Muscadine Plus (MPX) In Men With Prostate Cancer
Condition: Adenocarcinoma of the Prostate
MeSH terms: Adenocarcinoma
Intervention: Muscadine Plus; Placebos
Intervention description: Ellagic acid inhibits DNA Methyltransferase. DNA Methyltransferases (DNMTs) are a family of enzymes that regulate chromatin methylation and use S-adenosyl methionine (SAM) as the methyl donor. Ellagic acid's metabolite, urolithin-A inhibits the protein complex nuclear factor kappa-light-enhancer of activated B-cells (NFkB), potentially leading to increased rates of apoptosis and decreases in cancer cell proliferation. Extracts from Vitis rotundifolia have shown inhibition of the phosphatidylinositol 3-kinase-Akt pathway.; The placebo capsules are rice flour that will be placed in white opaque capsules identical to the ones used for MPX.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This is a multicenter, double-blind, randomized study to evaluate the benefit of MPX supplementation in the subset of men who display the Alanine/Alanine SOD2 genotype of MnSOD. Based on a previous randomized phase II trial of MPX at Hopkins, PSA doubling time (PSA-DT) was prolonged in this subgroup of men.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 59.0
Sex: Male
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No

Summary:

      This research is being done to determine if men with rising PSA after initial therapy for
      localized prostate cancer who display the Alanine/Alanine SOD2 genotype of MnSOD and
      supplement their diet with MPX have greater decrease in PSA slope following treatment
      compared to men that do not supplement with MPX.
    

Eligibility criteria:

        Inclusion Criteria:

        Patients meeting the following conditions are eligible for registration and participation
        in the study:

          1. Subject has histologically or cytologically confirmed adenocarcinoma of the prostate

          2. Subject has undergone definitive treatment (surgery, surgery with radiation therapy,
             cryotherapy, radiation therapy or brachytherapy) for the primary prostate tumor (prior
             chemotherapy is not allowed) .

             a. A subject with a rising PSA post-prostatectomy should consider radiation as a
             potentially curative alternative. If subject declines radiation or is not a candidate
             for radiation, he may be considered eligible in this setting.

          3. Subject has a rising PSA on a minimum of 3 time points (2 rises) within the 12 months
             prior to study initiation (this will include the PSA measurement taken at the
             screening visit, but not at the baseline day 0 study visit).

             For purposes of calculating PSA doubling time (PSADT):

               1. All PSA values used in the calculation should be ≥ 0.20 ng/ml and overall should
                  follow a rising trend;

               2. Record every available PSA drawn within the last 12 months of the most recent
                  local PSA;

               3. The minimum requirement is 3 PSA values obtained over 3 months with a minimum of
                  4 weeks between measurements;

               4. If there are 4 or more PSAs available, the time interval between the first and
                  last PSA measurements must be at least 3 months, and, there is no minimum time
                  interval requirement between any two PSA measurements;

               5. For radiotherapy only patients, record PSA nadir value and collection date. PSADT
                  (PSA doubling time) must be positive according to Memorial Sloan Kettering Cancer
                  Center Prostate Cancer Nomograms under this link:
                  http://www.mskcc.org/applications/nomograms/prostate/PsaDoublingTime.aspx

          4. One of the following criteria must be met.

               1. Absolute level of PSA >0.4 ng/mL following surgery. (surgery only)

               2. Absolute level of PSA >0.4 ng/mL for subjects treated with multiple treatment
                  modalities (e.g., surgery + radiation, surgery + cryotherapy, etc.).

               3. A rise by 2 ng/mL or more above the nadir PSA will be considered the standard
                  definition for biochemical failure after radiation therapy with or without
                  hormonal therapy. (radiation only)

          5. Subject is >18 years of age.

          6. Subject has life expectancy of greater than 12 months.

          7. Subject has Eastern Cooperative Oncology Group performance status 0, 1 or 2

          8. Subject has testosterone level of ≥1.5 ng/mL at screening.

          9. Subject has normal organ and marrow function as defined below:

               1. Leukocytes >3,000/microliter

               2. absolute neutrophil count >1,500/microliter

               3. platelets >100,000/microliter

               4. total bilirubin <1.5 x upper limit of normal except for Gilberts <2.5 x upper
                  limit of normal

               5. aspartate aminotransferase/Alanine transaminase ≤ 2.5 X upper limit of normal

               6. creatinine ≤ 2.5 upper limit of normal

         10. Subject agrees to abstain from other commercially available MuscadinePlus (MP)
             products (Vinetra, MuscadinePlus or MP capsules) while participating in this study.

         11. Subject's use of other dietary/herbal supplements (e.g. saw palmetto, selenium,
             pomegranate juice or pills, acai concentrated extract, etc) has been stable for at
             least 2 months prior to screening and the subject agrees not to stop or change the
             dose(s) while participating in the study.

         12. Subject has signed a written informed consent document and agrees to comply with
             requirements of the study.

         13. CT or MRI chest/abdomen/pelvis and bone scan without evidence of metastatic disease as
             an inclusion.

         14. Subject agrees to genotyping of manganese-dependent superoxide dismutase 2 (MnSOD2)
             gene and any genetic counseling. Only those with Alanine/Alanine SOD2 genotype will be
             randomized.

        Exclusion Criteria:

        Subjects meeting the following conditions are not eligible for participation in the study:

          1. Subject has known radiographic evidence of metastatic disease, except for presence of
             positive lymph nodes from the surgical pathology. Pelvic/intraperitoneal lymph nodes
             less than 1.5 cm maybe considered nonspecific and the patient would be eligible. If
             there is any clinical suspicion for metastatic disease, CT and Bone Scan must be
             performed to rule out metastatic disease, within the last four months, per standard of
             care.

          2. Subject has received any therapies that modulate testosterone levels (e.g., androgen
             ablative/anti-androgen therapy, 5 alpha reductase inhibitors) for a minimum of 12
             months prior to study.

          3. Subject has had prior or concomitant treatment with experimental drugs, high dose
             steroids, or any other cancer treatment within 4 weeks prior to the first dose of the
             study product.

          4. Subject has consumed any Muscadine Plus over the past 2 months.

          5. Subject has a known allergy to muscadine grapes, ellagic acid or rice

          6. Subject has uncontrolled concurrent illness including, but not limited to, ongoing or
             active infection, symptomatic congestive heart failure, unstable angina pectoris,
             cardiac arrhythmia, or psychiatric illness/social situations that would limit
             compliance with study requirements.

          7. Subject has negative PSA doubling time (negative doubling time corresponds with
             decreasing PSA) Doubling time may be computed using the Sloan Kettering prediction
             tools posted at
             http://www.mskcc.org/applications/nomograms/prostate/PsaDoublingTime.aspx