Safety and Feasibility of an Endotoxemia Model - Full Text View

Purpose

The purpose of this study is to establish the safety and feasibility of low dose LPS administration to a small subset of humans in preparation for a larger USDA funded study examining what is the lowest effective dose of EPA + DHA (300, 600, 900 and 1,800 mg/day delivered as fish oil supplements) that significantly attenuates the inflammatory response the investigators wish to examine the effects of an endotoxemia model for inducing inflammation. Based on previous research, low dose LPS administration affects metabolism in humans with only minimal clinical effects (such as "flu" like illness). Therefore, each of the six subjects included in this small pilot study will receive a low dose of LPS and placebo in order to learn more about the metabolic changes that occur during administration and inflammation. The investigators hypothesis that LPS administration will elicit only minimal clinical effects (such as "flu" like illness) when compared to placebo (saline--water with the same amount of salt as in your blood).

Condition	Intervention	Phase
Cardiovascular Disease Inflammation	Drug: LPS (reference endotoxin, E. coli O113:H10:K:neg, manufactured under GMP)	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Subject)
Official Title:	Safety and Feasibility of an Endotoxemia Model: Pilot Study

Further study details as provided by Penn State University:

Primary Outcome Measures:

Change in Inflammatory Markers [ Time Frame: Baseline (before LPS administration), 1, 2, 3, 4, 6, 12, 24 hrs post LPS administration; 2, 3 and 5 days post LPS administration ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Change in Lipid Mediators [ Time Frame: 1, 2, 3 and 5 days post LPS administration ] [ Designated as safety issue: No ]

Enrollment:	6
Study Start Date:	April 2011
Study Completion Date:	September 2011
Primary Completion Date:	August 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: LPS LPS will be injected at a dose of 0.6 ng/kg body weight through a catheter by a trained GCRC staff member involved with this study.	Drug: LPS (reference endotoxin, E. coli O113:H10:K:neg, manufactured under GMP) LPS or placebo (saline—salt water) will be injected (at approximately 7:30 am) in this catheter by a trained GCRC staff member involved with this study. Participants will not be told if they have received the drug or placebo. The LPS is a sterile solution of protein-free endotoxin which will be injected at a dose of 0.6 ng/kg body weight. Blood samples will be collected from a venous catheter for the first 12 hours and by venipuncture thereafter. Subjects will be continuously monitored by trained nursing staff for blood pressure (q 15 minutes) and body temperature (q 30 minutes), and the study will have physician oversight.
Placebo Comparator: Saline A saline solution will be injected through a catheter by a trained GCRC staff member involved with this study.	Drug: LPS (reference endotoxin, E. coli O113:H10:K:neg, manufactured under GMP) LPS or placebo (saline—salt water) will be injected (at approximately 7:30 am) in this catheter by a trained GCRC staff member involved with this study. Participants will not be told if they have received the drug or placebo. The LPS is a sterile solution of protein-free endotoxin which will be injected at a dose of 0.6 ng/kg body weight. Blood samples will be collected from a venous catheter for the first 12 hours and by venipuncture thereafter. Subjects will be continuously monitored by trained nursing staff for blood pressure (q 15 minutes) and body temperature (q 30 minutes), and the study will have physician oversight.

Arms

Assigned Interventions

Experimental: LPS

LPS will be injected at a dose of 0.6 ng/kg body weight through a catheter by a trained GCRC staff member involved with this study.

Drug: LPS (reference endotoxin, E. coli O113:H10:K:neg, manufactured under GMP)

LPS or placebo (saline—salt water) will be injected (at approximately 7:30 am) in this catheter by a trained GCRC staff member involved with this study. Participants will not be told if they have received the drug or placebo. The LPS is a sterile solution of protein-free endotoxin which will be injected at a dose of 0.6 ng/kg body weight. Blood samples will be collected from a venous catheter for the first 12 hours and by venipuncture thereafter. Subjects will be continuously monitored by trained nursing staff for blood pressure (q 15 minutes) and body temperature (q 30 minutes), and the study will have physician oversight.

Placebo Comparator: Saline

A saline solution will be injected through a catheter by a trained GCRC staff member involved with this study.

Drug: LPS (reference endotoxin, E. coli O113:H10:K:neg, manufactured under GMP)

LPS or placebo (saline—salt water) will be injected (at approximately 7:30 am) in this catheter by a trained GCRC staff member involved with this study. Participants will not be told if they have received the drug or placebo. The LPS is a sterile solution of protein-free endotoxin which will be injected at a dose of 0.6 ng/kg body weight. Blood samples will be collected from a venous catheter for the first 12 hours and by venipuncture thereafter. Subjects will be continuously monitored by trained nursing staff for blood pressure (q 15 minutes) and body temperature (q 30 minutes), and the study will have physician oversight.

Eligibility

Ages Eligible for Study:	20 Years to 35 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Healthy men and non-pregnant/lactating women between the ages of 20 and 35 years old
BMI > 19.9 and < 30.0
Able to give written informed consent and willing to comply with all study- related procedures

Exclusion Criteria:

Previous history of heart disease or diabetes
Renal Insufficiency
Chronic anti-inflammatory use
Systolic blood pressure < 90
Individuals currently using tobacco products or have done so in the previous 30 days
Individuals taking Omega-3 fatty acid supplements or their usual intake of fish is greater than 3-4 servings per month

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01329965

Locations

United States, Pennsylvania
Penn State University
University Park, Pennsylvania, United States, 16802

Sponsors and Collaborators

Penn State University

USDA Beltsville Human Nutrition Research Center

Investigators

Principal Investigator:

Penny M Kris-Etherton, PhD, RD

Penn State University

More Information

No publications provided

Responsible Party:	Penny Kris-Etherton, Distinguished Professor of Nutrition, Penn State University
ClinicalTrials.gov Identifier:	NCT01329965 History of Changes
Other Study ID Numbers:	PKE LPSpilot
Study First Received:	April 1, 2011
Last Updated:	March 14, 2013
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board

Keywords provided by Penn State University:

Cardiovascular disease
Inflammation
LPS
Endotoxin

Additional relevant MeSH terms:

Cardiovascular Diseases
Inflammation
Endotoxemia
Pathologic Processes
Bacteremia

Sepsis
Infection
Toxemia
Systemic Inflammatory Response Syndrome

ClinicalTrials.gov processed this record on June 17, 2013