Effect of Lipopolysaccharide on Skeletal Muscle Functions (LPS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by University of Nottingham
Sponsor:
Information provided by (Responsible Party):
University of Nottingham
ClinicalTrials.gov Identifier:
NCT01423968
First received: August 11, 2011
Last updated: December 3, 2012
Last verified: December 2012
  Purpose

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 Intervention
Sepsis
Biological: Lipopolysaccharide infusion

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by University of Nottingham:

Primary Outcome Measures:
  • Skeletal Muscle Protein Turnover (muscle tracer incorporation) [ Time Frame: 4 hr following LPS infusion ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Whole body glucose disposal [ Time Frame: 4 h Glucose insulin clamp ] [ Designated as safety issue: No ]
  • Expression of genes that regulate muscle protein balance and insulin signalling [ Time Frame: 4 h following LPS infusion ] [ Designated as safety issue: No ]

Estimated Enrollment: 8
Study Start Date: July 2011
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: Lipopolysaccharide infusion
    Lipopolysaccharide 4 nanogram/kg body weight
    Other Name: Endotoxin
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.

  Eligibility

Ages Eligible for Study:   18 Years to 30 Years
Genders 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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01423968

Contacts
Contact: Kanagaraj Marimuthu, MS, MRCS 01158230199 kanagaraj.marimuthu@nottingham.ac.uk
Contact: Paul Greenhaff, PhD 01158230133 paul.greenhaff@nottingham.ac.uk

Locations
United Kingdom
Queens Medical Centre Recruiting
Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
Contact: Kanagaraj Marimuthu, MS, MRCS       kanagaraj.marimuthu@nottingham.ac.uk   
Sub-Investigator: Kanagaraj Marimuthu, MS, MRCS         
Principal Investigator: Paul Greenhaff, PhD         
Sub-Investigator: Dileep N Lobo, MS, DM, FRCS         
Sub-Investigator: Ravi Mahajan, MD, DM, FRCA         
Sponsors and Collaborators
University of Nottingham
Investigators
Principal Investigator: Paul L Greenhaff, PhD Professor of Muscle Metabolism, University of Nottingham
  More Information

No publications provided

Responsible Party: University of Nottingham
ClinicalTrials.gov Identifier: NCT01423968     History of Changes
Other Study ID Numbers: B/12/2010
Study First Received: August 11, 2011
Last Updated: December 3, 2012
Health Authority: United Kingdom: Research Ethics Committee

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

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

ClinicalTrials.gov processed this record on August 21, 2014