Trial Outcomes & Findings for Effects of Two Doses of MPX Capsules on Rising Prostate-specific Antigen Levels in Men Following Initial Therapy for Prostate Cancer (NCT NCT01317199)

Last Updated: 2021-04-02

Results Overview

To determine the recommended dosing for Muscadine Plus and to evaluate the safety and tolerability of Muscadine Plus in prostate cancer patients with rising PSA following definitive therapy.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

143 participants

Primary outcome timeframe

Up to 7 months post-intervention

Results posted on

2021-04-02

Participant Flow

Recruitment dates: Phase I: October 4, 2011-August 7, 2012 in medical clinics Phase II: January 31, 2013-October 20, 2014

Enrolled subjects agreed to abstain from other commercially available Muscadine Plus products while in this trial. If subjects were taking other dietary/herbal supplements (e.g. saw palmetto, selenium, pomegranate juice or pills, etc) prior to study entry, they had to be on a stable dose for 2 months prior and not stop while on trial.

Participant milestones

Participant milestones
Measure	Dose-escalation Phase:Muscadine Plus Grape Skin Extract (MPX) Muscadine Plus Grape Skin Extract: Phase I Dose-escalation starts at 500mg daily for 1 cycle (28 days), then increased to 1000mg for 2nd cycle, then increased to 2000mg daily for 3rd cycle, then increased to 3000mg daily for 4th cycle, then increased to maximum dose of 4000mg daily for final cycle. Pills given by mouth once daily for 28 days per cycle.	Phase 2: Placebo Control Randomly-assigned participants receive 8 capsules once daily of placebo composed of pulverized rice for up to 12 cycles (28 days per cycle).	Phase 2: Low-dose MPX Randomly-assigned participants receive one capsule of drug (500mg MPX) and seven capsules of placebo composed of pulverized rice, once daily for up to 12 cycles (28 days per cycle).	Phase 2: High-dose MPX Randomly-assigned participants receive 8 capsules of drug (4000mg MPX) once daily for up to 12 cycles (28 days per cycle).
Dose-escalation Phase 1 STARTED	14	0	0	0
Dose-escalation Phase 1 Cycle 1: 500mg MPX Once Daily for 28 Day	2	0	0	0
Dose-escalation Phase 1 Cycle 2: 1000mg MPX Daily for 28 Days	2	0	0	0
Dose-escalation Phase 1 Cycle 3: 2000mg MPX Daily for 28 Days	2	0	0	0
Dose-escalation Phase 1 Cycle 4: 3000mg MPX Daily for 28 Days	2	0	0	0
Dose-escalation Phase 1 Cycle 5: 4000mg MPX Daily for 28 Days	6	0	0	0
Dose-escalation Phase 1 COMPLETED	7	0	0	0
Dose-escalation Phase 1 NOT COMPLETED	7	0	0	0
Randomized Phase 2 STARTED	0	24	56	49
Randomized Phase 2 COMPLETED	0	13	35	32
Randomized Phase 2 NOT COMPLETED	0	11	21	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Dose-escalation Phase:Muscadine Plus Grape Skin Extract (MPX) Muscadine Plus Grape Skin Extract: Phase I Dose-escalation starts at 500mg daily for 1 cycle (28 days), then increased to 1000mg for 2nd cycle, then increased to 2000mg daily for 3rd cycle, then increased to 3000mg daily for 4th cycle, then increased to maximum dose of 4000mg daily for final cycle. Pills given by mouth once daily for 28 days per cycle.	Phase 2: Placebo Control Randomly-assigned participants receive 8 capsules once daily of placebo composed of pulverized rice for up to 12 cycles (28 days per cycle).	Phase 2: Low-dose MPX Randomly-assigned participants receive one capsule of drug (500mg MPX) and seven capsules of placebo composed of pulverized rice, once daily for up to 12 cycles (28 days per cycle).	Phase 2: High-dose MPX Randomly-assigned participants receive 8 capsules of drug (4000mg MPX) once daily for up to 12 cycles (28 days per cycle).
Dose-escalation Phase 1 Physician Decision	5	0	0	0
Dose-escalation Phase 1 Disease progression	1	0	0	0
Dose-escalation Phase 1 Comorbidities, myasthenia gravis	1	0	0	0
Randomized Phase 2 Disease progression	0	3	7	5
Randomized Phase 2 Withdrawal by Subject	0	3	5	4
Randomized Phase 2 Adverse Event	0	0	0	1
Randomized Phase 2 Comorbidities	0	2	2	2
Randomized Phase 2 Rising PSA, not as defined by protocol	0	2	5	2
Randomized Phase 2 Disenrolled before treatment	0	1	1	2
Randomized Phase 2 Patient stopped taking study drug	0	0	0	1
Randomized Phase 2 Patient transferred to other facility	0	0	1	0

Baseline Characteristics

Baseline characteristics were not collected for subjects who withdrew from the study. ECOG was not analyzed in the dose-escalation phase.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose-escalation Phase:Muscadine Plus Grape Skin Extract (MPX) n=14 Participants Muscadine Plus Grape Skin Extract: Phase I Dose-escalation starts at 500mg daily for 1 cycle (28 days), then increased to 1000mg for 2nd cycle, then increased to 2000mg daily for 3rd cycle, then increased to 3000mg daily for 4th cycle, then increased to maximum dose of 4000mg daily for final cycle. Pills given by mouth once daily for 28 days per cycle.	Phase 2: Placebo Control n=24 Participants Randomly-assigned participants receive 8 capsules once daily of placebo composed of pulverized rice for up to 12 cycles (28 days per cycle).	Phase 2: Low-dose MPX n=56 Participants Randomly-assigned participants receive one capsule of drug (500mg MPX) and seven capsules of placebo composed of pulverized rice, once daily for up to 12 cycles (28 days per cycle).	Phase 2: High-dose MPX n=49 Participants Randomly-assigned participants receive 8 capsules of drug (4000mg MPX) once daily for up to 12 cycles (28 days per cycle).	Total n=143 Participants Total of all reporting groups
Age, Continuous	62.6 years STANDARD_DEVIATION 7.5 • n=14 Participants	69 years STANDARD_DEVIATION 7.1 • n=24 Participants	67 years STANDARD_DEVIATION 7.2 • n=56 Participants	68 years STANDARD_DEVIATION 6.9 • n=49 Participants	67.2 years STANDARD_DEVIATION 7.1 • n=143 Participants
Sex: Female, Male Female	0 Participants n=14 Participants	0 Participants n=24 Participants	0 Participants n=56 Participants	0 Participants n=49 Participants	0 Participants n=143 Participants
Sex: Female, Male Male	14 Participants n=14 Participants	24 Participants n=24 Participants	56 Participants n=56 Participants	49 Participants n=49 Participants	143 Participants n=143 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=14 Participants	0 Participants n=24 Participants	0 Participants n=56 Participants	0 Participants n=49 Participants	0 Participants n=143 Participants
Race (NIH/OMB) Asian	0 Participants n=14 Participants	0 Participants n=24 Participants	0 Participants n=56 Participants	0 Participants n=49 Participants	0 Participants n=143 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=14 Participants	0 Participants n=24 Participants	0 Participants n=56 Participants	0 Participants n=49 Participants	0 Participants n=143 Participants
Race (NIH/OMB) Black or African American	4 Participants n=14 Participants	6 Participants n=24 Participants	12 Participants n=56 Participants	10 Participants n=49 Participants	32 Participants n=143 Participants
Race (NIH/OMB) White	10 Participants n=14 Participants	18 Participants n=24 Participants	43 Participants n=56 Participants	38 Participants n=49 Participants	109 Participants n=143 Participants
Race (NIH/OMB) More than one race	0 Participants n=14 Participants	0 Participants n=24 Participants	0 Participants n=56 Participants	0 Participants n=49 Participants	0 Participants n=143 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=14 Participants	0 Participants n=24 Participants	1 Participants n=56 Participants	1 Participants n=49 Participants	2 Participants n=143 Participants
Region of Enrollment United States	14 participants n=14 Participants	24 participants n=24 Participants	56 participants n=56 Participants	49 participants n=49 Participants	143 participants n=143 Participants
Eastern Cooperative Oncology Group (ECOG) 0	—	18 Participants n=23 Participants • Baseline characteristics were not collected for subjects who withdrew from the study. ECOG was not analyzed in the dose-escalation phase.	52 Participants n=54 Participants • Baseline characteristics were not collected for subjects who withdrew from the study. ECOG was not analyzed in the dose-escalation phase.	39 Participants n=47 Participants • Baseline characteristics were not collected for subjects who withdrew from the study. ECOG was not analyzed in the dose-escalation phase.	109 Participants n=124 Participants • Baseline characteristics were not collected for subjects who withdrew from the study. ECOG was not analyzed in the dose-escalation phase.
Eastern Cooperative Oncology Group (ECOG) 1	—	5 Participants n=23 Participants • Baseline characteristics were not collected for subjects who withdrew from the study. ECOG was not analyzed in the dose-escalation phase.	2 Participants n=54 Participants • Baseline characteristics were not collected for subjects who withdrew from the study. ECOG was not analyzed in the dose-escalation phase.	8 Participants n=47 Participants • Baseline characteristics were not collected for subjects who withdrew from the study. ECOG was not analyzed in the dose-escalation phase.	15 Participants n=124 Participants • Baseline characteristics were not collected for subjects who withdrew from the study. ECOG was not analyzed in the dose-escalation phase.
Gleason score ≤6, 3+4	—	11 Participants n=24 Participants • Gleason score was recorded differently in the dose-escalation phase and phase 2.	25 Participants n=56 Participants • Gleason score was recorded differently in the dose-escalation phase and phase 2.	23 Participants n=49 Participants • Gleason score was recorded differently in the dose-escalation phase and phase 2.	59 Participants n=129 Participants • Gleason score was recorded differently in the dose-escalation phase and phase 2.
Gleason score ≥8, 4+3	—	13 Participants n=24 Participants • Gleason score was recorded differently in the dose-escalation phase and phase 2.	31 Participants n=56 Participants • Gleason score was recorded differently in the dose-escalation phase and phase 2.	26 Participants n=49 Participants • Gleason score was recorded differently in the dose-escalation phase and phase 2.	70 Participants n=129 Participants • Gleason score was recorded differently in the dose-escalation phase and phase 2.
Gleason score 6	3 Participants n=14 Participants • Gleason score was recorded differently in the dose-escalation phase and phase 2.	—	—	—	3 Participants n=14 Participants • Gleason score was recorded differently in the dose-escalation phase and phase 2.
Gleason score 7	7 Participants n=14 Participants • Gleason score was recorded differently in the dose-escalation phase and phase 2.	—	—	—	7 Participants n=14 Participants • Gleason score was recorded differently in the dose-escalation phase and phase 2.
Gleason score 8	1 Participants n=14 Participants • Gleason score was recorded differently in the dose-escalation phase and phase 2.	—	—	—	1 Participants n=14 Participants • Gleason score was recorded differently in the dose-escalation phase and phase 2.
Gleason score 9	3 Participants n=14 Participants • Gleason score was recorded differently in the dose-escalation phase and phase 2.	—	—	—	3 Participants n=14 Participants • Gleason score was recorded differently in the dose-escalation phase and phase 2.
Baseline PSA doubling time (PSADT)	13 months STANDARD_DEVIATION 10.1 • n=14 Participants • Baseline PSADT was recorded as a mean in the dose-escalation phase, versus as number of participants with greater than or less than 9 months PSADT in Phase 2.	—	—	—	13 months STANDARD_DEVIATION 10.1 • n=14 Participants • Baseline PSADT was recorded as a mean in the dose-escalation phase, versus as number of participants with greater than or less than 9 months PSADT in Phase 2.
Baseline PSADT ≤9 months	—	13 Participants n=23 Participants • Baseline PSADT was recorded as a mean in the dose-escalation phase, versus as number of participants with greater than or less than 9 months PSADT in Phase 2.	32 Participants n=55 Participants • Baseline PSADT was recorded as a mean in the dose-escalation phase, versus as number of participants with greater than or less than 9 months PSADT in Phase 2.	27 Participants n=48 Participants • Baseline PSADT was recorded as a mean in the dose-escalation phase, versus as number of participants with greater than or less than 9 months PSADT in Phase 2.	72 Participants n=126 Participants • Baseline PSADT was recorded as a mean in the dose-escalation phase, versus as number of participants with greater than or less than 9 months PSADT in Phase 2.
Baseline PSADT >9 months	—	10 Participants n=23 Participants • Baseline PSADT was recorded as a mean in the dose-escalation phase, versus as number of participants with greater than or less than 9 months PSADT in Phase 2.	23 Participants n=55 Participants • Baseline PSADT was recorded as a mean in the dose-escalation phase, versus as number of participants with greater than or less than 9 months PSADT in Phase 2.	21 Participants n=48 Participants • Baseline PSADT was recorded as a mean in the dose-escalation phase, versus as number of participants with greater than or less than 9 months PSADT in Phase 2.	54 Participants n=126 Participants • Baseline PSADT was recorded as a mean in the dose-escalation phase, versus as number of participants with greater than or less than 9 months PSADT in Phase 2.
Prior therapy Radiation	4 Participants n=14 Participants • Participants in Phase 2 were not categorized as 'Radiation \& Surgery'. Only individual counts for each prior therapy received was recorded.	21 Participants n=24 Participants • Participants in Phase 2 were not categorized as 'Radiation \& Surgery'. Only individual counts for each prior therapy received was recorded.	49 Participants n=56 Participants • Participants in Phase 2 were not categorized as 'Radiation \& Surgery'. Only individual counts for each prior therapy received was recorded.	42 Participants n=49 Participants • Participants in Phase 2 were not categorized as 'Radiation \& Surgery'. Only individual counts for each prior therapy received was recorded.	116 Participants n=143 Participants • Participants in Phase 2 were not categorized as 'Radiation \& Surgery'. Only individual counts for each prior therapy received was recorded.
Prior therapy Surgery	1 Participants n=14 Participants • Participants in Phase 2 were not categorized as 'Radiation \& Surgery'. Only individual counts for each prior therapy received was recorded.	16 Participants n=24 Participants • Participants in Phase 2 were not categorized as 'Radiation \& Surgery'. Only individual counts for each prior therapy received was recorded.	40 Participants n=56 Participants • Participants in Phase 2 were not categorized as 'Radiation \& Surgery'. Only individual counts for each prior therapy received was recorded.	32 Participants n=49 Participants • Participants in Phase 2 were not categorized as 'Radiation \& Surgery'. Only individual counts for each prior therapy received was recorded.	89 Participants n=143 Participants • Participants in Phase 2 were not categorized as 'Radiation \& Surgery'. Only individual counts for each prior therapy received was recorded.
Prior therapy Radiation & Surgery	9 Participants n=14 Participants • Participants in Phase 2 were not categorized as 'Radiation \& Surgery'. Only individual counts for each prior therapy received was recorded.	—	—	—	9 Participants n=14 Participants • Participants in Phase 2 were not categorized as 'Radiation \& Surgery'. Only individual counts for each prior therapy received was recorded.
Prior therapy Cryotherapy	—	0 Participants n=24 Participants • Participants in Phase 2 were not categorized as 'Radiation \& Surgery'. Only individual counts for each prior therapy received was recorded.	49 Participants n=56 Participants • Participants in Phase 2 were not categorized as 'Radiation \& Surgery'. Only individual counts for each prior therapy received was recorded.	1 Participants n=49 Participants • Participants in Phase 2 were not categorized as 'Radiation \& Surgery'. Only individual counts for each prior therapy received was recorded.	50 Participants n=129 Participants • Participants in Phase 2 were not categorized as 'Radiation \& Surgery'. Only individual counts for each prior therapy received was recorded.
Prior therapy Brachytherapy	—	3 Participants n=24 Participants • Participants in Phase 2 were not categorized as 'Radiation \& Surgery'. Only individual counts for each prior therapy received was recorded.	5 Participants n=56 Participants • Participants in Phase 2 were not categorized as 'Radiation \& Surgery'. Only individual counts for each prior therapy received was recorded.	3 Participants n=49 Participants • Participants in Phase 2 were not categorized as 'Radiation \& Surgery'. Only individual counts for each prior therapy received was recorded.	11 Participants n=129 Participants • Participants in Phase 2 were not categorized as 'Radiation \& Surgery'. Only individual counts for each prior therapy received was recorded.
Prior therapy Androgen Deprivation Therapy (ADT)	—	2 Participants n=24 Participants • Participants in Phase 2 were not categorized as 'Radiation \& Surgery'. Only individual counts for each prior therapy received was recorded.	25 Participants n=56 Participants • Participants in Phase 2 were not categorized as 'Radiation \& Surgery'. Only individual counts for each prior therapy received was recorded.	19 Participants n=49 Participants • Participants in Phase 2 were not categorized as 'Radiation \& Surgery'. Only individual counts for each prior therapy received was recorded.	46 Participants n=129 Participants • Participants in Phase 2 were not categorized as 'Radiation \& Surgery'. Only individual counts for each prior therapy received was recorded.
Superoxide dismutase 2 (SOD2) genotype Alanine/Alanine (Ala/Ala)	—	5 Participants n=21 Participants • SOD2 genotype was not recorded in dose-escalation phase. In Phase 2, SOD2 genotype was not recorded for all participants if data was unavailable.	12 Participants n=44 Participants • SOD2 genotype was not recorded in dose-escalation phase. In Phase 2, SOD2 genotype was not recorded for all participants if data was unavailable.	10 Participants n=37 Participants • SOD2 genotype was not recorded in dose-escalation phase. In Phase 2, SOD2 genotype was not recorded for all participants if data was unavailable.	27 Participants n=102 Participants • SOD2 genotype was not recorded in dose-escalation phase. In Phase 2, SOD2 genotype was not recorded for all participants if data was unavailable.
Superoxide dismutase 2 (SOD2) genotype Alanine/Valine (Ala/Val)	—	11 Participants n=24 Participants • SOD2 genotype was not recorded in dose-escalation phase. In Phase 2, SOD2 genotype was not recorded for all participants if data was unavailable.	21 Participants n=56 Participants • SOD2 genotype was not recorded in dose-escalation phase. In Phase 2, SOD2 genotype was not recorded for all participants if data was unavailable.	22 Participants n=49 Participants • SOD2 genotype was not recorded in dose-escalation phase. In Phase 2, SOD2 genotype was not recorded for all participants if data was unavailable.	54 Participants n=129 Participants • SOD2 genotype was not recorded in dose-escalation phase. In Phase 2, SOD2 genotype was not recorded for all participants if data was unavailable.
Superoxide dismutase 2 (SOD2) genotype Valine/Valine (Val/Val)	—	5 Participants n=24 Participants • SOD2 genotype was not recorded in dose-escalation phase. In Phase 2, SOD2 genotype was not recorded for all participants if data was unavailable.	11 Participants n=56 Participants • SOD2 genotype was not recorded in dose-escalation phase. In Phase 2, SOD2 genotype was not recorded for all participants if data was unavailable.	5 Participants n=49 Participants • SOD2 genotype was not recorded in dose-escalation phase. In Phase 2, SOD2 genotype was not recorded for all participants if data was unavailable.	21 Participants n=129 Participants • SOD2 genotype was not recorded in dose-escalation phase. In Phase 2, SOD2 genotype was not recorded for all participants if data was unavailable.

PRIMARY outcome

Timeframe: Up to 7 months post-intervention

To determine the recommended dosing for Muscadine Plus and to evaluate the safety and tolerability of Muscadine Plus in prostate cancer patients with rising PSA following definitive therapy.

Outcome measures

Outcome measures
Measure	Dose-escalation Phase:Muscadine Plus Grape Skin Extract (MPX) n=14 Participants Muscadine Plus Grape Skin Extract: Phase I Dose-escalation starts at 500mg daily for 1 cycle (28 days), then increased to 1000mg for 2nd cycle, then increased to 2000mg daily for 3rd cycle, then increased to 3000mg daily for 4th cycle, then increased to maximum dose of 4000mg daily for final cycle. Pills given by mouth once daily for 28 days per cycle.	Phase 2: Placebo Control Randomly-assigned participants receive 8 capsules once daily of placebo composed of pulverized rice for up to 12 cycles (28 days per cycle).	Phase 2: Low-dose MPX Randomly-assigned participants receive one capsule of drug (500mg MPX) and seven capsules of placebo composed of pulverized rice, once daily for up to 12 cycles (28 days per cycle).	Phase 2: High-dose MPX Randomly-assigned participants receive 8 capsules of drug (4000mg MPX) once daily for up to 12 cycles (28 days per cycle).
(Phase I) Maximum Tolerated Dose	4000 mg	—	—	—

PRIMARY outcome

Timeframe: Change from baseline to month 12

To define the effects of placebo and two different daily doses of MPX on PSADT in men who have rising PSA after initial definitive therapy for localized prostate cancer.

Outcome measures

Outcome measures
Measure	Dose-escalation Phase:Muscadine Plus Grape Skin Extract (MPX) n=20 Participants Muscadine Plus Grape Skin Extract: Phase I Dose-escalation starts at 500mg daily for 1 cycle (28 days), then increased to 1000mg for 2nd cycle, then increased to 2000mg daily for 3rd cycle, then increased to 3000mg daily for 4th cycle, then increased to maximum dose of 4000mg daily for final cycle. Pills given by mouth once daily for 28 days per cycle.	Phase 2: Placebo Control n=52 Participants Randomly-assigned participants receive 8 capsules once daily of placebo composed of pulverized rice for up to 12 cycles (28 days per cycle).	Phase 2: Low-dose MPX n=40 Participants Randomly-assigned participants receive one capsule of drug (500mg MPX) and seven capsules of placebo composed of pulverized rice, once daily for up to 12 cycles (28 days per cycle).	Phase 2: High-dose MPX Randomly-assigned participants receive 8 capsules of drug (4000mg MPX) once daily for up to 12 cycles (28 days per cycle).
(Phase II) Prostate Specific Antigen Doubling Time (PSADT)	0.9 months Interval -6.7 to 83.1	1.5 months Interval -10.3 to 87.2	0.9 months Interval -27.3 to 88.1	—

SECONDARY outcome

Timeframe: At month 12 post-intervention

Adverse events reported verbally by patient and documented in study notes.

Outcome measures

Outcome measures
Measure	Dose-escalation Phase:Muscadine Plus Grape Skin Extract (MPX) n=14 Participants Muscadine Plus Grape Skin Extract: Phase I Dose-escalation starts at 500mg daily for 1 cycle (28 days), then increased to 1000mg for 2nd cycle, then increased to 2000mg daily for 3rd cycle, then increased to 3000mg daily for 4th cycle, then increased to maximum dose of 4000mg daily for final cycle. Pills given by mouth once daily for 28 days per cycle.	Phase 2: Placebo Control n=23 Participants Randomly-assigned participants receive 8 capsules once daily of placebo composed of pulverized rice for up to 12 cycles (28 days per cycle).	Phase 2: Low-dose MPX n=55 Participants Randomly-assigned participants receive one capsule of drug (500mg MPX) and seven capsules of placebo composed of pulverized rice, once daily for up to 12 cycles (28 days per cycle).	Phase 2: High-dose MPX n=47 Participants Randomly-assigned participants receive 8 capsules of drug (4000mg MPX) once daily for up to 12 cycles (28 days per cycle).
Number of Participants With Adverse Events as a Measure of Safety and Tolerability	7 Participants	19 Participants	38 Participants	32 Participants

SECONDARY outcome

Timeframe: At month 12 post-intervention

Population: Data was not collected for this secondary outcome measure.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At month 12 post-intervention

Population: Patients counted in the analysis were evaluable if they completed at least six cycles of treatment prior to discontinuation

Change in PSA values drawn over study period, taken every 3 months. PSA is measured in ng/mL