Trial of Quercetin, Bromelain, Rye Flower Pollen & Papain on Reducing Severity of Radiation-Induced Prostatitis

Phase 2

Terminated

Conditions: Prostate Adenocarcinoma

Interventions: Drug: Q-Urol
Drug: Placebo

Registration Number: NCT04252625

Lead Sponsor: University of Utah

Brief Summary: This study will assess the difference in prostatitis symptoms in men with localized prostate cancer following brachytherapy taking Q-Urol relative to placebo.

Detailed Description: This is a Phase 2, double-blinded, placebo-controlled trial assessing the safety of Q-Urol use after brachytherapy placement in patients with localized prostate cancer. Patients will be randomized in a 1:1 ratio to receive Q-Urol/Placebo twice daily for 6 weeks after brachytherapy placement. Questionnaires will be administered pre- and post-treatment to assess the change in prostatitis symptoms and quality of life measures. The mean values between groups will be compared.

Recruitment & Eligibility

Status: TERMINATED

Sex: Male

Target Recruitment: 10

Inclusion Criteria

Male subjects aged ≥ 18 years.
Men with histologically proven localized prostate adenocarcinoma, stage I - III (as defined by American Joint Committee on Cancer (AJCC) 8th edition), who have selected treatment with brachytherapy with or without external beam radiation, with or without androgen deprivation therapy.
Fluent in speaking and reading English.
Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
Adequate organ function as defined as:
- Hepatic:
  - Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN)
  - aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 × institutional ULN
- Renal:
  - Estimated creatinine clearance ≥ 30 mL/min by Cockcroft-Gault formula:
    - Males: ((140-age)×weight[kg])/(serum creatinine [mg/dL]×72)
Highly effective contraception for both male and their female partners of childbearing potential throughout the study and for at least 5 days after last study treatment administration if the risk of conception exists.
Median life expectancy ≥ 5 years as calculated by the Lee and Schonberg Index (https://eprognosis.ucsf.edu/leeschonberg.php)
Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

Exclusion Criteria

Baseline AUA symptom scores > 15.
Prior diagnosis of chronic prostatitis type II through IV.
Subject has received systemic therapy intended for the treatment of prostatitis (including herbal supplements) ≤ 14 days of starting study treatment.
Subject has received a fluoroquinolone antibiotic (e.g. ciprofloxacin, norfloxacin, ofloxacin levofloxacin, etc.) ≤ 3 days of starting study treatment.
Subject is actively on anti-inflammatory medications for other medical conditions, unless approved by PI.
Subject has undergone transurethral resection of the prostate (TURP).
Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
History of irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia, and interstitial cystitis-bladder pain syndrome (IC/BPS).
History of symptomatic hypotension, falls, or syncope
History of hypoglycemia.
Actively abusing alcohol or drugs
Subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
- Congestive heart failure
- Diabetes
- Pulmonary artery hypertension
- Any clinically significant condition that requires therapy with diuretic medications for any indication other than the management of hypertension.
- Other clinically significant disorders that would, in the opinion of the treating investigator, preclude safe study participation.
Known prior severe hypersensitivity to investigational product or any component in its formulations (NCI CTCAE v5.0 Grade ≥ 3).
Known allergy to pineapple or pineapple containing products.
Subjects taking prohibited medications as described in Section 7.3 A washout period of prohibited medications for a period of at least 5 half-lives or as clinically indicated should occur prior to the start of treatment.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1: Q-Urol	Q-Urol	Patients will be randomized in a 1:1 ratio to receive Q-Urol, two capsules, twice daily for 6 weeks after brachytherapy placement. Questionnaires will be administered pre- and post-treatment to assess the change in prostatitis symptoms and quality of life measures. The mean values between groups will be compared.
Arm 2: Placebo	Placebo	Patients will be randomized in a 1:1 ratio to receive Placebo, two capsules, twice daily for 6 weeks after brachytherapy placement. Questionnaires will be administered pre- and post-treatment to assess the change in prostatitis symptoms and quality of life measures. The mean values between groups will be compared.

Primary Outcome Measures

Name	Time	Method
National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI)	up to 6 weeks after the start of study treatment	This outcome will report the mean score of the NIH-CPSI, a 13-item questionnaire. This questionnaire will report 4 sub-scores, Pain, Urinary Symptoms, Quality of Life (QOL) Impact, and Pain + Urinary score, and the total score. Pain: The sum of 6 items (0 No-1 Yes), one scale (0 Never-5 Always), and one scale (0 No Pain-10 Pain as bad as you can imagine); Range: 0-21, higher values indicating worse outcomes. Urinary Symptoms: The sum of 2 urine items (0 Not at all-5 Almost always); Range: 0-10, higher values indicating worse outcomes. QOL Impact: The sum of 2 items (0 None-3 A lot) and 1 scale (0 Delighted-6 Terrible); Range: 0-12, higher values indicating worse outcomes. Pain and Urinary sub-score: The sum of the Pan and Urinary Symptoms scores; Range: 0-31, higher values indicating worse outcomes. Total Score: The sum of all questions; Range: 0-43, higher values indicating worse outcomes. This outcome measure is assessed at 6 weeks after the start of study treatment.

Secondary Outcome Measures

Name	Time	Method
The Expanded Prostate Cancer Index Composite (EPIC) Assessment	up to 6 weeks after the start of study treatment	Health Related Quality of Life (HRQOL) will be assessed with EPIC questionnaires. Items are standardized to a 0-100 scale and are averaged to calculate four subscale scores (Urinary Summary, Bowel Summary, Sexual Summary, Hormonal Summary). A higher score (max 100) represents better HRQOL, and a lower score (min 0) represents worse HRQOL.
The International Prostate Symptom Score (I-PSS) Assessment	up to 6 weeks after the start of study treatment	Health Related Quality of Life (HRQOL) will be assessed with International Prostate Symptom Score (I-PSS). This is a questionnaire with 7 questions concerning urinary symptoms (from 0 to 5). A high score (max 35) indicates worse HRQOL and a low score (min 0) represents a better HRQOL. These score are reported as Mild (0-7), moderate (8-19) or Severe (20-35). total score ranges from 0 to 35 (asymptomatic to very symptomatic).
The Rectal Function Assessment Score (R-FAS) Assessment	At the End of Treatment Visit, up to 8 weeks after initiation of study treatment.	Health Related Quality of Life (HRQOL) will be assessed with the R-FAS 10-item questionnaires. Question 10 does not count toward the total score. 9 questions are scored from 0-3. A higher score represents poorer bowel function (max 27) and a lower score represents better bowel function (min 0).
Sexual Health Inventory for Men (SHIM) Assessment	At the End of Treatment Visit, up to 8 weeks after initiation of study treatment.	The SHIM is a 5 point questionnaire with ratings from 0-5 to assess Health Related Quality of Life (HRQOL). The sum of the SHIM score is categorized to Severe Erectile Dysfunction ED (0-7), Moderate ED (8-11), Mild to Moderate ED (12-16), Mild ED (17-21), No signs of ED (22-25). This outcome will report the count of participants in each category.
Impact on Serum Biomarkers of Inflammation - Erythrocyte Sedimentation Rate (ESR)	At the End of Treatment Visit, up to 8 weeks after initiation of study treatment.	The inflammation marker, erythrocyte sedimentation rate (ESR), was collected at the End of Treatment visit for comparison between treatment and placebo groups. This outcome will report the mean ESR of each arm.
Impact on Serum Biomarkers of Inflammation - C-reactive Protein	At the End of Treatment Visit, up to 8 weeks after initiation of study treatment.	The inflammation marker, C-reactive protein, was collected at the End of Treatment visit for comparison between treatment and placebo groups. This outcome will report the mean C-reactive protein of each arm.
Impact on Serum Biomarkers of Inflammation - Prostate-specific Antigen (PSA)	At the End of Treatment Visit, up to 8 weeks after initiation of study treatment.	The inflammation marker, Prostate-specific antigen (PSA), was collected at the End of Treatment visit for comparison between treatment and placebo arm. This outcome will report the mean PSA of each arm.
Adverse Events by Grade	up to 10.5 weeks after initiation of study treatment	To assess safety of Q-Urol compared to placebo. The severity of adverse events was assessed using CTCAE v5.0 criteria, a 1-5 scale with higher numbers indicating greater severity. Grade 1 indicates "mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated" and Grade 5 indicates "death related to AE". This outcome measure will report the following: The count of participants who had a grade 1-2 event, related to study treatment. The count of the participants who had a grade 3-4 event, related to study treatment. The count of the participants who had a grade 5 event or higher. Subjects were monitored for adverse events from the start of treatment until 30 days after the last dose of study treatment.
Days of Pain Medication	up to 28 days after initiation of study treatment	To assess effect on prostatitis-related pain in men with localized prostate cancer following brachytherapy taking Q-Urol relative to placebo. This outcome will report the mean number of days participants took pain medication as documented on a self reported Pain Management Diary. This was followed for 28 days; the minimum number of days is 0 and the maximum number is 28.

Trial Locations

Locations (2): Huntsman Cancer Institute at University of Utah
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Salt Lake City, Utah, United States
Huntsman Cancer Institute
🇺🇸
Salt Lake City, Utah, United States
Huntsman Cancer Institute at University of Utah
🇺🇸Salt Lake City, Utah, United States