Effect of Enteral Genistein Supplementation in Sepsis

• ClinicalTrials.gov Identifier: NCT02796794
• Recruitment Status: Unknown
• First Posted: June 13, 2016
• Last Update Posted: June 13, 2016
• Sponsor: TC Erciyes University
• Information provided by (Responsible Party): Kursat Gundogan, TC Erciyes University

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Sepsis	Dietary Supplement: Genistein; Other: enteral nutrition only	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of Enteral Genistein Supplementation on Inflammatory Cytokines, Morbidity and Mortality in Patients With Sepsis
• Study Start Date: June 2015
• Estimated Primary Completion Date: September 2016
• Estimated Study Completion Date: September 2016

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Genistein; Intervention group will receive supplemental genistein (60 mg/day) to enteral nutrition	Dietary Supplement: Genistein; 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
control; Control group are the patients receiving enteral nutrition	Other: enteral nutrition only; These are the patients receiving enteral nutrition

Outcome Measures

Primary Outcome Measures :

1. Change in Tumor necrosis factor alpha serum levels [ Time Frame: Baseline, at 24th hour and at 72nd hour ]
   It will be measured at baseline, at 24th hour and at 72nd hour after inclusion into the study
2. Change in interleukin 1-beta serum levels [ Time Frame: Baseline, at 24th hour and at 72nd hour ]
   It will be measured at baseline, at 24th hour and at 72nd hour after inclusion into the study
3. Change in interleukin 6 serum levels [ Time Frame: Baseline, at 24th hour and at 72nd hour ]
   It will be measured at baseline, at 24th hour and at 72nd hour after inclusion into the study
4. Change in high-mobility group box 1 serum levels [ Time Frame: Baseline, at 24th hour and at 72nd hour ]
   It will be measured at baseline, at 24th hour and at 72nd hour after inclusion into the study

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Kursat Gundogan, MD; +90 352 207 6666 ext 21919; kgundogan@erciyes.edu.tr

Contact: Murat Sungur, MD; +90 352 207 6666 ext 21912; msungur@erciyes.edu.tr

Locations

Turkey

Erciyes University Medical School; Recruiting

Kayseri, Turkey, 38039

Contact: Kudret Dogru, MD +90 352 207 6666 ext 20000 kdogru@erciyes.edu.tr

Contact: Emine Alp, MD +90 352 207 6666 ext 20000 ealp@erciyes.edu.tr

Sponsors and Collaborators

TC Erciyes University

More Information

Publications:

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.

Lazarevic B, Hammarström C, Yang J, Ramberg H, Diep LM, Karlsen SJ, Kucuk O, Saatcioglu F, Taskèn 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.

Hong H, Landauer MR, Foriska MA, Ledney GD. Antibacterial activity of the soy isoflavone genistein. J Basic Microbiol. 2006;46(4):329-35.

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. Review. Erratum in: N Engl J Med. 2013 Nov 21;369(21):2069.

• Responsible Party: Kursat Gundogan, MD, TC Erciyes University
• ClinicalTrials.gov Identifier: NCT02796794
• Other Study ID Numbers: 2014/341
• First Posted: June 13, 2016
• Last Update Posted: June 13, 2016
• Last Verified: June 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Kursat Gundogan, TC Erciyes University:

Enteral nutrition; Genistein; Cytokine

Additional relevant MeSH terms:

Sepsis; Toxemia; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Genistein; Anticarcinogenic Agents; Protective Agents; Physiological Effects of Drugs; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Phytoestrogens; Estrogens, Non-Steroidal; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists