Clinical trial NCT03005847: The Effect of Fermented Papaya Preparation on Patients With Chronic Kidney Disease Under Dialysis Receiving Intravenous Iron
Official title: The Effect of Fermented Papaya Preparation on Patients With Chronic Kidney Disease Under Dialysis Receiving Intravenous Iron
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Anemia
Chronic Kidney Disease Stage 5
Lead sponsor: Hadassah Medical Organization
Sponsor class: OTHER
First posted: 2016-12-29
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Fermented papaya preparation has been reported to bind and neutralize reactive oxygen species as well as iron. Patients undergoing hemodialysis are generally on iron overload status due to their inability to use iron storage adequately. The aim of this study is to evaluate the effect of FPP on the iron status of these patients.

Detailed description: Background and rationale

Patients with chronic kidney disease (CKD) on hemodialysis often suffer from anemia. The anemia is primarily caused by insufficient production by the failing kidneys of the erythroid stimulating hormone - erythropoietin (Epo). Oxidative stress may be another reason for anemia. Oxidative stress in RBCs of these patients may be caused by:

1. Passage of the blood through the plastic tubing during the dialysis procedure. We have shown oxidative stress in RBCs following passage of blood through similar tubing during leukopheresis procedure (1). Other groups reported similar effects during hemodialysis.
2. Iron overload - In order to maximize the effect of Epo, the treatment is supplemented by IV injection of iron. This iron may accumulate and cause iron overload in some hemodialyzed patients. Under normal conditions, iron is transported in the blood and enters into cells following binding the plasma protein transferrin. However, when iron content in the plasma exceeds the binding capacity of transferrin, non-transferrin-bound iron (NTBI) appears. This iron enters cells via alternative pathways, and accumulates in the cytosol, where it participates in chemical reactions (Haber-Weiss, Fenton) that generate reactive oxygen species (ROS). Excess ROS overcomes the protective cellular anti-oxidant mechanisms and becomes cytotoxic. In the erythroid system, excess ROS causes accelerated apoptosis (programmed cell death) of precursor cells in the bone marrow and a short survival of mature RBCs in the circulation, resulting in chronic anemia. Excess iron and ROS may also damage other cells and lead to malfunctioning of vital organs, such as the heart and liver (2,3).

   FPP has been reported to bind and neutralize (scavenge) ROS (4) as well as free iron (chelate) (5). Both activities ameliorate the oxidative stress.

   Treatment with FPP of various diseases associated with oxidative stress, administered orally (3 gr. X 3 times a day), have been shown to significantly ameliorate the symptoms underlying these diseases (6-18). FPP has a long track-record of safe human consumption (19-20). It has been used for many years as a food-supplement by thousands of people around the world without any reported side effect.

   Research goals

   To study the effect of fermented papaya preparation (FPP) on patients with chronic kidney disease (CKD) under dialysis, receiving intravenous iron.

   General Protocol:

   This will be a single-arm, open-label, single-center study in 20 patients upon dialysis receiving IV iron supplementation. All participants will be treated with FPP for 3 months.

   Bi-weekly, blood samples will be drawn and the patients will be monitored for assessment of safety and efficacy.

   Detailed Protocol Twenty patients, treated on Hadassah Medical center, Jerusalem, will be screened and recruited according to clinical criteria.

   inclusion criteria: Age 18-70. Any primary kidney disease resulting in ESRD. Hemodynamically stable status. PTH up to 2-9 times upper normal limits. Patients receiving ESA may be included.
3. Exclusion criteria:

Any evidence of acute bleeding. Hg level of less than 8 g/dL Patients with known allergy to Papaya

3. Patients will be treated orally with FPP (3 gr. X 3 times a day) for 3 months.

4. Blood samples will be obtained from all patients prior and during (every 2 weeks) treatment.

5. Samples will be analyzed for:

Blood chemistry for Potassium, Albumin and Phosphorous (every 2 weeks).

Anemia: Complete blood count, including RBC number and indexes, as well as hemoglobin content.

Oxidative stress: (once monthly) Reactive oxygen species Reduced glutathione Membrane lipid peroxidation External phosphatidylserine

Iron overload: (once monthly) Serum ferritin Serum transferin. Labile plasma iron Serum hepcidin Intracellular labile iron pool

Safety measures:

Adverse events: Frequency, severity, seriousness, time to onset, duration, and relatedness to study product.

Eligibility criteria: Inclusion Criteria:

* Age 18-70. Any primary kidney disease resulting in ESRD. Hemodynamically stable status. PTH up to 2-9 times upper normal limits. Patients receiving ESA may be included.

Exclusion Criteria:

* Any evidence of acute bleeding. Hg level of less than 8 g/dL Patients with known allergy to Papaya

Primary outcomes:
measure: Iron status
timeFrame: 3 months of treatment
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Hadassah Medical Organization
name: itamar sagiv, MD
role: PRINCIPAL_INVESTIGATOR
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