Safety and Feasibility of an Endotoxemia Model

Sponsor

Penn State University (Other)

Overall Status

Completed

CT.gov ID

NCT01329965

Collaborator

USDA Beltsville Human Nutrition Research Center (U.S. Fed)

Enrollment

Location

Arms

Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Study Design

Study Type:

Interventional

Actual Enrollment :

6 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Official Title:

Safety and Feasibility of an Endotoxemia Model: Pilot Study

Study Start Date :

Apr 1, 2011

Actual Primary Completion Date :

Aug 1, 2011

Actual Study Completion Date :

Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
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.

Arm

Intervention/Treatment

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)

Outcome Measures

Primary Outcome Measures

Change in Inflammatory Markers [Baseline (before LPS administration), 1, 2, 3, 4, 6, 12, 24 hrs post LPS administration; 2, 3 and 5 days post LPS administration]

Secondary Outcome Measures

Change in Lipid Mediators [1, 2, 3 and 5 days post LPS administration]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 35 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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