Inflammation and the Metabolic Syndrome in Humans (LPS)

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT00954824
First received: August 5, 2009
Last updated: August 6, 2009
Last verified: August 2009
  Purpose

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.


Condition Intervention
Metabolic Syndrome X
Biological: Endotoxin (LPS)

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Health Services Research
Official Title: Inflammation and the Metabolic Syndrome in Humans

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • The primary outcome measure is plasma levels of TNF alpha. The goals are to compare responses between lean non metabolic syndrome subjects and overweight metabolic syndrome participants. [ Time Frame: 24 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The goals are to compare responses between (a) Lean non metabolic syndrome subjects and overweight non metabolic syndrome participants (b) Overweight non metabolic syndrome subjects and overweight metabolic syndrome participants [ Time Frame: 24 hours ] [ Designated as safety issue: No ]

Enrollment: 51
Study Start Date: August 2003
Study Completion Date: November 2007
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: LPS

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.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00954824

Locations
United States, Pennsylvania
Clinical and Translational Research Center, Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
Investigators
Principal Investigator: Muredach P. Reilly, MB, MSCE University of Pennsylvania
  More Information

Publications:

Responsible Party: Muredach P. Reilly, M.B., M.S.C.E., University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00954824     History of Changes
Other Study ID Numbers: 706771, 1RO1HL73278-01
Study First Received: August 5, 2009
Last Updated: August 6, 2009
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Inflammation
Metabolic Syndrome X
Pathologic Processes
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on July 22, 2014