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

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ClinicalTrials.gov Identifier: NCT01681823
Recruitment Status : Recruiting
First Posted : September 10, 2012
Last Update Posted : July 25, 2018
Sponsor:
Information provided by (Responsible Party):
EcoNugenics

Tracking Information
First Submitted Date  ICMJE September 6, 2012
First Posted Date  ICMJE September 10, 2012
Last Update Posted Date July 25, 2018
Study Start Date  ICMJE June 2013
Estimated Primary Completion Date August 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 31, 2014)
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).
Original Primary Outcome Measures  ICMJE
 (submitted: September 6, 2012)
Prostate Specific Antigen (PSA) kinetics in men with biochemical relapsed prostate cancer and serial increases in PSA levels. [ Time Frame: 12 months ]
PSA doubling time increase will be used to show effectiveness of the Modified Citrus pectin (MCP).
Change History Complete list of historical versions of study NCT01681823 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 31, 2014)
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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 6, 2012)
An assessment of adverse side effects due to Modified Citrus Pectin (MCP). [ Time Frame: 12 months ]
Patient tolerability of MCP will be assessed by comparing the results of weekly self-assessment diaries with baseline assessments.
Current Other Pre-specified Outcome Measures
 (submitted: March 31, 2014)
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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of Modified Citrus Pectin on PSA Kinetics in Biochemical Relapsed PC With Serial Increases in PSA
Official Title  ICMJE 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
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Intervention Model Description:
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).
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostatic Neoplasms
Intervention  ICMJE 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).
Study Arms  ICMJE 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.
Intervention: Dietary Supplement: PectaSol-C Modified Citrus Pectin (MCP)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 28, 2012)
60
Original Estimated Enrollment  ICMJE
 (submitted: September 6, 2012)
50
Estimated Study Completion Date  ICMJE September 2019
Estimated Primary Completion Date August 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 21 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Daniel Keizman, M.D. +972 (0)9 747 2714 danielkeizman@gmail.com
Contact: Moshe Frenkel, M.D. +972 (0)52 331 1255 office@moshefrenkelmd.com
Listed Location Countries  ICMJE Israel
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01681823
Other Study ID Numbers  ICMJE MMC12192-12CTIL
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party EcoNugenics
Study Sponsor  ICMJE EcoNugenics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account EcoNugenics
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP