Clinical trial NCT01423968: Effect of Lipopolysaccharide on Skeletal Muscle Functions
Official title: Impact & Time-Course of Effect of Intravenous Lipopolysaccharide Infusion on Skeletal Muscle Protein Turnover and Insulin Sensitivity in Healthy Human Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sepsis
Keywords: Sepsis
Inflammation
Lipopolysaccharide
Muscle protein turnover
Insulin resistance
Lead sponsor: University of Nottingham
Sponsor class: OTHER
First posted: 2011-08-26
Enrollment: 6
Sex: MALE
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

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 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

Primary outcomes:
measure: Skeletal Muscle Protein Turnover (muscle tracer incorporation)
timeFrame: 4 hr following LPS infusion
Secondary outcomes:
measure: Whole body glucose disposal
timeFrame: 4 h Glucose insulin clamp
measure: Expression of genes that regulate muscle protein balance and insulin signalling
timeFrame: 4 h following LPS infusion
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Queens Medical Centre
state: Nottinghamshire
Study officials:
affiliation: Professor of Muscle Metabolism, University of Nottingham
name: Paul L Greenhaff, PhD
role: PRINCIPAL_INVESTIGATOR
References: