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

August 5, 2009
August 6, 2009
August 2003
November 2007   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT00954824 on ClinicalTrials.gov Archive Site
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 ]
Same as current
Not Provided
Not Provided
 
Inflammation and the Metabolic Syndrome in Humans
Inflammation and the Metabolic Syndrome in Humans

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.

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.

Interventional
Not Provided
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Health Services Research
Metabolic Syndrome X
Biological: Endotoxin (LPS)
Single administration low-dose (3 ng/kg) endotoxin (LPS).
Other Name: LPS
Experimental: Endotoxin (LPS)
Single administration low-dose (3 ng/kg) endotoxin (LPS).
Intervention: Biological: Endotoxin (LPS)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
51
November 2007
November 2007   (final data collection date for primary outcome measure)

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.
Both
18 Years to 40 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00954824
706771, 1RO1HL73278-01
No
Muredach P. Reilly, M.B., M.S.C.E., University of Pennsylvania
University of Pennsylvania
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Muredach P. Reilly, MB, MSCE University of Pennsylvania
University of Pennsylvania
August 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP