Effect of Modified Citrus Pectin on PSA Kinetics in Biochemical Relapsed PC With Serial Increases in PSA

January 27, 2020 updated by: EcoNugenics

Phase III, Single-Center, Open Label, Trial Evaluating the Safety and Efficacy of PectaSol-C Modified Citrus Pectin on PSA Kinetics in Prostate Cancer in the Setting of Serial Increases in PSA

To determine if the oral administration of PectaSol-C Modified Citrus Pectin (MCP) is effective at improving Prostate Specific Antigen (PSA) kinetics in men with biochemical relapsed prostate cancer and serial increases in PSA levels. Also, documentation of any side effects or benefits within parameter of the study is included.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study on the effect of PectaSol-C Modified Citrus Pectin (MCP) with subjects selected on the basis of documented PC post local therapy, and biochemical relapse, with linear progression of at least 3 PSA tests in at least 3 months. After initial screening, treatment {4.8 grams (6 capsules) three times a day away from meals} will continue for 6 months provided patients are showing benefit and tolerating the therapy well. Patient tolerability of MCP will be assessed by comparing the results of monthly self-assessment diaries with baseline assessments.

Prostate cancer is the most common cancer among men, except for non melanoma skin cancer. It is the second leading cause of cancer related death in men. About 33% of prostate cancer patients treated with primary therapy (surgery or radiation) will recur in the form of non metastatic biochemically relapsed prostate cancer (BRPC-M0). In these patients, PSA is rising while scans are negative for metastasis. Recent surveys demonstrated that approximately 40% of prostate cancer patients use various complementary and alternative medicine modalities as a component of therapy. Currently, there is no standard treatment for biochemical failure with proven benefits. Patients are being encouraged to enroll in clinical trials to help establish standards of care. Studies have shown that in 80% of patients with BRPC-M0, PSA will rise by at least 25% every 6 months.

Native pectin is a complex carbohydrate soluble fiber. Dietary fibers, such as pectin, have been shown to have positive effects on a wide spectrum of pathological conditions. Their positive influence on human health is explained by their antioxidative, hypocholesterolemic, and anticancer effects. MCP is composed of short, slightly-branched, carbohydrate chains derived from the soluble albedo fraction of citrus fruit peels, which have been altered by decreasing the molecular weight and degree of esterification using pH, temperature, and a controlled enzymatic process. This specific modification is critical as it allows for the absorption of MCP into the circulatory system and ensures its targeted bioactivity throughout the body. MCP is relatively rich in galactose and thus antagonizes the binding protein galectin-3 which results in suppression of cancer cell aggregation, adhesion, and metastasis. MCP acts as a ligand for galectin-3, which plays a major role in tumor formation and progression. It has been shown using a combination of fluorescence microscopy, flow cytometry, and atomic force microscopy, that pectin galactan specifically binds to the recombinant form of human galectin-3.

MCP showed anti-metastatic effects on cancer cells in multiple in vitro and in vivo studies. MCP inhibits carbohydrate mediated tumor growth, angiogenesis and metastasis via effects on galectin-3 function as demonstrated in an animal study on MCP's inhibition of breast and colon cancer progression. Results demonstrated a 70.2% reduction in breast tumor growth, a 66% reduction in breast angiogenesis, and 0% breast to lung metastasis compared to 100% in the control group; 0% colon to liver metastasis compared to 60% in the control group; and 25% colon to lymph metastasis compared to 100% in the control group. In an earlier study oral intake of MCP had been shown to act as a potent inhibitor of spontaneous prostate carcinoma metastasis in an animal model, demonstrating a significant 56% reduction in lung metastases. Human cancer cell lines (LNCaP androgen dependent & PC3 androgen independent) and mouse prostate cancer cell lines (CASP2-1 androgen dependent and CASP1-1 androgen independent) treated with 1% MCP showed the following cytotoxicity due to induced apoptosis: 52.28% in LNCaP; 48.16% in PC3; 23.03% in CASP2-1; and 49.01% in CASP1-1.13 The effects of MCP on cell-cell and cell-matrix interactions mediated by carbohydrate-recognition were investigated by looking at MCP-inhibited B16-F1 melanoma cells adhesion and aggregation. MCP was shown to inhibit anchorage-independent growth of B16-F1 cells. These results indicate that carbohydrate-recognition by cell surface galectin-3 is involved in cell-extracellular matrix interaction and plays a role in anchorage-independent growth as well as the in vivo embolization of tumor cells. The modulation of the lung colonization of B16-F1 melanoma cells by MCP was first observed in 1992 when injection of MCP significantly decreased B16-F1 experimental metastasis (greater than 90%). Galectin-3 participation in the adhesion of the MDA-MB-435 cells to the endothelium was observed by the clustering of galectin-3 on endothelial cells at the sites of the contact with tumor cells, suggesting its potential functional significance for anti-adhesive therapy of cancer metastasis. The anti-metastatic effect of MCP has also been shown in reduced liver metastasis in a dose-dependent manner. The use of MCP in combination with the chemotherapy drug doxorubicin has demonstrated an increased cytotoxicity effect of inducing rapid cell death in prostate cancer cell lines DU-145 (androgen independent) through apoptosis, and in LNCaP (androgen dependant) through cell cycle arrest (G2-M arrest). These results show promise for the use of MCP with doxorubicin as an adjuvant to chemotherapy which may allow for lower dosage of the cancer drug to be used with less toxicity. A human clinical pilot trial with MCP showed an increase in prostate specific antigen doubling time, a marker of slowing the progression of prostate cancer. Clinical research on MCP also demonstrated a significant improvement in quality of life and stabilization of disease for patients with advanced solid tumors.

In addition to its therapeutic roles against cancer, MCP has been shown to remove toxic metals from the body without affecting essential minerals. In a clinical study, baseline levels of heavy metals and essential minerals were established with 24-hours urine collection prior to oral administration of MCP. 24-hours urine collection was repeated on days 1 and 6. Urinary excretion of lead, mercury, cadmium, and arsenic increased significantly, essential minerals were not changed significantly and no side effects were reported. In a hospital study in China, children with lead toxicity were given MCP. Their blood serum levels went down while corresponding lead levels in their urine increased significantly, without side effects.

MCP has immunostimulatory properties as demonstrated in human blood samples, including the activation of functional NK cells against K562 leukemic cells in culture: Unsaturated oligogalacturonic acids appear to be the immunostimulatory carbohydrates in MCP. Human blood samples collected from healthy volunteers were incubated with increasing concentrations of MCP and antibodies. After 24-hours, blood-antibody mix was lysed and run on a flow cytometer using a 3-color protocol and the % of activated T-cytotoxic cell subset, B-cell, and NK-cells, and % increase over untreated control calculated and a significant dose dependent activation was seen. The ability of the activated NK cells to induce leukemia cell death was analyzed by co-incubating MCP-treated lymphocytes with K562 T-cell leukemia cells and induced leukemia cell death was determined to be greater than 50%.

MCP has been demonstrated to be protective in experimental nephropathy with modulation of early proliferation and later galectin-3 expression, apoptosis and fibrosis by experimentally modulating galectin-3 in folic acid (FA)-induced acute kidney injury. Mice were pre-treated with normal or 1% MCP-supplemented drinking water one week before FA injection. During the initial injury phase, all FA treated mice lost weight whilst their kidneys enlarged secondary to the renal insult; these gross changes were significantly lessened in the MCP group but this was not associated with significant changes in galectin-3 expression. At a histological level, MCP clearly reduced renal cell proliferation but did not affect apoptosis. Later, during the recovery phase at two weeks, MCP-treated mice demonstrated reduced galectin-3 in association with decreased renal fibrosis, macrophages, proinflammatory cytokine expression and apoptosis. Galectin-3 inhibition by MCP was demonstrated to block Aldosterone (Aldo) induced collagen type I synthesis. Rats were treated with Aldo-salt combined MCP for 3 weeks. Hypertensive Aldo-treated rats presented vascular hypertrophy, inflammation, fibrosis, and increased aortic Gal-3 expression. MCP treatment reversed all the above effects.

MCP is affirmed as GRAS (generally regarded as safe) under the US Code of Federal Regulation 21CFR184.1588.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Kfar-Saba, Israel
        • Genitourinary Oncology Service, Institute of Oncology, Meir Medical Center, Tshernichovsky 59,

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Documented PC post local therapy with undetectable Prostate Specific Antigen (PSA), and biochemical relapse (defined as post-surgery PSA > 0.2 ng/ml; post-radiation > nadir +2 ng/ml, the PSA nadir is the lowest PSA reading achieved after treatment), with linear progression of at least 3 PSA tests in at least 3 months before the commencement of the trial.
  • All patients must have negative bone scan and CT scan for the chest-abdomen-pelvis within 2 weeks prior to study initiation.

Exclusion Criteria:

  • Psychological, familial, sociological or geographical conditions that may interfere with compliance with the study or prevent completion or compliance of protocol.
  • Other severe or poorly controlled medical condition(s).
  • Known allergies to any of the ingredients.
  • Hormonal therapy or other therapy for PC in the last 3 months.
  • Positive bone scan or CT scan of the chest-abdomen-pelvis.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PectaSol-C Modified Citrus Pectin (MCP)
Treatment with 4.8 grams PectaSol-C Modified Citrus Pectin three times a day, away from meals for six months.
Dietary supplement: PectaSol-C Modified Citrus Pectin (MCP)
Oral administration of PectaSol-C MCP (4.8 grams in six capsules three times a day away from food).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prostate Specific Antigen (PSA) kinetics in men with biochemical relapsed prostate cancer and serial increases in PSA levels.
Time Frame: 6 month endpoint.
PSA doubling time increase will be used to show effectiveness of the Modified Citrus pectin (MCP).
6 month endpoint.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
An assessment of adverse side effects due to Modified Citrus Pectin (MCP).
Time Frame: 6 month endpoint.
Patient tolerability of MCP will be assessed by comparing the results of weekly self-assessment diaries with baseline assessments.
6 month endpoint.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood Serum Analysis (Galectin-3, C-Reactive Protein, Lipid Panels)
Time Frame: 6 month endpoint.
At baseline (0 month), and end of study (6 month): Blood draw for serum levels of galectin-3, C-reactive protein, and lipid panel.
6 month endpoint.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

EcoNugenics

Investigators

  • Principal Investigator: Daniel Keizman, MD, Genitourinary Oncology Service, Institute of Oncology, Meir Medical Center
  • Study Director: Isaac Eliaz, MD, LAc, MS, Amitabha Medical Clinic and Healing Center
  • Study Chair: Moshe Frenkel, MD, Clinical Associate Professor, University of Texas

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2013

Primary Completion (Actual)

January 1, 2020

Study Completion (Actual)

January 1, 2020

Study Registration Dates

First Submitted

September 6, 2012

First Submitted That Met QC Criteria

September 6, 2012

First Posted (Estimate)

September 10, 2012

Study Record Updates

Last Update Posted (Actual)

January 29, 2020

Last Update Submitted That Met QC Criteria

January 27, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MMC12192-12CTIL

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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