Effect of Enteral Genistein Supplementation in Sepsis

Study Overview
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Brief Summary
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To evaluate effects of genistein supplementation to enteral nutrition on inflammatory cytokines and morbidity in patients with sepsis

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

Official Title
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Effect of Enteral Genistein Supplementation on Inflammatory Cytokines, Morbidity and Mortality in Patients With Sepsis

Conditions
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Sepsis

Intervention / Treatment
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* Dietary Supplement: Genistein
* Other: enteral nutrition only


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Genistein<br>Intervention group will receive supplemental genistein (60 mg/day) to enteral nutrition | Dietary Supplement: Genistein<br>* Total 30 patients will be included into the study They will be divided into two groups each containing 15 patients. Intervention group will receive supplemental genistein (60 mg/day) to enteral nutrition<br>|
| Other: control<br>Control group are the patients receiving enteral nutrition | Other: enteral nutrition only<br>* These are the patients receiving enteral nutrition<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Tumor necrosis factor alpha serum levels | It will be measured at baseline, at 24th hour and at 72nd hour after inclusion into the study | Baseline, at 24th hour and at 72nd hour | 
| Change in interleukin 1-beta serum levels | It will be measured at baseline, at 24th hour and at 72nd hour after inclusion into the study | Baseline, at 24th hour and at 72nd hour | 
| Change in interleukin 6 serum levels | It will be measured at baseline, at 24th hour and at 72nd hour after inclusion into the study | Baseline, at 24th hour and at 72nd hour | 
| Change in high-mobility group box 1 serum levels | It will be measured at baseline, at 24th hour and at 72nd hour after inclusion into the study | Baseline, at 24th hour and at 72nd hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of study participants with development of new pneumonia, urinary tract infection and blood stream infections | Patients will be followed until they are discharged from the hospital or death. | From date of randomization until 12 weeks | 
| Length of intensive care unit and hospital stay (days) | Patients will be followed until they are discharged from the hospital or death. | From date of randomization until 12 weeks | 
| Duration of mechanical ventilation | Patients will be followed until they are discharged from the hospital or death. | From date of randomization until 12 weeks | 
| Intensive care unit mortality rate, hospital mortality rate | Patients will be followed until they are discharged from the hospital or death. | From date of randomization until 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Enteral nutrition, Genistein, Cytokine