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

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.

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.

Study Overview

• Status: Completed
• Conditions: Muscle Wasting; Intensive Care Unit Acquired Paresis
• Intervention / Treatment: Other: Active muscle stimulation

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.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • National Heart and Lung Institute, Imperial College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• High risk patients admitted to AICU.

Exclusion Criteria:

• Pre existing neuromuscular disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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).

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: Medical Research Council; Royal Brompton & Harefield NHS Foundation Trust
• Investigators: Principal Investigator: M Polkey, Royal Brompton Hospital and Imperial College; Principal Investigator: Susannah Bloch, Imperial College London

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: March 22, 2011
• First Submitted That Met QC Criteria: March 22, 2011
• First Posted (Estimate): March 23, 2011

Study Record Updates

• Last Update Posted (Estimate): October 17, 2013
• Last Update Submitted That Met QC Criteria: October 16, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: ICU; Critical illness; Muscle wasting; ICUAP
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Nervous System Diseases; Neurologic Manifestations; Nutrition Disorders; Body Weight; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Body Weight Changes; Atrophy; Emaciation; Weight Loss; Muscle Weakness; Muscular Atrophy; Wasting Syndrome; Cachexia; Paresis
• Other Study ID Numbers: CRO1439