Effect of Lipopolysaccharide on Skeletal Muscle Functions

NCT01423968 | Completed

• 1 other identifier: B/12/2010
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Sepsis

Keywords

Sepsis; Inflammation; Lipopolysaccharide; Muscle protein turnover; Insulin resistance

Outcome Measures

Primary Outcomes (1)

• Skeletal Muscle Protein Turnover (muscle tracer incorporation)

  incorporation of 1,2 13C-leucine into muscle tissue

  4 hr following LPS infusion

Secondary Outcomes (2)

• Whole body glucose disposal

  4 h Glucose insulin clamp

• Expression of genes that regulate muscle protein balance and insulin signalling

  4 h following LPS infusion

Study Arms (2)

Lipopolysaccharide infusion

EXPERIMENTAL

Lipopolysaccharide infusion; dosage 4ng/kg body weight

Biological: Lipopolysaccharide infusion

saline

PLACEBO COMPARATOR

0.9% saline infusion

Other: saline

Interventions

Lipopolysaccharide infusion BIOLOGICAL

Lipopolysaccharide 4 nanogram/kg body weight

Also known as: Endotoxin

Lipopolysaccharide infusion

saline OTHER

Also known as: 0.9% saline infusion

saline

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male 18-30yrs

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Nottingham: lead

Study Sites (1)

Queens Medical Centre

Nottingham, Nottinghamshire, NG7 2UH, United Kingdom

Location

MeSH Terms

Conditions

Sepsis; Inflammation; Insulin Resistance

Interventions

Endotoxins; Sodium Chloride

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Bacterial Toxins; Toxins, Biological; Biological Factors; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Paul L Greenhaff, PhD

  Professor of Muscle Metabolism, University of Nottingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Research Fellow

Study Record Dates

• First Submitted: August 11, 2011
• First Posted: August 26, 2011
• Study Start: July 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: March 27, 2018

Record last verified: 2018-03

Locations

GB (1)