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Effect of Lipopolysaccharide on Skeletal Muscle Functions (LPS)

U

University of Nottingham

Status

Completed

Conditions

Sepsis

Treatments

Biological: Lipopolysaccharide infusion
Other: saline

Study type

Interventional

Funder types

Other

Identifiers

NCT01423968
B/12/2010

Details and patient eligibility

About

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.

Full 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.

Enrollment

6 patients

Sex

Male

Ages

18 to 30 years old

Volunteers

Accepts Healthy Volunteers

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

Trial design

Primary purpose

Basic Science

Allocation

Randomized

Interventional model

Crossover Assignment

Masking

Quadruple Blind

6 participants in 2 patient groups, including a placebo group

Lipopolysaccharide infusion
Experimental group
Description:
Lipopolysaccharide infusion; dosage 4ng/kg body weight
Treatment:
Biological: Lipopolysaccharide infusion
saline
Placebo Comparator group
Description:
0.9% saline infusion
Treatment:
Other: saline

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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