis (e.g., irreversible disease state, unresectable dead bowel),
2. are receiving "comfort care" or have advanced care directives limiting resuscitative efforts,
3. have an implanted electronic device (pacemaker/defibrillator/insulin pump, etc.)
4. have known HIV infection with CD4 count \< 200 cells/mm3,
5. are organ transplant recipients on immunosuppressive agent(s),
6. have a known pregnancy,
7. history of stroke with weakness,
8. Inability to walk without assistance prior to ICU admission (excluding the use of cane or walker)
9. lower-extremity amputations, rheumatic or severe osteoarthritis of any joint in the lower extremity,
10. Unrepaired hip fracture, unstable cervical spine or other bone diseases
11. arterial or venous insufficiency in the lower extremity,
12. have prior arrangements to be transferred to other facilities before 28 days of treatment,
13. have an unstable or "difficult airway" at 14 days of ICU care, predicted to last for more than 72 hours,
14. are on vasopressor or vasodilatory agents as a continuous infusion at more than a "renal dose,"
15. have severe cardiac dysrhythmias,
16. have acute coronary syndrome,
17. have pulmonary contraindications (pneumo/hemothorax, flail chest),
18. have persistent surgical problems in the post-operative period (serious postoperative bleeding, wound dehiscence, etc.)-when and if these problems resolve and the patient meets other entry criteria, they will be eligible to be recruited for participation,
19. have active neuromuscular diseases that would prevent or interfere with responding to strength training (e.g., amyotrophic lateral sclerosis, multiple sclerosis, myasthenia gravis, polymyositis, muscular dystrophy or other dystrophies and myopathies), and
20. Allergic to lidocaine
21. High risk of bleeding secondary to organic conditions or medication
22. Any anatomical difficulty obtaining biopsy (such a being very overweight)
23. CPR on admission
24. Full dose anticoagulation therapy (ex. Heparin infusion, full anticoagulation dose enoxaparin, Coumadin/Warfarin/Jantoven/Marevan/Waran, and Argatroban).
25. Patient on antiplatelet therapy and medicine such as Plavix (also known as Clopidogrel, Clopilet, and Ceruvin), Aggrenox (also known as aspirin with Dipyridamol), Ticlid (also known as ticlopidine), Agrylin or Xagrid (also known as Anagrelide). Of note, aspirin is not an exclusion criteria, as long as that is the only anti-platelet medication the patient is receiving. In addition, other non steroidal anti-inflammatory agents-NSAIDS (Ibuprofen, Naproxen, Indomethicin or other anti-inflammatories) are not a contraindication to the muscle biopsy procedure and
26. any other factor in the investigators' judgment that would unnecessarily increase the risk to the patient.

Primary outcomes:
measure: Isometric muscle twitch force measured at the start of the study, approximately every seven days thereafter and final day of study.
timeFrame: Change from days 1, 7, 14, 21, and 28
measure: Change in inflammatory markers on days 1, 7, 14, 21, and 28.
timeFrame: Change from days 1, 7, 14, 21, and 28
measure: Change in immunosuppressive markers on days 1, 7, 14, 21, and 28.
timeFrame: Change from days 1, 7, 14, 21, and 28
Secondary outcomes:
measure: Measurement of key proteins of mitochondrial function using immunohistochemistry and Western blotting
timeFrame: Measurement on day 28
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: UF Health Shands Hospital at the University of Florida
state: Florida
Study officials:
affiliation: University of Florida
name: Daniel Martin, PhD, PT
role: PRINCIPAL_INVESTIGATOR
References: