NCT00954824

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Aug 2003

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2003

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2007

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2007

Completed
1.8 years until next milestone

First Submitted

Initial submission to the registry

August 5, 2009

Completed
2 days until next milestone

First Posted

Study publicly available on registry

August 7, 2009

Completed
6.5 years until next milestone

Results Posted

Study results publicly available

January 28, 2016

Completed
Last Updated

March 30, 2017

Status Verified

March 1, 2017

Enrollment Period

4.3 years

First QC Date

August 5, 2009

Results QC Date

August 17, 2015

Last Update Submit

March 28, 2017

Conditions

Metabolic Syndrome X

Outcome Measures

Primary Outcomes (1)

  • The Primary Outcome Measure is Plasma Levels of TNF Alpha.

    24 hours

Study Arms (1)

Endotoxin (LPS)

EXPERIMENTAL

Single administration low-dose (3 ng/kg) endotoxin (LPS).

Biological: Endotoxin (LPS)

Interventions

Endotoxin (LPS)BIOLOGICAL

Single administration low-dose (3 ng/kg) endotoxin (LPS).

Also known as: LPS
Endotoxin (LPS)

Eligibility Criteria

Age18 Years - 40 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Men and non-pregnant/lactating women between the ages of 18 and 40
  • Subjects must be able to give written informed consent and willing to comply with all study-related procedures.
  • 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
  • BMI \> 26 but \< 30 and BIA \> 15% fat for men, \> 25% fat for women, do not have diagnosis of NCEP metabolic syndrome, OR
  • 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
  • Three or more of the NCEP criteria defined above. OR
  • Two or more of the NCEP criteria AND TG/HDL ratio \> 3.0.

You may not qualify if:

  • Known atherosclerotic cardiovascular disease, including coronary disease, cerebrovascular disease, or peripheral vascular disease.
  • History of diabetes mellitus.
  • A plasma glucose greater than 200 mg/dL at the 2 hour blood draw of the oral glucose tolerance test.
  • History of a non-skin malignancy within the previous 5 years.
  • 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).
  • 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.
  • Elevated (\> 1.5x ULN; grade 1, CTC, 4/30/99) Total Bilirubin or LDH at visit 1.
  • Men who consume \> 14 alcoholic drinks per week or \> 4 alcoholic drinks per occasion (AMA/NIAAA criteria for "at risk" usage levels).
  • Women who consume \> 7 alcoholic drinks per week or \> 3 alcoholic drinks per occasion (AMA/NIAAA criteria for "at risk" usage levels).
  • Total white blood cell count below normal limits as defined at HUP William Pepper Clinical Laboratory prior to the baseline visit.
  • Hemoglobin below normal limits (gender specific) as defined at HUP William Pepper Clinical Laboratory prior to the baseline visit.
  • Any medical condition or abnormal laboratory value that is judged clinically significant by an investigator.
  • Any major active rheumatologic, pulmonary, or dermatologic disease or inflammatory condition or minor active infection.
  • History of HIV positive.
  • 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).
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Clinical and Translational Research Center, Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (9)

  • Anderson PD, Mehta NN, Wolfe ML, Hinkle CC, Pruscino L, Comiskey LL, Tabita-Martinez J, Sellers KF, Rickels MR, Ahima RS, Reilly MP. Innate immunity modulates adipokines in humans. J Clin Endocrinol Metab. 2007 Jun;92(6):2272-9. doi: 10.1210/jc.2006-2545. Epub 2007 Mar 20.

    PMID: 17374708BACKGROUND

  • Heffron SP, Parastatidis I, Cuchel M, Wolfe ML, Tadesse MG, Mohler ER 3rd, Ischiropoulos H, Rader DJ, Reilly MP. Inflammation induces fibrinogen nitration in experimental human endotoxemia. Free Radic Biol Med. 2009 Oct 15;47(8):1140-6. doi: 10.1016/j.freeradbiomed.2009.07.025. Epub 2009 Jul 22.

    PMID: 19631267BACKGROUND

  • Shah R, Lu Y, Hinkle CC, McGillicuddy FC, Kim R, Hannenhalli S, Cappola TP, Heffron S, Wang X, Mehta NN, Putt M, Reilly MP. Gene profiling of human adipose tissue during evoked inflammation in vivo. Diabetes. 2009 Oct;58(10):2211-9. doi: 10.2337/db09-0256. Epub 2009 Jul 6.

    PMID: 19581417BACKGROUND

  • McGillicuddy FC, de la Llera Moya M, Hinkle CC, Joshi MR, Chiquoine EH, Billheimer JT, Rothblat GH, Reilly MP. Inflammation impairs reverse cholesterol transport in vivo. Circulation. 2009 Mar 3;119(8):1135-45. doi: 10.1161/CIRCULATIONAHA.108.810721. Epub 2009 Feb 16.

    PMID: 19221221BACKGROUND

  • Badellino KO, Wolfe ML, Reilly MP, Rader DJ. Endothelial lipase is increased in vivo by inflammation in humans. Circulation. 2008 Feb 5;117(5):678-85. doi: 10.1161/CIRCULATIONAHA.107.707349. Epub 2008 Jan 22.

    PMID: 18212282BACKGROUND

  • Song WL, Wang M, Ricciotti E, Fries S, Yu Y, Grosser T, Reilly M, Lawson JA, FitzGerald GA. Tetranor PGDM, an abundant urinary metabolite reflects biosynthesis of prostaglandin D2 in mice and humans. J Biol Chem. 2008 Jan 11;283(2):1179-88. doi: 10.1074/jbc.M706839200. Epub 2007 Nov 8.

    PMID: 17993463BACKGROUND

  • Lehrke M, Millington SC, Lefterova M, Cumaranatunge RG, Szapary P, Wilensky R, Rader DJ, Lazar MA, Reilly MP. CXCL16 is a marker of inflammation, atherosclerosis, and acute coronary syndromes in humans. J Am Coll Cardiol. 2007 Jan 30;49(4):442-9. doi: 10.1016/j.jacc.2006.09.034. Epub 2007 Jan 12.

    PMID: 17258089BACKGROUND

  • Reilly MP, Lehrke M, Wolfe ML, Rohatgi A, Lazar MA, Rader DJ. Resistin is an inflammatory marker of atherosclerosis in humans. Circulation. 2005 Feb 22;111(7):932-9. doi: 10.1161/01.CIR.0000155620.10387.43. Epub 2005 Feb 14.

    PMID: 15710760BACKGROUND

  • Lehrke M, Reilly MP, Millington SC, Iqbal N, Rader DJ, Lazar MA. An inflammatory cascade leading to hyperresistinemia in humans. PLoS Med. 2004 Nov;1(2):e45. doi: 10.1371/journal.pmed.0010045. Epub 2004 Nov 30.

    PMID: 15578112BACKGROUND

MeSH Terms

Conditions

Metabolic Syndrome

Interventions

EndotoxinsLipopolysaccharides

Condition Hierarchy (Ancestors)

Insulin ResistanceHyperinsulinismGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Bacterial ToxinsToxins, BiologicalBiological FactorsGlycoconjugatesCarbohydratesPolysaccharides, BacterialPolysaccharidesLipidsAntigens, BacterialAntigens

Results Point of Contact

Title
Muredach Reilly
Organization
UPenn
muredach@mail.med.upenn.edu
215-573-1214

Study Officials

  • Muredach P. Reilly, MB, MSCE

    University of Pennsylvania

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
HEALTH SERVICES RESEARCH
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 5, 2009

First Posted

August 7, 2009

Study Start

August 1, 2003

Primary Completion

November 1, 2007

Study Completion

November 1, 2007

Last Updated

March 30, 2017

Results First Posted

January 28, 2016

Record last verified: 2017-03

Locations

US(1)