NSAIDs for Bone Health

Overseen By Jeffery Staab, MS

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: United States Army Research Institute of Environmental Medicine

Must not be taking: Thiazides, Bisphosphonates, Steroids

Disqualifiers: Diabetes, Osteoporosis, Cardiovascular, others

Compensation: Varies

Number of Visits: 2

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different non-steroidal anti-inflammatory drugs (NSAIDs) affect bones and muscles after exercise. The medications tested include Celecoxib (Celebrex), Flurbiprofen, and Ibuprofen, along with a placebo for comparison. The goal is to determine how a single dose of these drugs influences the body's bone and muscle processes post-workout. Individuals who exercise at least twice a week and are willing to adjust their supplement and medication use may be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

Will I have to stop taking my current medications?

You will need to stop taking NSAIDs and similar medications during the study, except for those provided by the study team. The protocol does not specify about other medications, but you must stop using nutritional supplements, alcohol, and nicotine during each study period unless approved by the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found that ibuprofen was generally well-tolerated, but it may cause stomach issues or allergic reactions in people sensitive to aspirin. Celecoxib has been linked to a higher risk of serious heart problems, such as heart attacks and strokes. It may also cause bleeding in the stomach or intestines, sometimes without warning signs. Flurbiprofen can be harmful if swallowed or if it contacts the skin, and it might also irritate the skin or eyes. Each of these medications is already approved for other uses, providing some evidence of safety, but side effects can still occur. Always consult a healthcare provider to weigh the risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore how different NSAIDs—like ibuprofen, celecoxib, and flurbiprofen—affect bone metabolism after exercise. Normally, NSAIDs are used to relieve pain and inflammation, but this trial aims to see if they also influence how bones respond to physical stress. Each NSAID might interact differently with bone tissues, offering insights into which one could potentially aid in faster recovery or improved bone health. This could lead to more personalized approaches in managing exercise-related bone stress, beyond just pain relief.

What evidence suggests that this trial's treatments could be effective for post-exercise bone and muscle metabolism?

This trial will compare the effects of ibuprofen, celecoxib, and flurbiprofen, each taken as a single dose before a plyometric exercise bout, with a placebo. Research has shown that taking ibuprofen before exercise doesn't significantly alleviate muscle soreness or enhance performance and might slow the body's natural healing process. Celecoxib, another treatment option in this trial, appears ineffective in reducing swelling or muscle damage after exercise. Flurbiprofen, also being tested, doesn't significantly impact soreness or recovery. Overall, studies suggest these medications might not effectively ease muscle issues after exercise. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

Inclusion Criteria

You must be currently exercising at least twice a week.

You cannot take certain pain-relieving medications, such as aspirin or ibuprofen, unless specifically instructed by the study team.

Must be willing to discontinue the use of nutritional supplements, alcohol and nicotine during each study period (4 trials of 5 consecutive days each), unless approved by PI

Exclusion Criteria

You have a history of stomach ulcers.

You have a past injury in your back or shoulder that may get worse with exercise.

You have experienced stomach problems or discomfort in the past when taking drugs like aspirin or ibuprofen.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants consume a single dose of NSAID or placebo and perform plyometric exercise

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in circulating markers of bone and muscle metabolism

4 hours

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Celecoxib
• Flurbiprofen
• Ibuprofen
• Placebo

How Is the Trial Designed?

Group I: Ibuprofen Experimental Treatment 1 Intervention

Participants will consume a single dose of ibuprofen prior to a plyometric exercise bout

Group II: Flurbiprofen Experimental Treatment 1 Intervention

Participants will consume a single dose of flurbiprofen prior to a plyometric exercise bout

Group III: Celecoxib Experimental Treatment 1 Intervention

Participants will consume a single dose of celecoxib prior to a plyometric exercise bout

Group IV: Placebo Placebo Group 1 Intervention

Participants will consume a single dose of an inert placebo prior to a plyometric exercise bout

Who Is Running the Clinical Trial?

United States Army Research Institute of Environmental Medicine

Lead Sponsor

Trials

67

Recruited

3,700+

Published Research Related to This Trial

Over a 10-year period, a total of 29,656,286 units of various ibuprofen formulations were sold in Poland, with only 5 spontaneous reports of adverse effects, indicating that ibuprofen is a very safe medication with rare side effects.

The study suggests that while ibuprofen is generally safe, the current monitoring system for adverse effects in Poland is insufficient and requires enhancements to better detect potential issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of oral ibuprofen--analysis of data from the spontaneous reporting system in Poland. Kuchari, E., Han, S., Karłowicz-Bodalska, K., et al.[2022]

Ibuprofen is effective in managing pain and inflammation, but its use requires careful consideration in patients with certain conditions, such as renal disease and bleeding disorders, due to its effects on prostaglandins.

The drug can be safely used in various patient populations, including the elderly and those with specific diseases, but clinicians should be cautious when prescribing it alongside other medications like aspirin or warfarin, as interactions may occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of ibuprofen in unusual circumstances. Furst, DE.[2019]

Flurbiprofen has been proven safe and effective as an analgesic, anti-inflammatory, and antipyretic agent in numerous European clinical trials over the past 12 years, showing it is at least as potent as indomethacin and significantly more potent than aspirin.

In patients with rheumatoid arthritis and ankylosing spondylitis, flurbiprofen demonstrated superior or equivalent efficacy compared to other common treatments like aspirin, naproxen, and indomethacin, with minimal gastrointestinal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European experience with flurbiprofen. A new analgesic/anti-inflammatory agent. Buchanan, WW., Kassam, YB.[2022]

In a study involving 444 patients with knee osteoarthritis, both naproxen sodium (660 mg and 440 mg for older patients) and ibuprofen (1200 mg) were found to significantly relieve pain compared to placebo, with naproxen showing a greater reduction in symptoms overall.

Naproxen sodium was particularly effective for night-time pain relief and improved all assessed symptoms compared to placebo, while both medications had similar safety profiles with no significant differences in adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the analgesic efficacy and safety of nonprescription doses of naproxen sodium and Ibuprofen in the treatment of osteoarthritis of the knee. Schiff, M., Minic, M.[2022]

In a study involving 200 patients undergoing elective septoplasty, lornoxicam was found to be effective in managing acute postoperative pain, but its efficacy was not superior to that of other nonopioid analgesics like diclofenac, ketoprofen, and dipyrone.

Patients receiving placebo required significantly more additional analgesia (pethidine) compared to those receiving active treatments, indicating that all active medications provided better pain relief than placebo, with no significant differences in adverse effects among the treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of lornoxicam for acute postoperative pain relief after septoplasty: a comparison with diclofenac, ketoprofen, and dipyrone. Sener, M., Yilmazer, C., Yilmaz, I., et al.[2022]

In a phase 4 study involving 4042 patients with osteoarthritis, indoprofen was generally well-tolerated, with adverse events occurring in 22% of patients, and less than 5% needing to stop treatment due to drug-related issues.

The safety profile of indoprofen showed that gastrointestinal issues were the most common side effects, similar to other NSAIDs, and tolerability was better with parenteral administration compared to oral, especially at higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse reactions to indoprofen: a survey based on a total of 6764 patients. Bruni, G., Lavezzari, M., Perbellini, A., et al.[2017]

Citations

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Taken together, these data indicate that the plyometric exercise caused muscle soreness, but no NSAIDs improved muscle soreness 4- or 24-h post-exercise.

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Our results indicate that celecoxib use following exercise does not alleviate inflammation, muscle damage, or oxidative stress.

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NSAIDs do not prevent exercise-induced performance deficits or alleviate muscle soreness: A placebo-controlled randomized, double-blinded, cross ...

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Muscle soreness and rhabdomyolysis

The soreness that commonly follows unaccustomed and strenuous exercise is unlikely to be due to inflammation of the muscles.

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Use personal protective equipment as required. Avoid dust formation. Keep people away from and upwind of spill/leak. Evacuate personnel to safe.

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