Clinical trial NCT05629494: Anti-inflammatory Drugs and Serum Prostate-Specific Antigen Test
Official title: Effect of Non-steroidal Anti-inflammatory Drugs on Serum Prostate Specific Antigen Level
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Prostate Cancer
Prostate Inflammation
PSA
Keywords: Prostate-specific antigen
PSA test
Prostate biopsy
non-steroidal anti-inflammatory drugs NSAIDS
Lead sponsor: Albany Medical College
Sponsor class: OTHER
First posted: 2022-11-29
Enrollment: 198
Sex: MALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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:

1. Repeat PSA test after several weeks or
2. 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.

Eligibility criteria: Inclusion Criteria:

* Male patients age between 18-80 years old with a screening PSA \> 3 ng/ml being considered for additional diagnostic testing (e.g., MRI, biopsy)
* Normal digital rectal examination within the past two years. A documented normal digital rectal examination by another physician or advanced practice provider (NP, PA, etc) is acceptable.
* No clinical symptoms concerning for acute urinary tract infection (e.g. dysuria, malodorous urine, positive urine culture)

Exclusion Criteria:

* History of hypersensitivity or allergy to ibuprofen or NSAIDs.
* History of peptic ulcer disease, GI bleeding or NSAIDs induced GI adverse events
* Known bleeding disorders
* Known severe chronic kidney disease: eGFR \< 30 mL/min/1.73 m2
* Heart failure, significant heart disease
* Poorly controlled hypertension
* Active urinary tract infections or bacteriuria
* Concomitant use of 5-alpha reductase inhibitors (finasteride, dutasteride) unless patient has been taking it for at least 6 months
* Known prostate cancer or underwent prostate MRI or biopsy in the last year
* Urinary tract instrumentation in the past 6 weeks (catheter, cystoscopy)
* Concomitant anti-inflammatory or steroidal drugs
* Concomitant dual-antiplatelet or anticoagulant therapy use except aspirin 81 mg alone
* Know history of severe liver disease determined by abnormal liver function tests (elevated AST or ALT \> 3X ULN based on exiting history or labs)
* Any other medical contraindication to NSAIDs

Primary outcomes:
measure: Difference in the extent of changes in PSA level between the study groups
timeFrame: 6 weeks
measure: Participants with change in PSA level to below the age-specific PSA threshold
timeFrame: 6 weeks
Secondary outcomes:
measure: Determine the incidence of acute kidney injury following a short course of ibuprofen
timeFrame: 1 year
measure: Durability of the change in PSA levels
timeFrame: 1 to 1.5 year
measure: Changes in voiding symptoms as measured by the International Prostate Symptom Score
timeFrame: 3-12 months
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Hershey
country: United States
facility: Penn State-Hershey Medical Center
state: Pennsylvania
Study officials:
affiliation: Albany Medical College
name: Badar Mian, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Penn State Health
name: Jay Raman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Chicago
name: Scott Eggener, MD
role: PRINCIPAL_INVESTIGATOR
References: