Anti-inflammatory Drugs and Serum Prostate-Specific Antigen Test

Study Overview
=================
Brief Summary
-----------------
Prostate cancer is the most frequently diagnosed cancer in men in the Unites States. Nearly 1 million prostate biopsy procedures are performed in the United States annually and elevated prostate-specific antigen (PSA) level is the primary reason for prostate biopsy in > 90% of cases. However, at the PSA levels which trigger prostate biopsy, often no cancer is found in prostate biopsy specimens. PSA test can be elevated due to reasons other than cancer such as inflammation or natural variation in the level. Investigators plan to treat men with elevated PSA level with over the counter anti-inflammatory medications (ibuprofen, naproxen) to see if the PSA level will decrease to an acceptable level.

Detailed Description
-----------------
It's known that PSA level can be elevated due to reasons other than prostate cancer including benign prostatic hypertrophy, prostatitis or other urinary tract infections, non-infectious inflammation, and physiologic variation over time. Consequently, nearly 50% of prostate biopsy procedures performed due to elevated PSA level do not yield any cancer , but still expose the patients to the risks of the procedure related complications (discomfort/pain, anxiety, bleeding, infection, and cost). Thus, measures to improve the reliability of PSA test, and potentially avoiding unnecessary procedures, are of significant importance to the patient and healthcare system. It is common practice to check PSA level annually. PSA test results can vary over time, either due to the imprecision in the analysis and/or due to the biologic variability. This can result in an apparent rise in PSA level when no clinically meaningful rise had occurred. Its estimated that the average lab variation in PSA was approximately 6% and the average biologic variation about 14%. This, it is recommended that isolated elevation in PSA level should be confirmed after several weeks, and before proceeding with further interventions, including prostate biopsy. Sub-clinical, histologic Inflammation (presence of inflammatory cells) within the prostate tissue and its effect on PSA level has been reported in various settings. In two population-based studies, men who were regularly using over the counter (OTC) nonsteroidal anti-inflammatory drugs (NSAIDs, e.g ibuprofen, naproxen) had lower PSA levels compared to non-users. Currently, two strategies are utilized in clinical practice to ensure that the PSA level is truly elevated: Repeat PSA test after several weeks or A short course of OTC NSAIDs, and then repeat PSA test Investigators propose to conduct a randomized study to determine the effect of NSAIDs on PSA level compared to the biologic variations in PSA level noted upon repeat testing.

Official Title
-----------------
Effect of Non-steroidal Anti-inflammatory Drugs on Serum Prostate Specific Antigen Level

Conditions
-----------------
PSA, Prostate Cancer, Prostate Inflammation

Intervention / Treatment
-----------------
* Drug: Ibuprofen or Naproxen
* Diagnostic Test: PSA test


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All men with an elevated PSA level (as designated by their medical provider) will be invited to participate in the study Exclusion Criteria: Inability to use NSAIDs (allergy, side effects) History of peptic ulcer disease or GI bleeding Any bleeding disorders Chronic kidney disease: eGlomerular Filtration Rate < 45 Heart failure, significant heart disease Poorly controlled hypertension Signs or symptoms of urinary tract infections Use of 5-alpha reductase inhibitors (finasteride, dutasteride) within past 6 months History of prostate cancer Urinary tract instrumentation in the past 2 months (catheter, endoscopy) Regular NSAIDs use (> once per week) Daily Aspirin use (325 mg or 81 mg), UNLESS it can be held for the study period Other anti-platelet or anticoagulant therapy Steroids use (except occasionally inhaled formulations) Liver disease, abnormal liver function tests

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Repeat serum PSA test<br>Repeat PSA test at 6 (± 1) weeks, without any treatment | Diagnostic Test: PSA test<br>* PSA test will repeated in 6 weeks<br>|
| Experimental: Treatment with NSAIDS<br>Treatment with NSAIDS (Ibuprofen 400 mg, 3 times per day or Naproxen 220 mg, twice per day for 10 days), then repeat PSA test at 6 (± 1) weeks | Drug: Ibuprofen or Naproxen<br>* Participants will receive either Ibuprofen 400 mg 3 times per day or Naproxen 220 mg, twice per day for 10 days.<br>* Other names: Motrin, Naprosyn;Diagnostic Test: PSA test<br>* PSA test will repeated in 6 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in the extent of changes in PSA level between the study groups | Difference in PSA, within and between groups | 6 weeks | 
| Participants with change in PSA level to below the age-specific PSA threshold | To determine if changes in PSA level were sufficient to avoid intervention | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between the magnitude of change in PSA level and biopsy results | To determine if the PSA changes correlate with the cancer diagnosis | 1 year | 
| Durability of the change in PSA levels | Serial PSA levels will be examined to determine whether the change in PSA level is transient or durable | 1 to 1.5 year | 
| Changes in voiding symptoms as measured by the International Prostate Symptom Score | Patient reported symptom score, ranging from 0-35 (higher score=worse outcome) | 3-12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PSA test, Prostate-specific antigen, Prostate biopsy, non-steroidal anti-inflammatory drugs NSAIDS