Skeletal Muscle Wasting and Insulin Resistance Following Surgical Stress

NCT ID: NCT01134809

Last Updated: 2015-06-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

15 participants

Study Classification

OBSERVATIONAL

Study Start Date

2010-05-31

Study Completion Date

2013-05-31

Brief Summary

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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.

Detailed Description

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

Objectives:

1. To study the expression proteins and metabolites involved in UPP mediated protein degradation, in blood and muscle biopsy samples.
2. 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.

Conditions

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Insulin Resistance

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Major abdominal surgery

Patients having major abdominal surgery

Major abdominal surgery

Intervention Type PROCEDURE

All adult patients having major abdominal surgery

Interventions

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Major abdominal surgery

All adult patients having major abdominal surgery

Intervention Type PROCEDURE

Eligibility Criteria

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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:

1. undergoing emergency surgery
2. suffering from chronic illness, (e.g. diabetes) or other debilitating diseases
3. on long term anti-inflammatory drugs, (e.g. NSAIDS, Steroids, immunosuppressant)
4. on long term antibiotics
5. on statins
6. on full therapeutic dose of anticoagulants, or aspirin \> 325 mg/day, clopidogrel \> 75 mg/day
7. suffering from bleeding diathesis
8. unable to give consent
9. pregnant or breastfeeding
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Nottingham

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Dileep N Lobo, Professor

Role: STUDY_CHAIR

University of Notitngham

Locations

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University Hospitals Nottingham Queen's Medical Centre

Nottingham, Nottingham, United Kingdom

Site Status

Countries

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United Kingdom

References

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Atkins R, Constantin-Teodosiu D, Varadhan KK, Constantin D, Lobo DN, Greenhaff PL. Major elective abdominal surgery acutely impairs lower limb muscle pyruvate dehydrogenase complex activity and mitochondrial function. Clin Nutr. 2021 Mar;40(3):1046-1051. doi: 10.1016/j.clnu.2020.07.006. Epub 2020 Jul 14.

Reference Type DERIVED
PMID: 32711950 (View on PubMed)

Varadhan KK, Constantin-Teodosiu D, Constantin D, Greenhaff PL, Lobo DN. Inflammation-mediated muscle metabolic dysregulation local and remote to the site of major abdominal surgery. Clin Nutr. 2018 Dec;37(6 Pt A):2178-2185. doi: 10.1016/j.clnu.2017.10.020. Epub 2017 Nov 2.

Reference Type DERIVED
PMID: 29129636 (View on PubMed)

Other Identifiers

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09106

Identifier Type: -

Identifier Source: org_study_id

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