Effect of Lipopolysaccharide on Skeletal Muscle Functions
Condition: Sepsis
MeSH terms: Sepsis
Study type: Interventional

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.
    

Intervention name(s): Lipopolysaccharide infusion; saline
Intervention type(s): Biological; Other
Intervention description(s): Lipopolysaccharide 4 nanogram/kg body weight
Other intervention name(s): Endotoxin; 0.9% saline infusion
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Sepsis; Inflammation; Lipopolysaccharide; Muscle protein turnover; Insulin resistance