Clinical trial NCT02589535: Circulating Stem Cells, SDF-1, HIF-1 and Sepsis's Indices in Emergency Abdominal Surgical Patients
Official title: Circulating Stem Cells, SDF-1, HIF-1 and Sepsis: Relationship Between Indices of Sepsis and Emergency Abdominal Surgical Patients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Sepsis
Lead sponsor: University of Foggia
Sponsor class: OTHER
Collaborators: name: Fondo di Sviluppo e Coesione 2007-2013 APQ RicercaRegionePuglia FutureInResearch
First posted: 2015-10-28
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: postoperative patients undergoing major abdominal surgery

Brief summary: Septic shock is a systemic inflammatory response syndrome with acute circulatory failure secondary to a documented infection. It is the most feared complication in ICU patients, with a 50% mortality rate.

The study of stem cells and their experimental use in sepsis treatment is particularly relevant in the international scientific research, where Italy plays an important role. In the vast and complex field of stem cell research, the primary aim of the current proposal is to evaluate the time course level of circulating endothelial progenitor stem cells CD34 + / CD133 + (EPCs), and some factors EPCs-related, such as hypoxia- inducible factor (HIF- 1) and stromal derived factor-1 (SDF-1) in septic patients undergoing major abdominal surgery.

Secondary objective 2: to investigate the relationship between CD133/CD34, HIF-1, SDF-1a and outcome of septic/septic shock patients treated with standard conventional therapy alone (CT) or with extracorporeal hemoperfusion therapy (HCT).

Detailed description: Primary objective: to determine the time course level of the circulating EPC (CD133/CD34), SDF-1a, and HIF-1 in septic patients undergoing major abdominal surgery.

Secondary objective 1: to investigate the relationship between these factors: CD133/CD34, HIF-1 and SDF-1a.

Secondary objective 2: to investigate the relationship between CD133/CD34, HIF-1, SDF-1° and outcomeof septic/septic shock patients treated with standard conventional therapy alone (CT) or with extracorporeal hemoperfusion therapy (HCT).

In this trial, we hypothesize that CD133/CD34, HIF1 and SDF1a will increase in septic surgical patients as consequence of impaired tissue perfusion and cellular hypoxia. Our hypothesis is based on the fact that the stimulation of factors hypoxia-related, as SDF-1a and HIF-1 could be the primary step for bone marrow stem cells stimulation. Furthermore, we assume that survivors septic patients will show higher levels of EPC, HIF-1 and SDF-1a.

Each day, the anesthesiologist of the operating room and the on-call anesthesiologist will alerts the principal investigator to a potential eligible patient. Participants included in the trial will be divided into two groups:

* C group: postoperative non septic patients in emergency surgical ward (ES) (control group)
* S group: postoperative septic shock patients in intensive care unit (ICU) Healthy volunteers (H group) will be recruited from among staff members of the University Hospital of Foggia

The research study can provide useful parameters for early diagnostic and therapeutic interventions in sepsis which is the leading cause of death from infection, with an incidence of approximately 10% in ICU postoperative patients according to recent epidemiologic studies.

Eligibility criteria: Inclusion criteria:

Caucasian, Over 18 years of age

Exclusion criteria:

when it is impossible to collect blood samples (organizational reasons or because of emergencies regarding the health of the patients),Pregnant patients,Organ transplantation, Palliative care,Metastatic cancer patients

Primary outcomes:
measure: time course level of circulating endothelial progenitor stem cells CD133+/CD34+, HIF1 and SDF in septic patients undergoing emergency major abdominal surgery.
timeFrame: 1-10 days after intervention
Secondary outcomes:
measure: correlation among time course level of circulating stem cells, hypoxia-inducible factor-1 (HIF-1) and stromal derived factor - 1 (SDF-1)
timeFrame: 1-10 days after intervention
measure: relationship between CD133/CD34, HIF-1, SDF-1a and outcome.
timeFrame: 1-10 days after intervention
Other outcomes:
Locations:
city: Foggia
country: Italy
facility: University of Foggia
Study officials:
affiliation: Klinikum Ludwigshafen
name: Antonella Cotoia, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Friedrich EB, Walenta K, Scharlau J, Nickenig G, Werner N. CD34-/CD133+/VEGFR-2+ endothelial progenitor cell subpopulation with potent vasoregenerative capacities. Circ Res. 2006 Feb 17;98(3):e20-5. doi: 10.1161/01.RES.0000205765.28940.93. Epub 2006 Jan 26.
citation: Cribbs SK, Martin GS, Rojas M. Monitoring of endothelial dysfunction in critically ill patients: the role of endothelial progenitor cells. Curr Opin Crit Care. 2008 Jun;14(3):354-60. doi: 10.1097/MCC.0b013e3282fc216d.
citation: Kalil AC, Florescu MC. Blood purification: can we purify our patients from sepsis? Crit Care Med. 2013 Sep;41(9):2244-5. doi: 10.1097/CCM.0b013e318291cad5. No abstract available.
citation: Cotoia A, Cela O, Palumbo G, Altamura S, Marchese F, Mangialetto N, La Bella D, Lizzi V, Capitanio N, Cinnella G. High mobilization of CD133+/CD34+ cells expressing HIF-1alpha and SDF-1alpha in septic abdominal surgical patients. BMC Anesthesiol. 2020 Jun 27;20(1):158. doi: 10.1186/s12871-020-01068-w.
citation: Cotoia A, Mirabella L, Altamura S, Villani R, Marchese F, Ferrara G, Mariano K, Livio T, Cinnella G. Circulating stem cells, HIF-1, and SDF-1 in septic abdominal surgical patients: randomized controlled study protocol. Trials. 2018 Mar 12;19(1):179. doi: 10.1186/s13063-018-2556-0.