Clinical trial NCT02796794: Effect of Enteral Genistein Supplementation in Sepsis
Official title: Effect of Enteral Genistein Supplementation on Inflammatory Cytokines, Morbidity and Mortality in Patients With Sepsis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Sepsis
Keywords: Enteral nutrition
Genistein
Cytokine
Lead sponsor: TC Erciyes University
Sponsor class: OTHER
First posted: 2016-06-13
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate effects of genistein supplementation to enteral nutrition on inflammatory cytokines and morbidity in patients with sepsis

Detailed description: Sepsis is a state develops as a response to severe infection with high mortality rate. Incidence of sepsis among patients admitted to hospitals is 2%. Annual incidence of sepsis is 50-95 for 100.000 population and incidence is increasing approximately 9% each year. Severe sepsis and septic shock is the most frequent reason for mortality in intensive care units (ICU). There is exaggerated and irregular host response in sepsis. Cytokines such as interleukin-1, interleukin-6, interleukin-8, tumor necrosis factor-α, Interferon-γ and high mobility group box-1 are released as response to invading microorganisms and they play a major role in sepsis pathogenesis.

Soybean proteins are used for prevention and treatment of cardiovascular diseases, osteoporosis and different cancer types.

Soy isoflavones such as genistein, daidzein and glycitein are the main components for cancer prevention. Genistein is the dominant isoflavones.

The main mechanism for anti-inflammatory effect of genistein is related to transcription nuclear factor (NF-kB) and inhibition of chemokine-8. The risk for prostate cancer was proven to decrease in epidemiological studies.

NF-kB plays a central role for inflammatory cytokine release, prevents apoptosis and induces tumor cell growth. The effect of topoisomerase II inhibitory chemotherapeutic agents is increased with NF-kB inhibition.

Hypothesis

1. Addition of genistein to enteral nutrition in patients with sepsis can play an important role to decrease inflammatory cytokines.
2. Morbidity can be decreased with lower levels of inflammatory cytokines in patients with sepsis.

Eligibility criteria: Criteria: inclusion criteria:

* Patients with sepsis above 18 years of age.
* Expected duration of ICU survival more than 48 hours.
* Patients receiving enteral nutrition (EN)
* Sepsis diagnosis within first 12 hours

Exclusion Criteria:

* Presence of thyroid dysfunction
* Presence of hyperlipidemia
* Patients with nill by mouth and not receiving enteral nutrition

Primary outcomes:
measure: Change in Tumor necrosis factor alpha serum levels
timeFrame: Baseline, at 24th hour and at 72nd hour
measure: Change in interleukin 1-beta serum levels
timeFrame: Baseline, at 24th hour and at 72nd hour
measure: Change in interleukin 6 serum levels
timeFrame: Baseline, at 24th hour and at 72nd hour
measure: Change in high-mobility group box 1 serum levels
timeFrame: Baseline, at 24th hour and at 72nd hour
Secondary outcomes:
measure: Number of study participants with development of new pneumonia, urinary tract infection and blood stream infections
timeFrame: From date of randomization until 12 weeks
measure: Length of intensive care unit and hospital stay (days)
timeFrame: From date of randomization until 12 weeks
measure: Duration of mechanical ventilation
timeFrame: From date of randomization until 12 weeks
measure: Intensive care unit mortality rate, hospital mortality rate
timeFrame: From date of randomization until 12 weeks
Other outcomes:
Locations:
city: Kayseri
country: Turkey
facility: Erciyes University Medical School
Study officials:
References:
citation: Souza LR, Silva E, Calloway E, Kucuk O, Rossi M, McLemore ML. Genistein protects hematopoietic stem cells against G-CSF-induced DNA damage. Cancer Prev Res (Phila). 2014 May;7(5):534-44. doi: 10.1158/1940-6207.CAPR-13-0295. Epub 2014 Mar 10.
citation: Lazarevic B, Hammarstrom C, Yang J, Ramberg H, Diep LM, Karlsen SJ, Kucuk O, Saatcioglu F, Tasken KA, Svindland A. The effects of short-term genistein intervention on prostate biomarker expression in patients with localised prostate cancer before radical prostatectomy. Br J Nutr. 2012 Dec 28;108(12):2138-47. doi: 10.1017/S0007114512000384. Epub 2012 Mar 8.
citation: Hong H, Landauer MR, Foriska MA, Ledney GD. Antibacterial activity of the soy isoflavone genistein. J Basic Microbiol. 2006;46(4):329-35. doi: 10.1002/jobm.200510073.
citation: Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013 Aug 29;369(9):840-51. doi: 10.1056/NEJMra1208623. No abstract available.