Investigation of the Role of FHL-1 and Myostatin in Intensive Care Unit Acquired Paresis (ICUAP)
The primary hypothesis for this study is that Myostatin and FHL-1 are important in the development of ICUAP and that changes in activity levels of muscle will modify the levels of expression and activity of these proteins.
Intensive Care Unit Acquired Paresis
Other: Active muscle stimulation
|Study Design:||Intervention Model: Single Group Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Basic Science
|Official Title:||Investigation of the Role of FHL-1 and Myostatin in the Development of Intensive Care Unit Acquired Paresis (ICUAP) and the Effect of Increased Muscle Activity on These Pathways.|
- Change in muscle myostatin and FHL-1 [ Time Frame: 1 week ] [ Designated as safety issue: No ]
- Change in quadriceps cross sectional area [ Time Frame: 1 week ] [ Designated as safety issue: No ]
- Change in quadriceps strength [ Time Frame: 1 week ] [ Designated as safety issue: No ]
- Change in blood myostatin, miRNA and other markers of muscle breakdown [ Time Frame: 1 week ] [ Designated as safety issue: No ]
- Changes in muscle protein synthesis and breakdown pathways as measured in the muscle biopsy samples. [ Time Frame: 1 week ] [ Designated as safety issue: No ]
- Change in muscle breakdown and synthesis pathways as a factor of amount of muscle stimulation received. [ Time Frame: 1 week ] [ Designated as safety issue: No ]
- Change in muscle phenotype and change in cross sectional area for individual fiber types [ Time Frame: 1 week ] [ Designated as safety issue: No ]
|Study Start Date:||April 2011|
|Study Completion Date:||October 2013|
|Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
Experimental: Active stimulation
This group will receive active muscle stimulation for 1 week to the quadriceps muscle - the leg will be randomly assigned.
Other: Active muscle stimulation
Neuromuscular Electrical stimulation will be applied to one leg (randomly assigned).
ICUAP is an increasingly recognised clinical problem associated with significant morbidity and mortality. However the pathogenesis of the diseae is poorly understood and as yet no treatment exists. We believe that both myostatin and FHL-1 will be important in the development of this disease. This is based recent research and that both these proteins are likely to be regulated by sepsis and immobility (two major risk factors for ICUAP. There is evidence from invitro work that the two are likely to interact. We have designed an interventional trial to investigate the above hypothesis. Patients admitted to ICU and at risk of developing muscle wasting will be selected and receive electrical muscle stimulation of the quadriceps muscle for 1 week. Physiological measurements of peripheral and respiratory muscle strength and quadriceps size will be made pre and post intervention. And muscle biopsies, blood and urine collected from both legs pre and post intervention. The relevant molecular pathways can then be examined.
|National Heart and Lung Institute, Imperial College|
|London, United Kingdom|
|Principal Investigator:||M Polkey||Royal Brompton Hospital and Imperial College|
|Principal Investigator:||Susannah Bloch||Imperial College London|