Cardiovascular Disease (CVD)NCT02107053
The Effect of Pomegranate Juice (PJ) on Oxidative Stress Biomarkers During Treatment With IV Iron During One Dialysis Session
A study testing PJ and IV iron in people with Cardiovascular Disease (CVD), run by Western Galilee Hospital-Nahariya at 1 site in Israel.
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. Read more about this study
- Who is it for?
- Ages 20 to 95 years
- Conditions the study is for
- Cardiovascular Disease (CVD)
- What is being tested?
- PJ and IV iron
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteIsrael
- Study dates
- Apr 2014to Jan 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 95 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- patients on hemodialysis
Who cannot join
- patients with infections or cancer
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Pomegranate Juice on Oxidative Stress Biomarkers During Treatment With IV Iron During One Dialysis Session
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.
Read the detailed 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.
- Conditions
- Cardiovascular Disease (CVD)
- Being tested
- PJ, IV iron
- Keywords
- Oxidative stress,, hemodialysis,, pomegranate juice,, dietary supplement, patients
- Medical subject headings
- Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PJDietary supplement
Also called pomegranate juice
IV ironDrug
IV iron is routinely administered to dialysis patients worldwide to correct anemia
| Study group | Role | What they receive |
|---|---|---|
| IV iron + PJ | Experimental | Each patient will serve as a self control Receives: Dietary Supplement: PJ; Drug: IV iron |
| No IV iron + PJ | Experimental | Each patient will serve as a self control Receives: Dietary Supplement: PJ |
| IV iron no PJ | Experimental | Each patient will serve as a self control Receives: Drug: IV iron |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Immediately before and after dialysis, for 4 various protocols
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2014 (estimated)
- Study startApr 2014
- Primary completionOct 2015
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular Disease (CVD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Western Galilee Hospital-Nahariya
- Sponsor type
- Other government
- Collaborators
- Luoxis
- Responsible party
- Principal investigator, shifra sela, Western Galilee Hospital-Nahariya
- Investigators
- Batya Kristal, MD, Principal investigator, Western Galilee Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02107053
- Sponsor's protocol ID
- 0122-13
- Status last verified
- Feb 2016
- First submitted
- 18 Feb 2014
- Last updated
- 9 Feb 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 23746559Shema-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.
PubMed 22609423Sela 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. No abstract available.
PubMed 23318016Cohen-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. doi: 10.1152/ajpheart.00952.2007. Epub 2007 Nov 21.
PubMed 18032524Mazor 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. doi: 10.1097/HJH.0b013e3282dd79b6.
PubMed 17921819Mazor 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. doi: 10.1016/j.atherosclerosis.2007.08.014. Epub 2007 Sep 17.
PubMed 17869258Jacobi 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. doi: 10.1152/ajpheart.01040.2005. Epub 2005 Dec 30.
PubMed 16387791Jacobi 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. doi: 10.1016/j.freeradbiomed.2005.06.010. Epub 2005 Aug 8.
PubMed 16214039Sela 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. doi: 10.1681/ASN.2004110929. Epub 2005 Jun 29.
PubMed 15987755Sela 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. doi: 10.1161/01.HYP.0000144480.10207.34. Epub 2004 Sep 27.
PubMed 15452031Shurtz-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. doi: 10.2337/diacare.24.1.104.
PubMed 11194213Kristal 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. doi: 10.1016/s0895-7061(98)00099-5.
PubMed 9715783
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Pomegranate Juice on Oxidative Stress Biomarkers During Treatment With IV Iron During One Dialysis Session
- ClinicalTrials.gov ID
- NCT02107053
- Acronym / sponsor ID
- 0122-13
- Conditions
- Cardiovascular Disease (CVD)
- Keywords
- Oxidative stress,, hemodialysis,, pomegranate juice,, dietary supplement, patients
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Western Galilee Hospital-NahariyaOther government
- Collaborators
- Luoxis
- Study start
- Apr 2014
- Primary completion
- Oct 2015 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 8 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| IV iron + PJ | Experimental | Dietary Supplement: PJ, Drug: IV ironEach patient will serve as a self control |
| No IV iron + PJ | Experimental | Dietary Supplement: PJEach patient will serve as a self control |
| IV iron no PJ | Experimental | Drug: IV ironEach patient will serve as a self control |
Who may qualify
- Ages
- 20 to 95 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- patients on hemodialysis
Key exclusion criteria (1 listed)
- patients with infections or cancer
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PJAlso: pomegranate juice | Dietary supplement | IV iron + PJ, No IV iron + PJ |
| IV ironIV iron is routinely administered to dialysis patients worldwide to correct anemia | Drug | IV iron + PJ, IV iron no PJ |
Primary outcome
Oxidation reduction potential
Time frame: Immediately before and after dialysis, for 4 various protocols
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2016.
- Background: PubMed 23746559Shema-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.
- Background: PubMed 22609423Shema-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.
- Background: PubMed 23318016Sela 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. No abstract available.
- Background: PubMed 18032524Cohen-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. doi: 10.1152/ajpheart.00952.2007. Epub 2007 Nov 21.
- Background: PubMed 17921819Mazor 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. doi: 10.1097/HJH.0b013e3282dd79b6.
- Background: PubMed 17869258Mazor 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. doi: 10.1016/j.atherosclerosis.2007.08.014. Epub 2007 Sep 17.
- Background: PubMed 16387791Jacobi 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. doi: 10.1152/ajpheart.01040.2005. Epub 2005 Dec 30.
- Background: PubMed 16214039Jacobi 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. doi: 10.1016/j.freeradbiomed.2005.06.010. Epub 2005 Aug 8.
- Background: PubMed 15987755Sela 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. doi: 10.1681/ASN.2004110929. Epub 2005 Jun 29.
- Background: PubMed 15452031Sela 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. doi: 10.1161/01.HYP.0000144480.10207.34. Epub 2004 Sep 27.
- Background: PubMed 11194213Shurtz-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. doi: 10.2337/diacare.24.1.104.
- Background: PubMed 9715783Kristal 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. doi: 10.1016/s0895-7061(98)00099-5.
Related trials for Cardiovascular Disease (CVD)
Active, not recruitingPhase 3
ENDOTHELION Study Group: Effect of Bosentan in NAION Patients
Ischemic Optic Neuropathy
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Recruiting
PAW-Hydrogel for Chronic Wound Healing
Diabetic Foot Ulcer (DFU), Pressure Ulcer (PU)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Batya Kristal, MD principal investigator
Western Galilee Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PJ and IV iron in people with Cardiovascular Disease (CVD), run by Western Galilee Hospital-Nahariya at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Oxidation reduction potential (time frame: Immediately before and after dialysis, for 4 various protocols). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02107053, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2016.