The Effects of NSAIDs on Bone Metabolism Following Exercise

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

12 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug in the clinical trial?

Research shows that flurbiprofen is effective as a pain reliever and anti-inflammatory, often performing as well as or better than other similar drugs like ibuprofen and naproxen for conditions like rheumatoid arthritis and osteoarthritis. This suggests that the drug being tested, which includes flurbiprofen, may also be effective for these conditions. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

Ibuprofen is generally considered safe for humans, with rare adverse effects reported. Flurbiprofen, while effective, has been associated with severe skin reactions and hypersensitivity in rare cases, and like other similar drugs, can cause gastrointestinal and kidney side effects. ^{1 6 7 8 9}

How does this drug differ from other pain relief drugs?

This drug, lornoxicam, is unique because it is used as an injectable form for acute postoperative pain relief, which may offer faster pain relief compared to oral medications like diclofenac, ketoprofen, and dipyrone. ^{5 10 11 12 13}

What is the purpose of this trial?

This trial tests common pain relievers on people who do intense jumping exercises to see how these drugs affect bone and muscle health. It focuses on military personnel because they often use these medications. Researchers will measure changes in the body to understand the effects.

Eligibility Criteria

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

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)

Treatment Details

Interventions

• Celecoxib
• Flurbiprofen
• Ibuprofen
• Placebo

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

References

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

European experience with flurbiprofen. A new analgesic/anti-inflammatory agent. [2022]

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

Efficacy of single-dose and multidose rofecoxib in the treatment of post-orthopedic surgery pain. [2014]

3. England pubmed.ncbi.nlm.nih.gov

Three trials of indoprofen. [2013]

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

Use of ibuprofen in unusual circumstances. [2019]

5. Canada 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. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Diagnosis and treatment of flurbiprofen-induced Stevens-Johnson syndrome: A rare case report. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Fatal hypersensitivity reaction to an oral spray of flurbiprofen: a case report. [2013]

8. England pubmed.ncbi.nlm.nih.gov

Adverse reactions to indoprofen: a survey based on a total of 6764 patients. [2017]

9. Poland pubmed.ncbi.nlm.nih.gov

Safety of oral ibuprofen--analysis of data from the spontaneous reporting system in Poland. [2022]

10. England pubmed.ncbi.nlm.nih.gov

A placebo and active comparator-controlled trial of rofecoxib for the treatment of rheumatoid arthritis. [2019]

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

Incidence of outpatient physician claims for upper gastrointestinal symptoms among new users of celecoxib, ibuprofen, and naproxen in an insured population in the United States. [2015]

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

Efficacy of lornoxicam for acute postoperative pain relief after septoplasty: a comparison with diclofenac, ketoprofen, and dipyrone. [2022]

13. Germany pubmed.ncbi.nlm.nih.gov

Lumiracoxib is effective in the treatment of osteoarthritis of the knee: a prospective randomized 13-week study versus placebo and celecoxib. [2022]