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Effect of Lipopolysaccharide on Skeletal Muscle Functions (LPS)

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ClinicalTrials.gov Identifier: NCT01423968
Recruitment Status : Completed
First Posted : August 26, 2011
Last Update Posted : March 27, 2018
Sponsor:
Information provided by (Responsible Party):
Elizabeth Simpson, University of Nottingham

Brief Summary:

The investigators aim to examine how the skeletal muscles of the human volunteers respond to experimental septic conditions to aid understanding of muscle wasting and its biology..

Six healthy men aged 18-30 will be randomly assigned to two metabolic study visits. On the first visit, while resting on a bed, they will have four cannulae inserted including one in the upper thigh, for blood sampling and the infusion of insulin, glucose and normal and tracer amino acids (which allow us to measure muscle protein metabolism). Subjects will receive either injection of purified bacterial product called lipopolysaccharide (LPS) to induce flu-like symptoms or normal saline according to randomization followed by a metabolic test to stimulate muscle synthesis and glucose transport. Three small samples of muscle will be obtained under local anaesthetic from the thigh to measure molecular events in muscle. By performing these measurements, the investigators will determine the consequences of LPS on muscle production and carbohydrate metabolism.


Condition or disease Intervention/treatment Phase
Sepsis Biological: Lipopolysaccharide infusion Other: saline Not Applicable

Detailed Description:

During sepsis, the ability of the body to prevent muscle wasting is impaired resulting in loss of skeletal muscle. In addition, skeletal muscle handling of carbohydrate becomes less efficient. These changes could result in delayed recovery, prolonged rehabilitation and in severe cases mortality of patients. It is still unclear how these changes occur in the human skeletal muscles but animal experiments suggest that protein molecules that are released during sepsis are responsible for these changes. Due to the biological differences between animals and humans in metabolic rate and stability, disease susceptibility and response to infection, simple translation of knowledge from animals to patients could be highly misleading. Therefore, we aim to examine how the skeletal muscles of the human volunteers respond to experimental septic conditions.

Following medical screening, six healthy men aged 18-30 will have two metabolic study visits in a random manner. On the first visit, while resting on a bed, they will have four cannulae inserted including one in the upper thigh, for blood sampling and the infusion of insulin, glucose and normal and tracer amino acids (which allow us to measure muscle protein metabolism). Subjects will receive either injection of purified bacterial product called lipopolysaccharide (LPS) to induce flu-like symptoms or normal saline according to randomization followed by a metabolic test to stimulate muscle synthesis and glucose transport. Three small samples of muscle will be obtained under local anaesthetic from the thigh to measure molecular events in muscle. By performing these measurements, we will determine the consequences of LPS on muscle production and carbohydrate metabolism.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Impact & Time-Course of Effect of Intravenous Lipopolysaccharide Infusion on Skeletal Muscle Protein Turnover and Insulin Sensitivity in Healthy Human Volunteers
Actual Study Start Date : July 2011
Actual Primary Completion Date : December 2012
Actual Study Completion Date : December 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sepsis
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Lipopolysaccharide infusion
Lipopolysaccharide infusion; dosage 4ng/kg body weight
Biological: Lipopolysaccharide infusion
Lipopolysaccharide 4 nanogram/kg body weight
Other Name: Endotoxin
Placebo Comparator: saline
0.9% saline infusion
Other: saline
Other Name: 0.9% saline infusion



Primary Outcome Measures :
  1. Skeletal Muscle Protein Turnover (muscle tracer incorporation) [ Time Frame: 4 hr following LPS infusion ]
    incorporation of 1,2 13C-leucine into muscle tissue


Secondary Outcome Measures :
  1. Whole body glucose disposal [ Time Frame: 4 h Glucose insulin clamp ]
    Glucose uptake calculated from glucose infused to maintain euglycemia during a constant insulin infusion.

  2. Expression of genes that regulate muscle protein balance and insulin signalling [ Time Frame: 4 h following LPS infusion ]
    Changes in mRNA levels of several transcripts associated with metabolism or muscle growth in skeletal muscle



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Ages Eligible for Study:   18 Years to 30 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Male 18-30yrs

Exclusion Criteria:

Clotting disorders Metabolic disease e.g. diabetes, thyroid dysfunction Inflammatory conditions e.g. Crohn's Disease Tobacco smoker Cardiac or Renal pathology Respiratory problems including Asthma Active infectious conditions


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01423968


Locations
United Kingdom
Queens Medical Centre
Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
Sponsors and Collaborators
University of Nottingham
Investigators
Principal Investigator: Paul L Greenhaff, PhD Professor of Muscle Metabolism, University of Nottingham

Responsible Party: Elizabeth Simpson, Senior Research Fellow, University of Nottingham
ClinicalTrials.gov Identifier: NCT01423968     History of Changes
Other Study ID Numbers: B/12/2010
First Posted: August 26, 2011    Key Record Dates
Last Update Posted: March 27, 2018
Last Verified: March 2018

Keywords provided by Elizabeth Simpson, University of Nottingham:
Sepsis
Inflammation
Lipopolysaccharide
Muscle protein turnover
Insulin resistance

Additional relevant MeSH terms:
Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes