Anti-inflammatory Drugs and Serum Prostate-Specific Antigen Test (ADAPT-PSA)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer; PSA; Prostate Inflammation
• Intervention / Treatment: Diagnostic test: PSA test; Drug: Ibuprofen 400 mg, TID

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.

• Study Type: Interventional
• Enrollment (Estimated): 198
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Brenda Romeo; Phone Number: 518-262-8579; Email: amcurologyresearch@amc.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago Medical Center
      • Contact: Scott Eggener, MD; Phone Number: 773-702-1860; Email: seggener@bsd.uchicago.edu
  • New York
    • Albany, New York, United States, 12208
      • Recruiting
      • Albany Medical Center
      • Contact: Badar M. Mian, MD; Phone Number: 518-262-7558; Email: mianb@amc.edu
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Recruiting
      • Penn State-Hershey Medical Center
      • Contact: Jay Raman, MD; Phone Number: 717-531-8887; Email: jraman@pennstatehealth.psu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Repeat serum PSA test; Repeat PSA test at 6 (± 1) weeks, without any treatment	Diagnostic test: PSA test; PSA test will be repeated in 6 weeks
Experimental: Treatment with NSAIDS; Treatment with Ibuprofen 400 mg, 3 times per day, then repeat PSA test at 6 (± 1) weeks	Diagnostic test: PSA test; PSA test will be repeated in 6 weeks; Drug: Ibuprofen 400 mg, TID; Participants will receive Ibuprofen 400 mg 3 times per day for 10 days.; Other Names: Motrin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Difference in the extent of changes in PSA level between the study groups	Difference in PSA levels, within and between groups	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Determine the incidence of acute kidney injury following a short course of ibuprofen	To determine if the treatment and PSA changes correlates with change in urinary symptoms	1 year

Collaborators and Investigators

• Sponsor: Albany Medical College
• Investigators: Principal Investigator: Scott Eggener, MD, University of Chicago; Principal Investigator: Badar Mian, MD, Albany Medical College; Principal Investigator: Jay Raman, MD, Penn State Health

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2022
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: September 3, 2022
• First Submitted That Met QC Criteria: November 16, 2022
• First Posted (Actual): November 29, 2022

Study Record Updates

• Last Update Posted (Actual): October 18, 2024
• Last Update Submitted That Met QC Criteria: October 17, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Prostate-specific antigen; Prostate biopsy; PSA test; non-steroidal anti-inflammatory drugs NSAIDS
• Additional Relevant MeSH Terms: Pathologic Processes; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Inflammation; Prostatitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ibuprofen
• Other Study ID Numbers: 6587

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No