NCT02699905

Brief Summary

This study seeks to elucidate the quantitative expression of G - protein receptor 43/free fatty acid (GPR43/FFA2) receptors in patients with the diagnosis of sepsis and specifically, its expression as it relates to the severity of sepsis. The investigators hypothesize that patients with more severe sepsis, as defined by a higher SOFA (Sequential Organ Failure Assessment Score), will have decreased expression of the GPR43/FFA2 as compared to patients with lower SOFA scores, consistent with a less exuberant immune response to infection. Patients admitted to Penn State Hershey Medical Center with a diagnosis of sepsis of any cause will undergo blood testing of leukocytes to determine the expressed quantity of GP43 during standardized time points of their illness and recovery. No interventions will be made in the standard clinical management of the patient. Additionally, healthy volunteers will be recruited to exam baseline GPR43 receptor expression between sepsis and control groups.

Trial Health

15
At Risk

Trial Health Score

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

Trial has exceeded expected completion date
Timeline
Completed

Started Aug 2016

Status
withdrawn

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

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 1, 2016

Completed
6 days until next milestone

First Posted

Study publicly available on registry

March 7, 2016

Completed
5 months until next milestone

Study Start

First participant enrolled

August 1, 2016

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2017

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2017

Completed
Last Updated

January 13, 2017

Status Verified

January 1, 2017

Enrollment Period

1 year

First QC Date

March 1, 2016

Last Update Submit

January 11, 2017

Conditions

SepsisSeptic ShockMultiple Organ DysfunctionIntra-abdominal Sepsis

Keywords

SepsisSeptic ShockMultiple Organ DysfunctionFFA2GPR43

Outcome Measures

Primary Outcomes (1)

  • Quantitative FFA2/GPR43 receptor expression as a function of SOFA score

    Quantitative expression of FFA2/GPR43 will be measured at specific time intervals and compared to SOFA score.

    Time of diagnosis, 24, 72, 168 hour intervals

Study Arms (2)

Sepsis

Patients with the diagnosis of sepsis or septic shock

Other: phlebotomy

Control

Healthy control with no evidence of active infection, or recent infection in the past 4 weeks.

Other: phlebotomy

Interventions

phlebotomyOTHER

phlebotomy

ControlSepsis

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Adult patients with the diagnosis of sepsis or septic shock admitted to the intensive care unit at Penn State Hershey Medical Center, Hershey PA 17033.

You may qualify if:

  • Diagnosis of sepsis or septic shock
  • Age greater than eighteen years old.
  • Ability to give informed consent (as determined by the attending physician) or presence of designated healthcare proxy that can give informed consent.

You may not qualify if:

  • Patients or designated healthcare proxy with the inability to give informed consent.
  • Patients under the age of eighteen

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (13)

  • Covington DK, Briscoe CA, Brown AJ, Jayawickreme CK. The G-protein-coupled receptor 40 family (GPR40-GPR43) and its role in nutrient sensing. Biochem Soc Trans. 2006 Nov;34(Pt 5):770-3. doi: 10.1042/BST0340770.

    PMID: 17052194BACKGROUND

  • Brown AJ, Goldsworthy SM, Barnes AA, Eilert MM, Tcheang L, Daniels D, Muir AI, Wigglesworth MJ, Kinghorn I, Fraser NJ, Pike NB, Strum JC, Steplewski KM, Murdock PR, Holder JC, Marshall FH, Szekeres PG, Wilson S, Ignar DM, Foord SM, Wise A, Dowell SJ. The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem. 2003 Mar 28;278(13):11312-9. doi: 10.1074/jbc.M211609200. Epub 2002 Dec 19.

    PMID: 12496283BACKGROUND

  • Cox MA, Jackson J, Stanton M, Rojas-Triana A, Bober L, Laverty M, Yang X, Zhu F, Liu J, Wang S, Monsma F, Vassileva G, Maguire M, Gustafson E, Bayne M, Chou CC, Lundell D, Jenh CH. Short-chain fatty acids act as antiinflammatory mediators by regulating prostaglandin E(2) and cytokines. World J Gastroenterol. 2009 Nov 28;15(44):5549-57. doi: 10.3748/wjg.15.5549.

    PMID: 19938193BACKGROUND

  • Vinolo MA, Ferguson GJ, Kulkarni S, Damoulakis G, Anderson K, Bohlooly-Y M, Stephens L, Hawkins PT, Curi R. SCFAs induce mouse neutrophil chemotaxis through the GPR43 receptor. PLoS One. 2011;6(6):e21205. doi: 10.1371/journal.pone.0021205. Epub 2011 Jun 15.

    PMID: 21698257BACKGROUND

  • Sina C, Gavrilova O, Forster M, Till A, Derer S, Hildebrand F, Raabe B, Chalaris A, Scheller J, Rehmann A, Franke A, Ott S, Hasler R, Nikolaus S, Folsch UR, Rose-John S, Jiang HP, Li J, Schreiber S, Rosenstiel P. G protein-coupled receptor 43 is essential for neutrophil recruitment during intestinal inflammation. J Immunol. 2009 Dec 1;183(11):7514-22. doi: 10.4049/jimmunol.0900063. Epub 2009 Nov 16.

    PMID: 19917676BACKGROUND

  • Masui R, Sasaki M, Funaki Y, Ogasawara N, Mizuno M, Iida A, Izawa S, Kondo Y, Ito Y, Tamura Y, Yanamoto K, Noda H, Tanabe A, Okaniwa N, Yamaguchi Y, Iwamoto T, Kasugai K. G protein-coupled receptor 43 moderates gut inflammation through cytokine regulation from mononuclear cells. Inflamm Bowel Dis. 2013 Dec;19(13):2848-56. doi: 10.1097/01.MIB.0000435444.14860.ea.

    PMID: 24141712BACKGROUND

  • Kim MH, Kang SG, Park JH, Yanagisawa M, Kim CH. Short-chain fatty acids activate GPR41 and GPR43 on intestinal epithelial cells to promote inflammatory responses in mice. Gastroenterology. 2013 Aug;145(2):396-406.e1-10. doi: 10.1053/j.gastro.2013.04.056. Epub 2013 May 7.

    PMID: 23665276BACKGROUND

  • Senga T, Iwamoto S, Yoshida T, Yokota T, Adachi K, Azuma E, Hamaguchi M, Iwamoto T. LSSIG is a novel murine leukocyte-specific GPCR that is induced by the activation of STAT3. Blood. 2003 Feb 1;101(3):1185-7. doi: 10.1182/blood-2002-06-1881. Epub 2002 Sep 19.

    PMID: 12393494BACKGROUND

  • Le Poul E, Loison C, Struyf S, Springael JY, Lannoy V, Decobecq ME, Brezillon S, Dupriez V, Vassart G, Van Damme J, Parmentier M, Detheux M. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J Biol Chem. 2003 Jul 11;278(28):25481-9. doi: 10.1074/jbc.M301403200. Epub 2003 Apr 23.

    PMID: 12711604BACKGROUND

  • Bindels LB, Dewulf EM, Delzenne NM. GPR43/FFA2: physiopathological relevance and therapeutic prospects. Trends Pharmacol Sci. 2013 Apr;34(4):226-32. doi: 10.1016/j.tips.2013.02.002. Epub 2013 Mar 13.

    PMID: 23489932BACKGROUND

  • Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996 Jul;22(7):707-10. doi: 10.1007/BF01709751. No abstract available.

    PMID: 8844239BACKGROUND

  • Yao YM, Redl H, Bahrami S, Schlag G. The inflammatory basis of trauma/shock-associated multiple organ failure. Inflamm Res. 1998 May;47(5):201-10. doi: 10.1007/s000110050318.

    PMID: 9657252RESULT

  • Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001 Jul;29(7):1303-10. doi: 10.1097/00003246-200107000-00002.

    PMID: 11445675RESULT

Biospecimen

Retention: SAMPLES WITH DNA

10 mL of whole blood drawn at four time intervals during the study. Blood is centrifuged and the Buffy coat separated and flash frozen in liquid nitrogen. Quantitative PCR analysis is then performed to assess the expression of FFA2/GPR43 at different time points in the patient's illness.

MeSH Terms

Conditions

SepsisShock, Septic

Interventions

Phlebotomy

Condition Hierarchy (Ancestors)

InfectionsSystemic Inflammatory Response SyndromeInflammationPathologic ProcessesPathological Conditions, Signs and SymptomsShock

Intervention Hierarchy (Ancestors)

Blood Specimen CollectionSpecimen HandlingClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisPuncturesTherapeuticsSurgical Procedures, OperativeInvestigative Techniques
0

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor, Department of Anesthesiology & Perioperative Medicine

Study Record Dates

First Submitted

March 1, 2016

First Posted

March 7, 2016

Study Start

August 1, 2016

Primary Completion

August 1, 2017

Study Completion

November 1, 2017

Last Updated

January 13, 2017

Record last verified: 2017-01

Data Sharing

IPD Sharing
Will share