The Effect of Pomegranate Juice (PJ) on Oxidative Stress Biomarkers During Treatment With IV Iron During One Dialysis Session

Cardiovascular Disease (CVD) Clinical Trial

Official title:

The Effect of Pomegranate Juice on Oxidative Stress Biomarkers During Treatment With IV Iron During One Dialysis Session

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02107053
• Other study ID #: 0122-13
• Status: Completed
• Phase: N/A
• First received: February 18, 2014
• Last updated: February 7, 2016
• Start date: April 2014
• Est. completion date: January 2016

Study information

• Verified date: February 2016
• Source: Western Galilee Hospital-Nahariya
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

Atherosclerosis and its related cardiovascular morbidity and mortality, underlie many chronic diseases. Most atherosclerotic patients have multiple cardiovascular risk factors, which potentiate each other, causing a huge burden on health systems. In order to improve the understanding and treatment options of atherosclerosis, it is necessary to identify common basic pathways in its pathogenesis. Oxidative Stress (OS) has a major role in the pathogenesis of atherosclerosis; however, good biomarkers to determine OS are still missing.

Description:

Cardiovascular disease (CVD) is a major cause of mortality and morbidity in industrialized countries. CVD associated with atherosclerosis is the major cause of death in patients treated with hemodialysis (HD) in addition to the high morbidity and mortality due to infections. Beside the invaluable goal of improving patients' quality of life, the reduction of the high prevalence of CVD leads to a significant financial consequences by lowering the financial burden on health systems.

Recently, the investigators have reported that half a cup of pomegranate juice (PJ), exceptional for its highest levels of antioxidants, administered 3 times a week for one year at the beginning of each dialysis, had many beneficial effects. The PJ led to a significant reduction of the atherosclerotic process and the rate of hospitalization due to infections: It lowered traditional CV risk factors such as high blood pressure and lipids (triglycerides levels). It improved various systemic non-traditional cardiovascular risk factors such as neutrophil priming, oxidation adducts and pro-inflammatory factors (IL-6, TNFα). Neutrophil priming was previously reported by us as a unique non-traditional CV risk factor involved in different clinical states associated with atherosclerosis. Moreover, the investigators have shown that primed neutrophils separated from HD patients cause endothelial injury that may lead to atherosclerosis and CVD.

The PJ is, thus, effective, vital and important. Yet the PJ in its natural liquid state has an astringent taste and raises doubts and uncertainties with regards to its non-standardized commercial preparation, of undefined composition and shelf life.

The investigators propose to examine PJ or pomegranate extracts containing similar concentrations of total polyphenols as in the investigators previous study in the Turkish juice (ref #2 below), in order to make it more standardized as a dietary supplement to hemodialysis patients.

The investigators plan in this protocol to study the effects of a chosen pomegranate extracts or juice from Primor, in a clinical study in HD patients. The study will be performed in one dialysis session, with and without IV iron and with and without pomegranate juice (4-arms, same patient). Each dialysis session activates neutrophils and induces oxidative stress and inflammation. Therefore, in this clinical study the investigators will assay the beneficial effects of the PJ on oxidative stress and inflammation induced by one dialysis session exacerbated by IV iron.

Each patient will be treated the same day of the week, 4 times, altogether one month per patient.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: January 2016
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 95 Years

Eligibility

Inclusion Criteria:

• patients on hemodialysis

Exclusion Criteria:

• patients with infections or cancer

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Cardiovascular Disease (CVD)
• Cardiovascular Diseases

Intervention

Dietary Supplement:
• PJ

Drug:
• IV iron
IV iron is routinely administered to dialysis patients worldwide to correct anemia

Locations

Country	Name	City	State
Israel	Western Galilee Hospital	Nahariya

Sponsors (2)

Lead Sponsor	Collaborator
Western Galilee Hospital-Nahariya	Luoxis

Country where clinical trial is conducted

Israel, 

References & Publications (12)

Cohen-Mazor M, Sela S, Mazor R, Ilan N, Vlodavsky I, Rops AL, van der Vlag J, Cohen HI, Kristal B. Are primed polymorphonuclear leukocytes contributors to the high heparanase levels in hemodialysis patients? Am J Physiol Heart Circ Physiol. 2008 Feb;294(2):H651-8. Epub 2007 Nov 21. — View Citation

Jacobi J, Kristal B, Chezar J, Shaul SM, Sela S. Exogenous superoxide mediates pro-oxidative, proinflammatory, and procoagulatory changes in primary endothelial cell cultures. Free Radic Biol Med. 2005 Nov 1;39(9):1238-48. Epub 2005 Aug 8. — View Citation

Jacobi J, Sela S, Cohen HI, Chezar J, Kristal B. Priming of polymorphonuclear leukocytes: a culprit in the initiation of endothelial cell injury. Am J Physiol Heart Circ Physiol. 2006 May;290(5):H2051-8. Epub 2005 Dec 30. — View Citation

Kristal B, Shurtz-Swirski R, Chezar J, Manaster J, Levy R, Shapiro G, Weissman I, Shasha SM, Sela S. Participation of peripheral polymorphonuclear leukocytes in the oxidative stress and inflammation in patients with essential hypertension. Am J Hypertens. 1998 Aug;11(8 Pt 1):921-8. — View Citation

Mazor R, Kristal B, Cohen-Mazor M, Yagil C, Yagil Y, Sela S. The polymorphonuclear leukocyte contributes to the development of hypertension in the Sabra rat. J Hypertens. 2007 Nov;25(11):2249-56. — View Citation

Mazor R, Shurtz-Swirski R, Farah R, Kristal B, Shapiro G, Dorlechter F, Cohen-Mazor M, Meilin E, Tamara S, Sela S. Primed polymorphonuclear leukocytes constitute a possible link between inflammation and oxidative stress in hyperlipidemic patients. Atherosclerosis. 2008 Apr;197(2):937-43. Epub 2007 Sep 17. — View Citation

Sela S, Mazor R, Amsalam M, Yagil C, Yagil Y, Kristal B. Primed polymorphonuclear leukocytes, oxidative stress, and inflammation antecede hypertension in the Sabra rat. Hypertension. 2004 Nov;44(5):764-9. Epub 2004 Sep 27. — View Citation

Sela S, Michelis R, Kristal B. Are oxidative modifications of proteins a metabolomic signature of cardiovascular disease in CKD? Am J Kidney Dis. 2013 Feb;61(2):350-1. doi: 10.1053/j.ajkd.2012.10.022. — View Citation

Sela S, Shurtz-Swirski R, Cohen-Mazor M, Mazor R, Chezar J, Shapiro G, Hassan K, Shkolnik G, Geron R, Kristal B. Primed peripheral polymorphonuclear leukocyte: a culprit underlying chronic low-grade inflammation and systemic oxidative stress in chronic kidney disease. J Am Soc Nephrol. 2005 Aug;16(8):2431-8. Epub 2005 Jun 29. Erratum in: J Am Soc Nephrol. 2005 Sep;16(9):2814. — View Citation

Shema-Didi L, Kristal B, Ore L, Shapiro G, Geron R, Sela S. Pomegranate juice intake attenuates the increase in oxidative stress induced by intravenous iron during hemodialysis. Nutr Res. 2013 Jun;33(6):442-6. doi: 10.1016/j.nutres.2013.04.004. Epub 2013 May 9. — View Citation

Shema-Didi L, Sela S, Ore L, Shapiro G, Geron R, Moshe G, Kristal B. One year of pomegranate juice intake decreases oxidative stress, inflammation, and incidence of infections in hemodialysis patients: a randomized placebo-controlled trial. Free Radic Biol Med. 2012 Jul 15;53(2):297-304. doi: 10.1016/j.freeradbiomed.2012.05.013. Epub 2012 May 17. — View Citation

Shurtz-Swirski R, Sela S, Herskovits AT, Shasha SM, Shapiro G, Nasser L, Kristal B. Involvement of peripheral polymorphonuclear leukocytes in oxidative stress and inflammation in type 2 diabetic patients. Diabetes Care. 2001 Jan;24(1):104-10. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Oxidation reduction potential	Each patient will serve as a self control. The metric measurements will be expressed as relative to control potential. Redox potential will be measured as oxidation-reduction potential and reported in millivolts.	Immediately before and after dialysis, for 4 various protocols	No