Investigation of the Role of FHL-1 and Myostatin in Intensive Care Unit Acquired Paresis (ICUAP)

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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.

Conditions
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Intensive Care Unit Acquired Paresis, Muscle Wasting

Intervention / Treatment
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* Other: Active muscle stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: High risk patients admitted to AICU. Exclusion Criteria: Pre existing neuromuscular disease.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active stimulation<br>This group will receive active muscle stimulation for 1 week to the quadriceps muscle - the leg will be randomly assigned. | Other: Active muscle stimulation<br>* Neuromuscular Electrical stimulation will be applied to one leg (randomly assigned).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in muscle myostatin and FHL-1 |  | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in quadriceps cross sectional area |  | 1 week | 
| Change in quadriceps strength |  | 1 week | 
| Change in blood myostatin, miRNA and other markers of muscle breakdown |  | 1 week | 
| Changes in muscle protein synthesis and breakdown pathways as measured in the muscle biopsy samples. |  | 1 week | 
| Change in muscle breakdown and synthesis pathways as a factor of amount of muscle stimulation received. |  | 1 week | 
| Change in muscle phenotype and change in cross sectional area for individual fiber types |  | 1 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ICUAP, Critical illness, Muscle wasting, ICU