Skeletal Muscle Wasting and Insulin Resistance Following Surgical Stress

Background: Skeletal muscle wasting or decrease in muscle mass occurs as a result of alteration in the body's mechanisms to make or break muscle protein. In animal models, the pathway termed as 'ubiquitin-proteasome pathway' (UPP) is primarily responsible for the regulation of skeletal muscle protein loss in wasting conditions and during infection(sepsis). Skeletal muscle wasting is noticed in patients having major surgery due to the inflammatory reaction triggered by special group of proteins called cytokines (inflammatory proteins), resulting in reduced muscle strength, impaired capacity to fight infections, change in bowel function, increased clinical complications and prolonged recovery. Major surgery also leads to decreased sensitivity to hormone known as insulin, resulting in 'diabeteslike'state.

We hypothesize that susceptibility of patients undergoing major abdominal surgery, to skeletal muscle wasting and insulin resistance, is determined by stress response to surgery over time, leading to changes in the pathways that make or break muscle protein, namely the Akt/Foxo signalling and UPP. Therefore, the aim of this study is to establish the underlying mechanisms of skeletal muscle wasting and insulin resistance in patients undergoing major abdominal surgery.

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Key information

Conditions

Insulin Resistance Glucose Metabolism Disorders Hyperinsulinism Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

University Hospitals Nottingham Queen's Medical Centre

Nottingham, NG7 2UH, United Kingdom

About this study

Experimental plan Fifteen adult patients undergoing major open elective abdominal surgery will be included in this nonrandomized study.

Objectives:

To study the expression proteins and metabolites involved in UPP mediated protein degradation, in blood and muscle biopsy samples.
To correlate the effects of surgery on the release of bacteria in blood from the bowel.

The analysis of the samples will include the following techniques, namely, RTPCR, ELISA, western blotting and metabolomics.

Establishing the association between these signaling mechanisms and expression of the individual proteins secondary to inflammation following surgery and infection would enable application of suitable therapeutic strategies that could reduce the inflammatory response to benefit all patients undergoing surgery.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

All adult patients undergoing major open elective gastrointestinal surgery lasting 3 hours or more will be eligible for the study.

Exclusion criteria

Patients who are:

undergoing emergency surgery
suffering from chronic illness, (e.g. diabetes) or other debilitating diseases
on long term anti-inflammatory drugs, (e.g. NSAIDS, Steroids, immunosuppressant)
on long term antibiotics
on statins
on full therapeutic dose of anticoagulants, or aspirin > 325 mg/day, clopidogrel > 75 mg/day
suffering from bleeding diathesis
unable to give consent
pregnant or breastfeeding

Treatment and study plan

Major abdominal Surgery

Procedure

All adult patients having major abdominal surgery

Primary outcomes

postoperative insulin resistance

Time frame: First week following surgery

Sponsors and collaborators

Lead sponsor

University of Nottingham

Other

Registry information

Official study title

Does Surgical Stress Impair Skeletal Muscle Protein and Carbohydrate Metabolism?

Acronym: SIRSS

Important dates

Study start: 2010
Primary completion: 2013
Study completion: 2013
First posted: Jun 2, 2010
Registry last updated: Jun 9, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed