<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01681823</url>
  </required_header>
  <id_info>
    <org_study_id>MMC12192-12CTIL</org_study_id>
    <nct_id>NCT01681823</nct_id>
  </id_info>
  <brief_title>Effect of Modified Citrus Pectin on PSA Kinetics in Biochemical Relapsed PC With Serial Increases in PSA</brief_title>
  <official_title>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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>EcoNugenics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>EcoNugenics</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To determine if the oral administration of PectaSol-C Modified Citrus Pectin (MCP) is&#xD;
      effective at improving Prostate Specific Antigen (PSA) kinetics in men with biochemical&#xD;
      relapsed prostate cancer and serial increases in PSA levels. Also, documentation of any side&#xD;
      effects or benefits within parameter of the study is included.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study on the effect of PectaSol-C Modified Citrus Pectin (MCP) with subjects selected on&#xD;
      the basis of documented PC post local therapy, and biochemical relapse, with linear&#xD;
      progression of at least 3 PSA tests in at least 3 months. After initial screening, treatment&#xD;
      {4.8 grams (6 capsules) three times a day away from meals} will continue for 6 months&#xD;
      provided patients are showing benefit and tolerating the therapy well. Patient tolerability&#xD;
      of MCP will be assessed by comparing the results of monthly self-assessment diaries with&#xD;
      baseline assessments.&#xD;
&#xD;
      Prostate cancer is the most common cancer among men, except for non melanoma skin cancer. It&#xD;
      is the second leading cause of cancer related death in men. About 33% of prostate cancer&#xD;
      patients treated with primary therapy (surgery or radiation) will recur in the form of non&#xD;
      metastatic biochemically relapsed prostate cancer (BRPC-M0). In these patients, PSA is rising&#xD;
      while scans are negative for metastasis. Recent surveys demonstrated that approximately 40%&#xD;
      of prostate cancer patients use various complementary and alternative medicine modalities as&#xD;
      a component of therapy. Currently, there is no standard treatment for biochemical failure&#xD;
      with proven benefits. Patients are being encouraged to enroll in clinical trials to help&#xD;
      establish standards of care. Studies have shown that in 80% of patients with BRPC-M0, PSA&#xD;
      will rise by at least 25% every 6 months.&#xD;
&#xD;
      Native pectin is a complex carbohydrate soluble fiber. Dietary fibers, such as pectin, have&#xD;
      been shown to have positive effects on a wide spectrum of pathological conditions. Their&#xD;
      positive influence on human health is explained by their antioxidative, hypocholesterolemic,&#xD;
      and anticancer effects. MCP is composed of short, slightly-branched, carbohydrate chains&#xD;
      derived from the soluble albedo fraction of citrus fruit peels, which have been altered by&#xD;
      decreasing the molecular weight and degree of esterification using pH, temperature, and a&#xD;
      controlled enzymatic process. This specific modification is critical as it allows for the&#xD;
      absorption of MCP into the circulatory system and ensures its targeted bioactivity throughout&#xD;
      the body. MCP is relatively rich in galactose and thus antagonizes the binding protein&#xD;
      galectin-3 which results in suppression of cancer cell aggregation, adhesion, and metastasis.&#xD;
      MCP acts as a ligand for galectin-3, which plays a major role in tumor formation and&#xD;
      progression. It has been shown using a combination of fluorescence microscopy, flow&#xD;
      cytometry, and atomic force microscopy, that pectin galactan specifically binds to the&#xD;
      recombinant form of human galectin-3.&#xD;
&#xD;
      MCP showed anti-metastatic effects on cancer cells in multiple in vitro and in vivo studies.&#xD;
      MCP inhibits carbohydrate mediated tumor growth, angiogenesis and metastasis via effects on&#xD;
      galectin-3 function as demonstrated in an animal study on MCP's inhibition of breast and&#xD;
      colon cancer progression. Results demonstrated a 70.2% reduction in breast tumor growth, a&#xD;
      66% reduction in breast angiogenesis, and 0% breast to lung metastasis compared to 100% in&#xD;
      the control group; 0% colon to liver metastasis compared to 60% in the control group; and 25%&#xD;
      colon to lymph metastasis compared to 100% in the control group. In an earlier study oral&#xD;
      intake of MCP had been shown to act as a potent inhibitor of spontaneous prostate carcinoma&#xD;
      metastasis in an animal model, demonstrating a significant 56% reduction in lung metastases.&#xD;
      Human cancer cell lines (LNCaP androgen dependent &amp; PC3 androgen independent) and mouse&#xD;
      prostate cancer cell lines (CASP2-1 androgen dependent and CASP1-1 androgen independent)&#xD;
      treated with 1% MCP showed the following cytotoxicity due to induced apoptosis: 52.28% in&#xD;
      LNCaP; 48.16% in PC3; 23.03% in CASP2-1; and 49.01% in CASP1-1.13 The effects of MCP on&#xD;
      cell-cell and cell-matrix interactions mediated by carbohydrate-recognition were investigated&#xD;
      by looking at MCP-inhibited B16-F1 melanoma cells adhesion and aggregation. MCP was shown to&#xD;
      inhibit anchorage-independent growth of B16-F1 cells. These results indicate that&#xD;
      carbohydrate-recognition by cell surface galectin-3 is involved in cell-extracellular matrix&#xD;
      interaction and plays a role in anchorage-independent growth as well as the in vivo&#xD;
      embolization of tumor cells. The modulation of the lung colonization of B16-F1 melanoma cells&#xD;
      by MCP was first observed in 1992 when injection of MCP significantly decreased B16-F1&#xD;
      experimental metastasis (greater than 90%). Galectin-3 participation in the adhesion of the&#xD;
      MDA-MB-435 cells to the endothelium was observed by the clustering of galectin-3 on&#xD;
      endothelial cells at the sites of the contact with tumor cells, suggesting its potential&#xD;
      functional significance for anti-adhesive therapy of cancer metastasis. The anti-metastatic&#xD;
      effect of MCP has also been shown in reduced liver metastasis in a dose-dependent manner. The&#xD;
      use of MCP in combination with the chemotherapy drug doxorubicin has demonstrated an&#xD;
      increased cytotoxicity effect of inducing rapid cell death in prostate cancer cell lines&#xD;
      DU-145 (androgen independent) through apoptosis, and in LNCaP (androgen dependant) through&#xD;
      cell cycle arrest (G2-M arrest). These results show promise for the use of MCP with&#xD;
      doxorubicin as an adjuvant to chemotherapy which may allow for lower dosage of the cancer&#xD;
      drug to be used with less toxicity. A human clinical pilot trial with MCP showed an increase&#xD;
      in prostate specific antigen doubling time, a marker of slowing the progression of prostate&#xD;
      cancer. Clinical research on MCP also demonstrated a significant improvement in quality of&#xD;
      life and stabilization of disease for patients with advanced solid tumors.&#xD;
&#xD;
      In addition to its therapeutic roles against cancer, MCP has been shown to remove toxic&#xD;
      metals from the body without affecting essential minerals. In a clinical study, baseline&#xD;
      levels of heavy metals and essential minerals were established with 24-hours urine collection&#xD;
      prior to oral administration of MCP. 24-hours urine collection was repeated on days 1 and 6.&#xD;
      Urinary excretion of lead, mercury, cadmium, and arsenic increased significantly, essential&#xD;
      minerals were not changed significantly and no side effects were reported. In a hospital&#xD;
      study in China, children with lead toxicity were given MCP. Their blood serum levels went&#xD;
      down while corresponding lead levels in their urine increased significantly, without side&#xD;
      effects.&#xD;
&#xD;
      MCP has immunostimulatory properties as demonstrated in human blood samples, including the&#xD;
      activation of functional NK cells against K562 leukemic cells in culture: Unsaturated&#xD;
      oligogalacturonic acids appear to be the immunostimulatory carbohydrates in MCP. Human blood&#xD;
      samples collected from healthy volunteers were incubated with increasing concentrations of&#xD;
      MCP and antibodies. After 24-hours, blood-antibody mix was lysed and run on a flow cytometer&#xD;
      using a 3-color protocol and the % of activated T-cytotoxic cell subset, B-cell, and&#xD;
      NK-cells, and % increase over untreated control calculated and a significant dose dependent&#xD;
      activation was seen. The ability of the activated NK cells to induce leukemia cell death was&#xD;
      analyzed by co-incubating MCP-treated lymphocytes with K562 T-cell leukemia cells and induced&#xD;
      leukemia cell death was determined to be greater than 50%.&#xD;
&#xD;
      MCP has been demonstrated to be protective in experimental nephropathy with modulation of&#xD;
      early proliferation and later galectin-3 expression, apoptosis and fibrosis by experimentally&#xD;
      modulating galectin-3 in folic acid (FA)-induced acute kidney injury. Mice were pre-treated&#xD;
      with normal or 1% MCP-supplemented drinking water one week before FA injection. During the&#xD;
      initial injury phase, all FA treated mice lost weight whilst their kidneys enlarged secondary&#xD;
      to the renal insult; these gross changes were significantly lessened in the MCP group but&#xD;
      this was not associated with significant changes in galectin-3 expression. At a histological&#xD;
      level, MCP clearly reduced renal cell proliferation but did not affect apoptosis. Later,&#xD;
      during the recovery phase at two weeks, MCP-treated mice demonstrated reduced galectin-3 in&#xD;
      association with decreased renal fibrosis, macrophages, proinflammatory cytokine expression&#xD;
      and apoptosis. Galectin-3 inhibition by MCP was demonstrated to block Aldosterone (Aldo)&#xD;
      induced collagen type I synthesis. Rats were treated with Aldo-salt combined MCP for 3 weeks.&#xD;
      Hypertensive Aldo-treated rats presented vascular hypertrophy, inflammation, fibrosis, and&#xD;
      increased aortic Gal-3 expression. MCP treatment reversed all the above effects.&#xD;
&#xD;
      MCP is affirmed as GRAS (generally regarded as safe) under the US Code of Federal Regulation&#xD;
      21CFR184.1588.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2013</start_date>
  <completion_date type="Actual">January 2020</completion_date>
  <primary_completion_date type="Actual">January 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <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).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Prostate Specific Antigen (PSA) kinetics in men with biochemical relapsed prostate cancer and serial increases in PSA levels.</measure>
    <time_frame>6 month endpoint.</time_frame>
    <description>PSA doubling time increase will be used to show effectiveness of the Modified Citrus pectin (MCP).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>An assessment of adverse side effects due to Modified Citrus Pectin (MCP).</measure>
    <time_frame>6 month endpoint.</time_frame>
    <description>Patient tolerability of MCP will be assessed by comparing the results of weekly self-assessment diaries with baseline assessments.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Blood Serum Analysis (Galectin-3, C-Reactive Protein, Lipid Panels)</measure>
    <time_frame>6 month endpoint.</time_frame>
    <description>At baseline (0 month), and end of study (6 month): Blood draw for serum levels of galectin-3, C-reactive protein, and lipid panel.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Prostatic Neoplasms</condition>
  <arm_group>
    <arm_group_label>PectaSol-C Modified Citrus Pectin (MCP)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment with 4.8 grams PectaSol-C Modified Citrus Pectin three times a day, away from meals for six months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>PectaSol-C Modified Citrus Pectin (MCP)</intervention_name>
    <description>Oral administration of PectaSol-C MCP (4.8 grams in six capsules three times a day away from food).</description>
    <arm_group_label>PectaSol-C Modified Citrus Pectin (MCP)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Documented PC post local therapy with undetectable Prostate Specific Antigen (PSA),&#xD;
             and biochemical relapse (defined as post-surgery PSA &gt; 0.2 ng/ml; post-radiation &gt;&#xD;
             nadir +2 ng/ml, the PSA nadir is the lowest PSA reading achieved after treatment),&#xD;
             with linear progression of at least 3 PSA tests in at least 3 months before the&#xD;
             commencement of the trial.&#xD;
&#xD;
          -  All patients must have negative bone scan and CT scan for the chest-abdomen-pelvis&#xD;
             within 2 weeks prior to study initiation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Psychological, familial, sociological or geographical conditions that may interfere&#xD;
             with compliance with the study or prevent completion or compliance of protocol.&#xD;
&#xD;
          -  Other severe or poorly controlled medical condition(s).&#xD;
&#xD;
          -  Known allergies to any of the ingredients.&#xD;
&#xD;
          -  Hormonal therapy or other therapy for PC in the last 3 months.&#xD;
&#xD;
          -  Positive bone scan or CT scan of the chest-abdomen-pelvis.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Daniel Keizman, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Genitourinary Oncology Service, Institute of Oncology, Meir Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Isaac Eliaz, MD, LAc, MS</last_name>
    <role>Study Director</role>
    <affiliation>Amitabha Medical Clinic and Healing Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Moshe Frenkel, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Clinical Associate Professor, University of Texas</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Genitourinary Oncology Service, Institute of Oncology, Meir Medical Center, Tshernichovsky 59,</name>
      <address>
        <city>Kfar-Saba</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
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    <citation>Keizman D, Maimon N, Gottfried M. Metastatic hormone refractory prostate cancer: recent advances in standard treatment paradigm, and future directions. Am J Clin Oncol. 2014 Jun;37(3):289-96. doi: 10.1097/COC.0b013e318248dc1e.</citation>
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    <citation>Antonarakis ES, Zahurak ML, Lin J, Keizman D, Carducci MA, Eisenberger MA. Changes in PSA kinetics predict metastasis- free survival in men with PSA-recurrent prostate cancer treated with nonhormonal agents: combined analysis of 4 phase II trials. Cancer. 2012 Mar 15;118(6):1533-42. doi: 10.1002/cncr.26437.</citation>
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    <citation>Nangia-Makker P, Conklin J, Hogan V, Raz A. Carbohydrate-binding proteins in cancer, and their ligands as therapeutic agents. Trends Mol Med. 2002 Apr;8(4):187-92. doi: 10.1016/s1471-4914(02)02295-5.</citation>
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    <citation>Yan J, Katz A. PectaSol-C modified citrus pectin induces apoptosis and inhibition of proliferation in human and mouse androgen-dependent and- independent prostate cancer cells. Integr Cancer Ther. 2010 Jun;9(2):197-203. doi: 10.1177/1534735410369672. Epub 2010 May 11.</citation>
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    <citation>Kolatsi-Joannou M, Price KL, Winyard PJ, Long DA. Modified citrus pectin reduces galectin-3 expression and disease severity in experimental acute kidney injury. PLoS One. 2011 Apr 8;6(4):e18683. doi: 10.1371/journal.pone.0018683.</citation>
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    <citation>Ramachandran C, Wilk BJ, Hotchkiss A, Chau H, Eliaz I, Melnick SJ. Activation of human T-helper/inducer cell, T-cytotoxic cell, B-cell, and natural killer (NK)-cells and induction of natural killer cell activity against K562 chronic myeloid leukemia cells with modified citrus pectin. BMC Complement Altern Med. 2011 Aug 4;11:59. doi: 10.1186/1472-6882-11-59.</citation>
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    <citation>Liu HY, Huang ZL, Yang GH, Lu WQ, Yu NR. Inhibitory effect of modified citrus pectin on liver metastases in a mouse colon cancer model. World J Gastroenterol. 2008 Dec 28;14(48):7386-91. doi: 10.3748/wjg.14.7386.</citation>
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    <citation>Glinsky VV, Raz A. Modified citrus pectin anti-metastatic properties: one bullet, multiple targets. Carbohydr Res. 2009 Sep 28;344(14):1788-91. doi: 10.1016/j.carres.2008.08.038. Epub 2008 Sep 26.</citation>
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    <citation>Dange MC, Srinivasan N, More SK, Bane SM, Upadhya A, Ingle AD, Gude RP, Mukhopadhyaya R, Kalraiya RD. Galectin-3 expressed on different lung compartments promotes organ specific metastasis by facilitating arrest, extravasation and organ colonization via high affinity ligands on melanoma cells. Clin Exp Metastasis. 2014 Aug;31(6):661-73. doi: 10.1007/s10585-014-9657-2. Epub 2014 Jun 21.</citation>
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  <verification_date>January 2020</verification_date>
  <study_first_submitted>September 6, 2012</study_first_submitted>
  <study_first_submitted_qc>September 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2012</study_first_posted>
  <last_update_submitted>January 27, 2020</last_update_submitted>
  <last_update_submitted_qc>January 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 29, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Prostate Cancer</keyword>
  <keyword>Prostatic Neoplasms</keyword>
  <keyword>Prostate Specific Antigen</keyword>
  <keyword>Modified Citrus Pectin</keyword>
  <keyword>PectaSol-C</keyword>
  <keyword>Biochemical Relapse</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01681823
org study id: MMC12192-12CTIL
nct id: NCT01681823
lead sponsor: 
has dmc: Yes
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.
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.
allocation: N/A
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).
primary purpose: Treatment
masking: None (Open Label)
measure: Prostate Specific Antigen (PSA) kinetics in men with biochemical relapsed prostate cancer and serial increases in PSA levels.
time frame: 6 month endpoint.
description: PSA doubling time increase will be used to show effectiveness of the Modified Citrus pectin (MCP).
measure: An assessment of adverse side effects due to Modified Citrus Pectin (MCP).
time frame: 6 month endpoint.
description: Patient tolerability of MCP will be assessed by comparing the results of weekly self-assessment diaries with baseline assessments.
measure: Blood Serum Analysis (Galectin-3, C-Reactive Protein, Lipid Panels)
time frame: 6 month endpoint.
description: At baseline (0 month), and end of study (6 month): Blood draw for serum levels of galectin-3, C-reactive protein, and lipid panel.
arm group label: PectaSol-C Modified Citrus Pectin (MCP)
arm group type: Experimental
description: Treatment with 4.8 grams PectaSol-C Modified Citrus Pectin three times a day, away from meals for six months.
intervention type: Dietary Supplement
intervention name: PectaSol-C Modified Citrus Pectin (MCP)
description: Oral administration of PectaSol-C MCP (4.8 grams in six capsules three times a day away from food).
arm group label: PectaSol-C Modified Citrus Pectin (MCP)
criteria: 
gender: Male
minimum age: 21 Years
maximum age: N/A
healthy volunteers: No
last name: Daniel Keizman, MD
role: Principal Investigator
affiliation: Genitourinary Oncology Service, Institute of Oncology, Meir Medical Center
last name: Isaac Eliaz, MD, LAc, MS
role: Study Director
affiliation: Amitabha Medical Clinic and Healing Center
last name: Moshe Frenkel, MD
role: Study Chair
affiliation: Clinical Associate Professor, University of Texas
facility: 
country: Israel
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PMID: 22772426
citation: Antonarakis ES, Zahurak ML, Lin J, Keizman D, Carducci MA, Eisenberger MA. Changes in PSA kinetics predict metastasis- free survival in men with PSA-recurrent prostate cancer treated with nonhormonal agents: combined analysis of 4 phase II trials. Cancer. 2012 Mar 15;118(6):1533-42. doi: 10.1002/cncr.26437.
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PMID: 11927277
citation: Yan J, Katz A. PectaSol-C modified citrus pectin induces apoptosis and inhibition of proliferation in human and mouse androgen-dependent and- independent prostate cancer cells. Integr Cancer Ther. 2010 Jun;9(2):197-203. doi: 10.1177/1534735410369672. Epub 2010 May 11.
PMID: 20462856
citation: Kolatsi-Joannou M, Price KL, Winyard PJ, Long DA. Modified citrus pectin reduces galectin-3 expression and disease severity in experimental acute kidney injury. PLoS One. 2011 Apr 8;6(4):e18683. doi: 10.1371/journal.pone.0018683.
PMID: 21494626
citation: Ramachandran C, Wilk BJ, Hotchkiss A, Chau H, Eliaz I, Melnick SJ. Activation of human T-helper/inducer cell, T-cytotoxic cell, B-cell, and natural killer (NK)-cells and induction of natural killer cell activity against K562 chronic myeloid leukemia cells with modified citrus pectin. BMC Complement Altern Med. 2011 Aug 4;11:59. doi: 10.1186/1472-6882-11-59.
PMID: 21816083
citation: Jiang J, Eliaz I, Sliva D. Synergistic and additive effects of modified citrus pectin with two polybotanical compounds, in the suppression of invasive behavior of human breast and prostate cancer cells. Integr Cancer Ther. 2013 Mar;12(2):145-52. doi: 10.1177/1534735412442369. Epub 2012 Apr 24.
PMID: 22532035
citation: Liu HY, Huang ZL, Yang GH, Lu WQ, Yu NR. Inhibitory effect of modified citrus pectin on liver metastases in a mouse colon cancer model. World J Gastroenterol. 2008 Dec 28;14(48):7386-91. doi: 10.3748/wjg.14.7386.
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citation: Glinsky VV, Raz A. Modified citrus pectin anti-metastatic properties: one bullet, multiple targets. Carbohydr Res. 2009 Sep 28;344(14):1788-91. doi: 10.1016/j.carres.2008.08.038. Epub 2008 Sep 26.
PMID: 19061992
citation: Zhao ZY, Liang L, Fan X, Yu Z, Hotchkiss AT, Wilk BJ, Eliaz I. The role of modified citrus pectin as an effective chelator of lead in children hospitalized with toxic lead levels. Altern Ther Health Med. 2008 Jul-Aug;14(4):34-8. Erratum In: Altern Ther Health Med. 2008 Nov-Dec;14(6):18.
PMID: 18616067
citation: Eliaz I, Weil E, Wilk B. Integrative medicine and the role of modified citrus pectin/alginates in heavy metal chelation and detoxification--five case reports. Forsch Komplementmed. 2007 Dec;14(6):358-64. doi: 10.1159/000109829. Epub 2007 Dec 12.
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PMID: 17786185
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PMID: 14663471
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PMID: 24460334
responsible party type: Sponsor
mesh term: Prostatic Neoplasms