Inflammation and the Metabolic Syndrome in Humans (LPS)

March 28, 2017 updated by: University of Pennsylvania
People who are overweight are at increased risk of heart disease. Being overweight and having heart disease are linked in that both involve inflammation. Inflammation refers to the body's first line of defense against infection and injury. Metabolic changes in cholesterol, triglycerides (fat in the blood) and sugar in the blood caused by inflammation are similar to that in some people who are overweight. The investigators wish to examine the effects of inflammation on these metabolic changes that may lead to heart disease.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study is a single site, open-label, "baseline-controlled" (pre LPS saline period) study examining the pro-atherosclerotic metabolic responses and safety responses to a single administration low-dose (3 ng/kg) endotoxin (LPS) in 20 additional non-metabolic syndrome participants: 10 healthy overweight and 10 healthy lean counterparts (20 non-metabolic syndrome participants were studies in first phase), and 40 subjects with the metabolic syndrome. We are continuing to use an approach whereby "metabolic syndrome" subjects will be recruited to have key metabolic syndrome abnormalities that are sensitive to insulin resistance compared to the non-metabolic syndrome groups, although all of these "metabolic syndrome" subjects may not fulfill traditional NCEP criteria for the syndrome.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Clinical and Translational Research Center, Hospital of the University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Men and non-pregnant/lactating women between the ages of 18 and 40
  2. Subjects must be able to give written informed consent and willing to comply with all study-related procedures.
  3. BMI >18 and < 24 and BIA < 15% fat for men, < 25% fat for women, and do not have diagnosis of NCEP metabolic syndrome as defined below, OR
  4. BMI > 26 but < 30 and BIA > 15% fat for men, > 25% fat for women, do not have diagnosis of NCEP metabolic syndrome, OR

  5. BMI >18 and < 30 and have metabolic syndrome abnormalities as defined below. The modified NCEP Metabolic Syndrome criteria are as follows

    • abdominal obesity, waist circumference: men >= 37 in (94 cm), women >= 31 in (80 cm)
    • fasting triglycerides > 150 mg/dL
    • HDL cholesterol < 40 mg/dL for men; HDL cholesterol < 50 mg/dL for women
    • Blood pressure > 130/ >85 mmHg in untreated patients
    • Fasting glucose > 100 mg/dL, but less than 126 mg/dL

  6. For inclusion in "metabolic syndrome" group, the following additional criteria must be fulfilled:

    • Three or more of the NCEP criteria defined above. OR
    • Two or more of the NCEP criteria AND TG/HDL ratio > 3.0.

Exclusion Criteria:

  1. Known atherosclerotic cardiovascular disease, including coronary disease, cerebrovascular disease, or peripheral vascular disease.
  2. History of diabetes mellitus.
  3. A plasma glucose greater than 200 mg/dL at the 2 hour blood draw of the oral glucose tolerance test.
  4. History of a non-skin malignancy within the previous 5 years.
  5. Renal insufficiency as defined by creatinine >= 1.5 mg/dl at visit 1 (grade 1 of NIH's Common Toxicity Criteria (CTC), version 2.0, 4/30/99).
  6. History of liver disease or ALT, AST, ALK Phosphatase or Gamma GT above normal limits as defined by HUP William Pepper Clinical Laboratory at visit 1.
  7. Elevated (> 1.5x ULN; grade 1, CTC, 4/30/99) Total Bilirubin or LDH at visit 1.
  8. Men who consume > 14 alcoholic drinks per week or > 4 alcoholic drinks per occasion (AMA/NIAAA criteria for "at risk" usage levels).
  9. Women who consume > 7 alcoholic drinks per week or > 3 alcoholic drinks per occasion (AMA/NIAAA criteria for "at risk" usage levels).
  10. Total white blood cell count below normal limits as defined at HUP William Pepper Clinical Laboratory prior to the baseline visit.
  11. Hemoglobin below normal limits (gender specific) as defined at HUP William Pepper Clinical Laboratory prior to the baseline visit.
  12. Any medical condition or abnormal laboratory value that is judged clinically significant by an investigator.
  13. Any major active rheumatologic, pulmonary, or dermatologic disease or inflammatory condition or minor active infection.
  14. History of HIV positive.
  15. First degree family history of premature cardiovascular disease event (father or brother if diagnosed at before 55 years of age; mother or sister if diagnosed before 65 years of age).
  16. Patients who have undergone any organ transplant.
  17. Individuals who currently use tobacco products or have done so in the previous 30 days.
  18. Treatment with aspirin, NSAIDs, COX-2 inhibitors, steroids or other immunomodulatory therapy 2 weeks prior to the screening visit
  19. Treatment with statins, fibrates or niacin 4 weeks prior to the screening visit.
  20. Current daily use of Vitamin C > 1000 mg, Beta carotene > 1000 IU, vitamin A > 5000 IU, vitamin E > 400 IU, and selenium > 200 mcg.
  21. Positive urine pregnancy at the screening visit.
  22. Participation in another clinical trial within the previous 6 weeks prior to the screening visit.
  23. Poorly controlled blood pressure (BP > 160/100) or on any anti-hypertensive medications.
  24. For subjects in non-metabolic syndrome groups; a diagnosis of metabolic syndrome using NCEP ATPIII criteria.
  25. For subjects in "metabolic syndrome" group; an abnormal Bruce protocol cardiac exercise stress test.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Endotoxin (LPS)
Single administration low-dose (3 ng/kg) endotoxin (LPS).
Biological: Endotoxin (LPS)
Single administration low-dose (3 ng/kg) endotoxin (LPS).
Other Names:
  • LPS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The Primary Outcome Measure is Plasma Levels of TNF Alpha.
Time Frame: 24 hours
24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pennsylvania

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

  • Principal Investigator: Muredach P. Reilly, MB, MSCE, University of Pennsylvania

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2003

Primary Completion (Actual)

November 1, 2007

Study Completion (Actual)

November 1, 2007

Study Registration Dates

First Submitted

August 5, 2009

First Submitted That Met QC Criteria

August 6, 2009

First Posted (Estimate)

August 7, 2009

Study Record Updates

Last Update Posted (Actual)

March 30, 2017

Last Update Submitted That Met QC Criteria

March 28, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 706771
  • 1R01HL073278-01 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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