Clinical trial NCT01321320: Investigation of the Role of FHL-1 and Myostatin in Intensive Care Unit Acquired Paresis (ICUAP)
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Intensive Care Unit Acquired Paresis
Muscle Wasting
Keywords: ICUAP
Critical illness
Muscle wasting
ICU
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Medical Research Council
name: Royal Brompton & Harefield NHS Foundation Trust
First posted: 2011-03-23
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

* High risk patients admitted to AICU.

Exclusion Criteria:

* Pre existing neuromuscular disease.

Primary outcomes:
measure: Change in muscle myostatin and FHL-1
timeFrame: 1 week
Secondary outcomes:
measure: Change in quadriceps cross sectional area
timeFrame: 1 week
measure: Change in quadriceps strength
timeFrame: 1 week
measure: Change in blood myostatin, miRNA and other markers of muscle breakdown
timeFrame: 1 week
measure: Changes in muscle protein synthesis and breakdown pathways as measured in the muscle biopsy samples.
timeFrame: 1 week
measure: Change in muscle breakdown and synthesis pathways as a factor of amount of muscle stimulation received.
timeFrame: 1 week
measure: Change in muscle phenotype and change in cross sectional area for individual fiber types
timeFrame: 1 week
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: National Heart and Lung Institute, Imperial College
Study officials:
affiliation: Royal Brompton Hospital and Imperial College
name: M Polkey
role: PRINCIPAL_INVESTIGATOR
affiliation: Imperial College London
name: Susannah Bloch
role: PRINCIPAL_INVESTIGATOR
References: