Muscadine Plus (MPX) In Men With Prostate Cancer

• ClinicalTrials.gov Identifier: NCT03535675
• Recruitment Status: Terminated
• First Posted: May 24, 2018
• Results First Posted: May 22, 2023
• Last Update Posted: May 22, 2023
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborator: Greater Washington Community Foundation
• Information provided by (Responsible Party): Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Adenocarcinoma of the Prostate
• Interventions: Drug: Muscadine Plus; Drug: Placebos
• Enrollment: 59

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Muscadine Plus	Placebo
Arm/Group Description	Each treatment cycle consists of once daily oral dosing of 4000 mg Muscadine Plus, every day throughout each 12 week (84 day) cycle. Patients may continue to receive additional cycles of study drug and will be followed every three months with standard visits with their physician until completion of 48 weeks of study treatment, disease progression, or until they wish to discontinue the drug. Muscadine Plus: 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.	Each treatment cycle consists of once daily oral dosing of 4000 mg placebos, every day throughout each 12 week (84 day) cycle. Patients may continue to receive additional cycles of placebo and will be followed every three months with standard visits with their physician until completion of 48 weeks of study treatment, disease progression, or until they wish to discontinue the drug. Placebos: The placebo capsules are rice flour that will be placed in white opaque capsules identical to the ones used for MPX.
Period Title: Overall Study
Started	29	30
Completed	29	30
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Muscadine Plus	Placebo	Total
Arm/Group Description		Each treatment cycle consists of once daily oral dosing of 4000 mg Muscadine Plus, every day throughout each 12 week (84 day) cycle. Patients may continue to receive additional cycles of study drug and will be followed every three months with standard visits with their physician until completion of 48 weeks of study treatment, disease progression, or until they wish to discontinue the drug. Muscadine Plus: 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.	Each treatment cycle consists of once daily oral dosing of 4000 mg placebos, every day throughout each 12 week (84 day) cycle. Patients may continue to receive additional cycles of placebo and will be followed every three months with standard visits with their physician until completion of 48 weeks of study treatment, disease progression, or until they wish to discontinue the drug. Placebos: The placebo capsules are rice flour that will be placed in white opaque capsules identical to the ones used for MPX.	Total of all reporting groups
Overall Number of Baseline Participants		29	30	59
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	29 participants	30 participants	59 participants
		75; (60 to 92)	73; (53 to 83)	74; (53 to 92)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	29 participants	30 participants	59 participants
	Female	0 0.0%	0 0.0%	0 0.0%
	Male	29 100.0%	30 100.0%	59 100.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	29 participants	30 participants	59 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	2 6.9%	0 0.0%	2 3.4%
	White	26 89.7%	28 93.3%	54 91.5%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	1 3.4%	2 6.7%	3 5.1%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	29 participants	30 participants	59 participants
		29 100.0%	30 100.0%	59 100.0%
Pre-study PSA slope [1]; Median (Inter-Quartile Range); Unit of measure: ng/mL/Month
	Number Analyzed	29 participants	30 participants	59 participants
		0.11; (0.03 to 0.29)	0.1; (0.03 to 0.44)	0.1; (0.03 to 0.44)
		[1] Measure Description: Pre-study PSA slope was calculated using all available PSA measurements in the 12 months prior to enrollment, including screening PSA measurement. An analysis of covariance (ANCOVA) was used to assess the difference in MPX and placebo treatment effects, with on-study PSA slope as the independent variable and treatment arm and pre-study PSA slope covariates. The unit of measure for PSA slope is ng/mL/Month.

Outcome Measures

1. Primary Outcome

Title	Prostate Specific Antigen (PSA) Response
Description	To determine if men who display the Alanine/Alanine superoxide dismutase 2 (SOD2) genotype of MnSOD and supplement their diet with MPX have greater changes in PSA slope following treatment compared to men that do not supplement with MPX. PSA response will be measured as the change of serum PSA in ng/mL/month, on-study PSA slope for each patient with comparisons between treatment arms adjusted for pre-study PSA slope; on-study PSA slope was calculated from PSA values taken at baseline,12, 24, 36, and 48 weeks, and calculated as the slope of the simple linear regression of the natural log of PSA versus time in ng/mL/month.
Time Frame	baseline,12, 24, 36, and 48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Muscadine Plus	Placebo
Arm/Group Description:	Each treatment cycle consists of once daily oral dosing of 4000 mg Muscadine Plus, every day throughout each 12 week (84 day) cycle. Patients may continue to receive additional cycles of study drug and will be followed every three months with standard visits with their physician until completion of 48 weeks of study treatment, disease progression, or until they wish to discontinue the drug. Muscadine Plus: 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.	Each treatment cycle consists of once daily oral dosing of 4000 mg placebos, every day throughout each 12 week (84 day) cycle. Patients may continue to receive additional cycles of placebo and will be followed every three months with standard visits with their physician until completion of 48 weeks of study treatment, disease progression, or until they wish to discontinue the drug. Placebos: The placebo capsules are rice flour that will be placed in white opaque capsules identical to the ones used for MPX.
Overall Number of Participants Analyzed	29	30
Mean (95% Confidence Interval); Unit of Measure: ng/mL/Month
	0.106; (0.08 to 0.13)	0.089; (0.06 to 0.11)

2. Secondary Outcome

Title	PSA Doubling Time
Description	PSA doubling time (PSADT) will be calculated in months by measuring the PSA values within 12 months from start of intervention.
Time Frame	Up to 26 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Muscadine Plus	Placebo
Arm/Group Description:	Each treatment cycle consists of once daily oral dosing of 4000 mg Muscadine Plus, every day throughout each 12 week (84 day) cycle. Patients may continue to receive additional cycles of study drug and will be followed every three months with standard visits with their physician until completion of 48 weeks of study treatment, disease progression, or until they wish to discontinue the drug. Muscadine Plus: 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.	Each treatment cycle consists of once daily oral dosing of 4000 mg placebos, every day throughout each 12 week (84 day) cycle. Patients may continue to receive additional cycles of placebo and will be followed every three months with standard visits with their physician until completion of 48 weeks of study treatment, disease progression, or until they wish to discontinue the drug. Placebos: The placebo capsules are rice flour that will be placed in white opaque capsules identical to the ones used for MPX.
Overall Number of Participants Analyzed	29	30
Median (Full Range); Unit of Measure: months
	6.56; (2.39 to 20.82)	6.87; (1.57 to 25.48)

3. Secondary Outcome

Title	PSA Objective Response Rate
Description	The number of patients with a decrease in PSA of ≥50%
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Muscadine Plus	Placebo
Arm/Group Description:	Each treatment cycle consists of once daily oral dosing of 4000 mg Muscadine Plus, every day throughout each 12 week (84 day) cycle. Patients may continue to receive additional cycles of study drug and will be followed every three months with standard visits with their physician until completion of 48 weeks of study treatment, disease progression, or until they wish to discontinue the drug. Muscadine Plus: 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.	Each treatment cycle consists of once daily oral dosing of 4000 mg placebos, every day throughout each 12 week (84 day) cycle. Patients may continue to receive additional cycles of placebo and will be followed every three months with standard visits with their physician until completion of 48 weeks of study treatment, disease progression, or until they wish to discontinue the drug. Placebos: The placebo capsules are rice flour that will be placed in white opaque capsules identical to the ones used for MPX.
Overall Number of Participants Analyzed	29	30
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%

4. Secondary Outcome

Title	PSA Progression
Description	The time to disease progression for both treatment groups by PSA progression. PSA progression is defined as an increase in PSA greater than 50% and >5 ng/ml above nadir.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Muscadine Plus	Placebo
Arm/Group Description:	Each treatment cycle consists of once daily oral dosing of 4000 mg Muscadine Plus, every day throughout each 12 week (84 day) cycle. Patients may continue to receive additional cycles of study drug and will be followed every three months with standard visits with their physician until completion of 48 weeks of study treatment, disease progression, or until they wish to discontinue the drug. Muscadine Plus: 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.	Each treatment cycle consists of once daily oral dosing of 4000 mg placebos, every day throughout each 12 week (84 day) cycle. Patients may continue to receive additional cycles of placebo and will be followed every three months with standard visits with their physician until completion of 48 weeks of study treatment, disease progression, or until they wish to discontinue the drug. Placebos: The placebo capsules are rice flour that will be placed in white opaque capsules identical to the ones used for MPX.
Overall Number of Participants Analyzed	29	30
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (NA to NA)	13.77 [2]; (11.24 to NA)

[1]

The median had not been reached in the MPX arm at the time of the analysis.

[2]

The upper limit of confidence interval was not reached.at the time of analysis.

5. Secondary Outcome

Title	Radiographic Progression
Description	The time to disease progression for both treatment groups by radiologic disease progression (i.e. development of metastatic disease).
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Muscadine Plus	Placebo
Arm/Group Description:	Each treatment cycle consists of once daily oral dosing of 4000 mg Muscadine Plus, every day throughout each 12 week (84 day) cycle. Patients may continue to receive additional cycles of study drug and will be followed every three months with standard visits with their physician until completion of 48 weeks of study treatment, disease progression, or until they wish to discontinue the drug. Muscadine Plus: 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.	Each treatment cycle consists of once daily oral dosing of 4000 mg placebos, every day throughout each 12 week (84 day) cycle. Patients may continue to receive additional cycles of placebo and will be followed every three months with standard visits with their physician until completion of 48 weeks of study treatment, disease progression, or until they wish to discontinue the drug. Placebos: The placebo capsules are rice flour that will be placed in white opaque capsules identical to the ones used for MPX.
Overall Number of Participants Analyzed	29	30
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (NA to NA)	NA [1]; (NA to NA)

[1]

There were only two events, so Radiographic progression-free survival (rPFS) could not be calculated.

Adverse Events

Time Frame	up to 2 years
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Muscadine Plus		Placebo
Arm/Group Description	Each treatment cycle consists of once daily oral dosing of 4000 mg Muscadine Plus, every day throughout each 12 week (84 day) cycle. Patients may continue to receive additional cycles of study drug and will be followed every three months with standard visits with their physician until completion of 48 weeks of study treatment, disease progression, or until they wish to discontinue the drug. Muscadine Plus: 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.		Each treatment cycle consists of once daily oral dosing of 4000 mg placebos, every day throughout each 12 week (84 day) cycle. Patients may continue to receive additional cycles of placebo and will be followed every three months with standard visits with their physician until completion of 48 weeks of study treatment, disease progression, or until they wish to discontinue the drug. Placebos: The placebo capsules are rice flour that will be placed in white opaque capsules identical to the ones used for MPX.
All-Cause Mortality
	Muscadine Plus		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/29 (0.00%)		0/30 (0.00%)
Serious Adverse Events
	Muscadine Plus		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/29 (3.45%)		6/30 (20.00%)
Cardiac disorders
Heart failure *	0/29 (0.00%)	0	1/30 (3.33%)	1
Pericarditis *	0/29 (0.00%)	0	2/30 (6.67%)	3
Gastrointestinal disorders
Small bowel obstruction *	1/29 (3.45%)	1	0/30 (0.00%)	0
General disorders
Fatigue *	0/29 (0.00%)	0	1/30 (3.33%)	1
Renal and urinary disorders
Urinary retention *	0/29 (0.00%)	0	1/30 (3.33%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea *	0/29 (0.00%)	0	1/30 (3.33%)	1
* Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	2%
	Muscadine Plus		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/29 (75.86%)		23/30 (76.67%)
Cardiac disorders
chest pain - cardiac *	0/29 (0.00%)	0	1/30 (3.33%)	1
sinus bradycardia *	0/29 (0.00%)	0	1/30 (3.33%)	1
Ear and labyrinth disorders
tinnitus *	1/29 (3.45%)	1	0/30 (0.00%)	0
Gastrointestinal disorders
flatulence *	1/29 (3.45%)	3	1/30 (3.33%)	3
constipation *	1/29 (3.45%)	2	0/30 (0.00%)	0
diarrhea *	1/29 (3.45%)	2	0/30 (0.00%)	0
dyspepsia *	1/29 (3.45%)	2	1/30 (3.33%)	1
abdominal pain *	1/29 (3.45%)	1	0/30 (0.00%)	0
dry mouth *	1/29 (3.45%)	1	0/30 (0.00%)	0
gastroesophageal reflux disease *	1/29 (3.45%)	1	0/30 (0.00%)	0
nausea *	1/29 (3.45%)	1	1/30 (3.33%)	1
rectal hemorrhage *	1/29 (3.45%)	1	0/30 (0.00%)	0
dysphagia *	0/29 (0.00%)	0	1/30 (3.33%)	1
General disorders
fatigue *	2/29 (6.90%)	4	2/30 (6.67%)	4
pain *	1/29 (3.45%)	2	0/30 (0.00%)	0
edema limbs *	1/29 (3.45%)	1	0/30 (0.00%)	0
non-cardiac chest pain *	1/29 (3.45%)	1	0/30 (0.00%)	0
localized edema *	0/29 (0.00%)	0	1/30 (3.33%)	1
Hepatobiliary disorders
portal vein thrombosis *	0/29 (0.00%)	0	1/30 (3.33%)	1
Immune system disorders
allergic reaction *	1/29 (3.45%)	1	0/30 (0.00%)	0
Infections and infestations
upper respiratory infection *	1/29 (3.45%)	2	0/30 (0.00%)	0
urinary tract infection *	1/29 (3.45%)	2	0/30 (0.00%)	0
herpes simplex reactivation *	1/29 (3.45%)	1	0/30 (0.00%)	0
shingles *	1/29 (3.45%)	1	0/30 (0.00%)	0
Injury, poisoning and procedural complications
fall *	0/29 (0.00%)	0	1/30 (3.33%)	1
Investigations
creatinine increased *	1/29 (3.45%)	2	1/30 (3.33%)	1
white blood cell decreased *	0/29 (0.00%)	0	2/30 (6.67%)	2
aspartate aminotransferase increased *	1/29 (3.45%)	1	1/30 (3.33%)	1
lymphocyte count decreased *	1/29 (3.45%)	1	0/30 (0.00%)	0
Metabolism and nutrition disorders
hypercalcemia *	1/29 (3.45%)	1	0/30 (0.00%)	0
hypophosphatemia *	1/29 (3.45%)	1	0/30 (0.00%)	0
hyperglycemia *	0/29 (0.00%)	0	1/30 (3.33%)	1
Musculoskeletal and connective tissue disorders
pain in extremity *	1/29 (3.45%)	3	1/30 (3.33%)	2
back pain *	0/29 (0.00%)	0	1/30 (3.33%)	2
generalized muscle weakness *	0/29 (0.00%)	0	1/30 (3.33%)	1
neck pain *	0/29 (0.00%)	0	1/30 (3.33%)	1
Nervous system disorders
dizziness *	0/29 (0.00%)	0	2/30 (6.67%)	2
headache *	1/29 (3.45%)	1	1/30 (3.33%)	2
peripheral motor neuropathy *	1/29 (3.45%)	1	1/30 (3.33%)	1
spasticity *	1/29 (3.45%)	1	0/30 (0.00%)	0
Renal and urinary disorders
dysuria *	1/29 (3.45%)	1	1/30 (3.33%)	3
hematuria *	1/29 (3.45%)	2	1/30 (3.33%)	2
urinary frequency *	1/29 (3.45%)	2	0/30 (0.00%)	0
urinary incontinence *	1/29 (3.45%)	1	0/30 (0.00%)	0
urinary urgency *	1/29 (3.45%)	1	0/30 (0.00%)	0
urine discoloration *	0/29 (0.00%)	0	1/30 (3.33%)	1
Respiratory, thoracic and mediastinal disorders
cough *	1/29 (3.45%)	1	0/30 (0.00%)	0
hypoxia *	1/29 (3.45%)	1	0/30 (0.00%)	0
rhinorrhea *	1/29 (3.45%)	1	0/30 (0.00%)	0
sore throat *	1/29 (3.45%)	1	0/30 (0.00%)	0
dyspnea *	0/29 (0.00%)	0	1/30 (3.33%)	1
epistaxis *	0/29 (0.00%)	0	1/30 (3.33%)	1
postnasal drip *	0/29 (0.00%)	0	1/30 (3.33%)	1
Skin and subcutaneous tissue disorders
pruritus *	0/29 (0.00%)	0	2/30 (6.67%)	2
eczema *	0/29 (0.00%)	0	1/30 (3.33%)	1
nail changes *	0/29 (0.00%)	0	1/30 (3.33%)	1
Vascular disorders
hot flashes *	0/29 (0.00%)	0	1/30 (3.33%)	1
* Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Channing Paller; M.D.
• Organization: Johns Hopkins University
• Phone: 4109558239
• EMail: cpaller1@jhmi.edu

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT03535675
• Other Study ID Numbers: J1823; IRB00166021 ( Other Identifier: JHM IRB )
• First Submitted: May 10, 2018
• First Posted: May 24, 2018
• Results First Submitted: April 3, 2023
• Results First Posted: May 22, 2023
• Last Update Posted: May 22, 2023