Anti-inflammatory Drugs for Elevated Prostate-Specific Antigen Levels

(ADAPT-PSA Trial)

Recruiting at 2 trial locations

Overseen By Brenda Romeo

Age: 18+

Sex: Male

Trial Phase: Phase 4

Sponsor: Albany Medical College

Must not be taking: 5-alpha reductase, Anti-inflammatory

Disqualifiers: Kidney disease, Heart disease, Hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 6 weeks

198 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop taking my current medications for the trial?

The trial requires you to stop taking certain medications. You cannot participate if you are using 5-alpha reductase inhibitors unless you've been on them for at least 6 months, or if you are taking anti-inflammatory or steroidal drugs, or dual-antiplatelet or anticoagulant therapy (except aspirin 81 mg alone).

What data supports the idea that Anti-inflammatory Drugs for Elevated Prostate-Specific Antigen Levels is an effective treatment?

The available research shows that nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen can help reduce inflammation and lower prostate-specific antigen (PSA) levels due to inflammation in the prostate. However, when compared to a treatment using pollen extract and vitamins (DEPROX 500®) for a related condition, chronic prostatitis/chronic pelvic pain syndrome, ibuprofen was less effective in improving symptoms and quality of life. This suggests that while NSAIDs may have some effect, they might not be the most effective option compared to other treatments for similar conditions. ^{1 2 3 4 5}

What safety data exists for ibuprofen and naproxen?

Ibuprofen and naproxen, both nonsteroidal anti-inflammatory drugs (NSAIDs), have been studied for their safety profiles. Ibuprofen is part of a fixed-dose combination with famotidine (Duexis) to reduce the risk of gastric and duodenal ulcers. Naproxen is available in combination with esomeprazole (Vimovo) to prevent NSAID-associated gastric ulcers. Studies show that naproxen/esomeprazole has a better upper gastrointestinal tolerability profile compared to naproxen alone and is similar to celecoxib. Both drugs have been shown to be effective in treating arthritic symptoms, with naproxen having a high therapeutic index and a shallow dose-response curve, indicating a low risk of significant drug interactions. However, there is a risk of gastrointestinal bleeding with both drugs, which is a consideration for long-term use. ^{6 7 8 9 10}

Is the drug Ibuprofen or Naproxen a promising treatment for high prostate-specific antigen levels?

Yes, Ibuprofen and Naproxen are promising drugs because they are effective anti-inflammatory agents. They help reduce inflammation and pain, which can be beneficial for conditions like elevated prostate-specific antigen levels. Both drugs are well-known for their ability to relieve symptoms in various inflammatory conditions. ^{6 7 11 12 13}

Research Team

Badar M. Mian, MD

Principal Investigator

Albany Medical College

Scott E. Eggener

Principal Investigator

University of Chicago

Jay Raman, MD

Principal Investigator

Penn State Health

Eligibility Criteria

Men with elevated PSA levels, which could indicate prostate issues, are eligible for this trial. They must not have bleeding disorders, severe kidney disease, recent urinary tract procedures, or be on certain medications like steroids and blood thinners. Men with a history of prostate cancer or current signs of urinary infection cannot join.

Inclusion Criteria

My doctor has told me my PSA levels are high.

Exclusion Criteria

I do not use steroids regularly, except for asthma or COPD.

I have a history of prostate cancer.

I have liver disease or abnormal liver tests.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a repeat PSA test or treatment with NSAIDs followed by a repeat PSA test

6 weeks

1 visit (in-person) for PSA test

Follow-up

Participants are monitored for changes in PSA levels and voiding symptoms

3-12 months

Long-term follow-up

Participants are monitored for durability of PSA level changes and incidence of acute kidney injury

1 to 1.5 years

Treatment Details

Interventions

• Ibuprofen or Naproxen

Trial Overview The study is testing if common anti-inflammatory drugs (Ibuprofen or Naproxen) can lower high PSA levels in men to avoid unnecessary biopsies. The effect of these over-the-counter medications on PSA will be monitored closely.

Participant Groups

Group I: Treatment with NSAIDS Experimental Treatment 2 Interventions

Treatment with Ibuprofen 400 mg, 3 times per day, then repeat PSA test at 6 (± 1) weeks

Group II: Repeat serum PSA test Active Control 1 Intervention

Repeat PSA test at 6 (± 1) weeks, without any treatment

Ibuprofen or Naproxen is already approved in United States, European Union for the following indications:

Approved in United States as Ibuprofen for:

• Pain relief
• Fever reduction
• Inflammation
• Menstrual cramps
• Osteoarthritis
• Rheumatoid arthritis

Approved in United States as Naproxen for:

• Pain relief
• Fever reduction
• Inflammation
• Osteoarthritis
• Rheumatoid arthritis
• Ankylosing spondylitis
• Tendinitis
• Bursitis
• Gout

Approved in European Union as Ibuprofen for:

• Pain relief
• Fever reduction
• Inflammation
• Menstrual cramps
• Osteoarthritis
• Rheumatoid arthritis

Approved in European Union as Naproxen for:

• Pain relief
• Fever reduction
• Inflammation
• Osteoarthritis
• Rheumatoid arthritis
• Ankylosing spondylitis
• Tendinitis
• Bursitis
• Gout

Who Is Running the Clinical Trial?

Albany Medical College

Lead Sponsor

Trials

96

Recruited

12,700+

Findings from Research

In a study of 78,165 men, NSAID users showed a lower detection rate of well-differentiated localized prostate tumors during PSA screening compared to nonusers, indicating that NSAID use may reduce overdiagnosis in this group.

The study found that PSA screening significantly decreased prostate cancer mortality among NSAID users (HR 0.66), while it did not show a similar benefit for nonusers (HR 0.95), suggesting that NSAIDs may enhance the effectiveness of screening in reducing mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Prostate-specific Antigen-based Prostate Cancer Screening Among Men Using Nonsteroidal Anti-inflammatory Drugs. Murtola, TJ., Vettenranta, AM., Talala, K., et al.[2021]

In a study of 12 patients with recurrent prostate cancer, treatment with the COX-2 inhibitor celecoxib led to significant reductions or stabilization of serum PSA levels in two-thirds of the participants after 3 months, indicating potential efficacy in managing biochemical relapse.

Celecoxib treatment resulted in a significant slowing of PSA doubling times, suggesting it may help delay disease progression without affecting testosterone levels, pointing to an androgen-independent mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of use of the cyclooxygenase-2 inhibitor celecoxib in recurrent prostate cancer after definitive radiation therapy or radical prostatectomy. Pruthi, RS., Derksen, JE., Moore, D.[2022]

In a Phase III trial involving 53 patients undergoing radiotherapy for prostate cancer, ibuprofen did not significantly relieve acute urinary or rectal symptoms compared to placebo, indicating it may not be effective for this purpose.

Despite the lack of symptom relief, the study suggests that nonsteroidal anti-inflammatory drugs like ibuprofen could have potential as radiation sensitizers, warranting further research into their mechanisms of action and optimal dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III study of ibuprofen versus placebo for radiation-induced genitourinary side effects. Coleman, CN., Kelly, L., Riese Daly, N., et al.[2019]

In a study of 87 males with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), the pollen extract DEPROX 500® significantly improved quality of life and reduced symptoms compared to ibuprofen, with 75.6% of patients reporting improvement versus 41.3% in the ibuprofen group.

DEPROX 500® was associated with fewer adverse events than ibuprofen, indicating it may be a safer alternative for treating CP/CPPS without severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pollen extract in association with vitamins provides early pain relief in patients affected by chronic prostatitis/chronic pelvic pain syndrome. Cai, T., Wagenlehner, FM., Luciani, LG., et al.[2021]

In a study of 40 patients with recurrent prostate cancer after radiation therapy or surgery, the COX-2 inhibitor celecoxib significantly slowed the rate of prostate-specific antigen (PSA) increase, with 90% of patients showing a positive response after 3 months.

The treatment did not affect testosterone levels, indicating that celecoxib may work through an androgen-independent mechanism, suggesting its potential to delay disease progression and extend the time before needing androgen deprivation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of celecoxib in prostate-specific antigen recurrent prostate cancer after definitive radiation therapy or radical prostatectomy. Pruthi, RS., Derksen, JE., Moore, D., et al.[2015]

Duexis, a combination of ibuprofen and famotidine, is FDA-approved for treating osteoarthritis and rheumatoid arthritis while also reducing the risk of NSAID-related gastric ulcers in at-risk patients.

Vimovo, which combines naproxen and esomeprazole, is also FDA-approved specifically for preventing gastric ulcers associated with NSAID use, highlighting the importance of protecting the stomach while managing pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A fixed-dose combination ibuprofen and famotidine (Duexis). [2013]

Naproxen sodium (Anaprox) is an effective anti-inflammatory and pain relief medication, primarily working by inhibiting prostaglandin synthesis, which is linked to relief from menstrual pain (dysmenorrhea).

The drug is rapidly absorbed in its sodium salt form, has a long half-life of about 13 hours, and is mostly excreted unchanged in urine, indicating a straightforward metabolism with a high therapeutic index and minimal significant drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naproxen sodium (Anaprox): pharmacology, pharmacokinetics and drug interactions. Segre, EJ.[2013]

In two 12-week studies, the naproxen/esomeprazole combination was found to be as effective as celecoxib in reducing pain and improving function in patients with knee osteoarthritis, indicating its efficacy as a treatment option.

The combination therapy also significantly reduced the incidence of gastric ulcers compared to enteric-coated naproxen alone, demonstrating a better gastrointestinal safety profile while being well tolerated by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naproxen/esomeprazole fixed-dose combination: for the treatment of arthritic symptoms and to reduce the risk of gastric ulcers. Dhillon, S.[2021]

In a study comparing 101,318 patients using naproxen sodium to 277,601 patients using ibuprofen, naproxen sodium was associated with a higher relative risk of upper gastrointestinal tract bleeding (UGIB), with an adjusted relative risk of 2.0.

Despite the increased relative risk, the overall incidence of UGIB was low for both medications, suggesting that while naproxen sodium poses a greater risk, the absolute risk remains small, particularly for patients with pre-existing conditions that elevate their risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal tract bleeding associated with naproxen sodium vs ibuprofen. Strom, BL., Schinnar, R., Bilker, WB., et al.[2013]

Naproxen/esomeprazole magnesium tablets are effective for treating symptoms of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis, showing equal efficacy compared to other NSAIDs like naproxen and celecoxib.

This combination therapy also offers better gastrointestinal safety, reducing the risk of dyspepsia and gastric ulcers compared to several other NSAIDs, making it a safer option for patients at risk of NSAID-associated gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of naproxen/esomeprazole magnesium tablets compared with non-specific NSAIDs and COX-2 inhibitors: a systematic review and network analyses. Datto, C., Hellmund, R., Siddiqui, MK.[2020]

Older pyrazole NSAIDs like phenylbutazone should be avoided in the elderly due to their high risk of pharmacokinetic interactions, while acidic NSAIDs can have their absorption affected by antacids, though the overall extent of absorption remains unchanged.

NSAIDs can significantly interact with other medications, especially those with narrow therapeutic windows, such as lithium and methotrexate, leading to potentially dangerous increases in blood concentrations, particularly in vulnerable populations like the elderly and those with renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic-pharmacodynamic drug interactions with nonsteroidal anti-inflammatory drugs. Brouwers, JR., de Smet, PA.[2018]

Fenoprofen, a new non-steroidal anti-inflammatory drug, has been shown to be as effective as moderate doses of aspirin for treating rheumatoid arthritis while generally causing fewer and milder side effects.

In comparisons with other similar medications, fenoprofen is comparable in effectiveness to naproxen but may cause more minor side effects, suggesting it could be a suitable option among various treatments for arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fenoprofen: a review of its pharmacological properties and therapeutic efficacy in rheumatic diseases. Brogden, RN., Pinder, RM., Speight, TM., et al.[2018]

Ibuprofen, introduced in the late 1960s and 1970s, is an effective anti-inflammatory drug with properties similar to aspirin but with fewer stomach-related side effects, making it a safer option for many patients.

The drug works by inhibiting prostaglandin synthesis, which contributes to its analgesic (pain-relieving) effects, and has been shown to be effective in treating conditions like rheumatoid arthritis and osteoarthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibuprofen. Kantor, TG.[2019]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Outcomes of Prostate-specific Antigen-based Prostate Cancer Screening Among Men Using Nonsteroidal Anti-inflammatory Drugs. [2021]

2. England pubmed.ncbi.nlm.nih.gov

A pilot study of use of the cyclooxygenase-2 inhibitor celecoxib in recurrent prostate cancer after definitive radiation therapy or radical prostatectomy. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Phase III study of ibuprofen versus placebo for radiation-induced genitourinary side effects. [2019]

4. Greece pubmed.ncbi.nlm.nih.gov

Pollen extract in association with vitamins provides early pain relief in patients affected by chronic prostatitis/chronic pelvic pain syndrome. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Phase II trial of celecoxib in prostate-specific antigen recurrent prostate cancer after definitive radiation therapy or radical prostatectomy. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

A fixed-dose combination ibuprofen and famotidine (Duexis). [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Naproxen sodium (Anaprox): pharmacology, pharmacokinetics and drug interactions. [2013]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Naproxen/esomeprazole fixed-dose combination: for the treatment of arthritic symptoms and to reduce the risk of gastric ulcers. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Gastrointestinal tract bleeding associated with naproxen sodium vs ibuprofen. [2013]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of naproxen/esomeprazole magnesium tablets compared with non-specific NSAIDs and COX-2 inhibitors: a systematic review and network analyses. [2020]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetic-pharmacodynamic drug interactions with nonsteroidal anti-inflammatory drugs. [2018]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Fenoprofen: a review of its pharmacological properties and therapeutic efficacy in rheumatic diseases. [2018]

13. United States pubmed.ncbi.nlm.nih.gov

Ibuprofen. [2019]