Effect of Lipopolysaccharide on Skeletal Muscle Functions

NCT ID: NCT01423968

Last Updated: 2018-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-31
• Study Completion Date: 2012-12-31

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.

Conditions

Sepsis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Lipopolysaccharide infusion

Lipopolysaccharide infusion; dosage 4ng/kg body weight

Group Type: EXPERIMENTAL

Lipopolysaccharide infusion

Intervention Type: BIOLOGICAL

Lipopolysaccharide 4 nanogram/kg body weight

saline

0.9% saline infusion

Group Type: PLACEBO_COMPARATOR

saline

Intervention Type: OTHER

Interventions

Lipopolysaccharide infusion

Lipopolysaccharide 4 nanogram/kg body weight

Intervention Type: BIOLOGICAL

saline

Intervention Type: OTHER

Other Intervention Names

Endotoxin; 0.9% saline infusion

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Nottingham

OTHER

Sponsor Role: lead

Responsible Party

Elizabeth Simpson

Senior Research Fellow

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Paul L Greenhaff, PhD

Role: PRINCIPAL_INVESTIGATOR

Professor of Muscle Metabolism, University of Nottingham

Locations

Queens Medical Centre

Nottingham, Nottinghamshire, United Kingdom

Countries

United Kingdom

Other Identifiers

B/12/2010

Identifier Type: -

Identifier Source: org_study_id