Bone ResorptionPhase 1NCT05512013
The Effects of NSAIDs on Bone Metabolism Following Exercise
A Phase 1 study testing Ibuprofen 800 mg, Celecoxib 200mg and Flurbiprofen 100 mg in people with Bone Resorption and Stress Fracture, run by United States Army Research Institute of Environmental Medicine at 1 site in United States.
Trial summary
The purpose of this study is to determine the effects of a single dose of non-steroidal anti-inflammatory drugs on post-exercise markers of bone and muscle metabolism. Read more about this study
- Who is it for?
- Ages 18 to 42 yearsHealthy volunteers can take part
- Conditions the study is for
- Bone Resorption, Stress Fracture, Bone Injury
- What is being tested?
- Ibuprofen 800 mg, Celecoxib 200mg and Flurbiprofen 100 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Feb 2022to 1 Apr 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 42 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Must currently exercise at least 2 times per week
- 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
- Must be willing to refrain from taking NSAIDs and similar medications during the course of the study (other than those given by the study team)
- Weigh at least 110 lbs and have a hemoglobin of 12.5 g/dL or higher
Who cannot join
- Known allergic reaction to any NSAID type medication
- History of gastrointestinal disorders/discomfort associated with or which may be aggravated with NSAID use
- History or known gastric ulcer
- History of endocrine disorders (e.g., diabetes, uncontrolled thyroid dysfunction, hypoparathyroidism, or hyperparathyroidism)
- History of bone-modifying disorder (e.g., osteogenesis imperfecta, osteoporosis, or rickets)
- Diagnosed bone fracture within last 6 months
Show all 13Show fewer
- History of cardiovascular or renal diseases
- Pregnant or lactation in the last 6 months
- Currently taking or history of routine use of medications known to affect bone or calcium metabolism (e.g., thiazide diuretics, bisphosphonates, oral steroids)
- History of back or shoulder injury which may be aggravated by exercise
- Blood donation within 8 weeks of the study
- Current physical illness or injury limiting physical activity
- Known allergy to lidocaine
Trial locations and contacts
1 site in 1 country.
United States1 site
United States Army Research Institute of Environmental Medicine
Natick, Massachusetts, 01760
About this study
Official title: The Effects of Non-steroidal Anti-inflammatory Drugs on Circulating Markers of Bone Metabolism Following Plyometric Exercise in Humans
The purpose of this study is to determine the effects of a single dose of non-steroidal anti-inflammatory drugs on post-exercise markers of bone and muscle metabolism.
Read the detailed description
This protocol intends to determine how consuming a single dose of a non-steroidal anti-inflammatory drug (NSAID) affects circulating bone metabolism biomarkers and markers of damage skeletal muscle in response to a bout of plyometric exercise. This will be accomplished using a four trial, placebo-controlled crossover design with trials examining ibuprofen, celecoxib, flurbiprofen and placebo. These particular NSAIDs were chosen because of their widespread use in military populations and differing molecular mechanisms, which could cause differing effects on bone and muscle. Two hours after of consuming a single dose of an NSAID, participants will perform 10 sets of 10 plyometric jumps to induce a mechanical loading stimulus the bone and muscle tissues. Blood, urine, and muscle biopsy samples will be collected before and up to four hours after exercise. Biomarkers representing bone and muscle metabolism will determine the magnitude of adaptive responses to plyometric exercise while using NSAIDs.
- Conditions
- Bone Resorption, Stress Fracture, Bone Injury
- Being tested
- Ibuprofen 800 mg, Celecoxib 200mg, Flurbiprofen 100 mg, Placebo
- Medical subject headings
- Bone Resorption, Fractures, Stress
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ibuprofen 800 mgDrug
Also called Advil, Motrin
Ibuprofen taken orally 2 hours prior to exercise
Celecoxib 200mgDrug
Also called Celebrex
Celebrex taken orally 2 hours prior to exercise
Flurbiprofen 100 mgDrug
Also called Ansaid
Flurbiprofen taken orally 2 hours prior to exercise
PlaceboDrug
Inert placebo taken orally 2 hours prior to exercise
| Study group | Role | What they receive |
|---|---|---|
| Ibuprofen | Experimental | Participants will consume a single dose of ibuprofen prior to a plyometric exercise bout Receives: Drug: Ibuprofen 800 mg |
| Celecoxib | Experimental | Participants will consume a single dose of celecoxib prior to a plyometric exercise bout Receives: Drug: Celecoxib 200mg |
| Flurbiprofen | Experimental | Participants will consume a single dose of flurbiprofen prior to a plyometric exercise bout Receives: Drug: Flurbiprofen 100 mg |
| Placebo | Placebo comparator | Participants will consume a single dose of an inert placebo prior to a plyometric exercise bout Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline circulating marker of bone formation
Concentration (pg/mL) of serum N-terminal propeptide of type 1 collagen (P1NP)
Measured: Change from pre-exercise to 4 hours post-exercise
Secondary outcomes (2)
Change from baseline circulating marker of bone resorption
Concentration (pg/mL) of serum C-terminal propeptide of type I collagen (CTX)
Measured: Change from pre-exercise to 4 hours post-exercise
Markers of muscle inflammation
Interlukin-6 (IL-6), Interlukin-10 (IL-10), and tissue necrosis factor (TNF-a) messenger ribonucleic acid (mRNA) concentration in muscle biopsy tissue
Measured: Change from pre-exercise to 3 hours post-exercise
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2022
- Study start15 Feb 2022
- Primary completion1 Apr 2023
- Study completion1 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Bone ResorptionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 4 trial, block randomized crossover design. Three NSAIDs and one placebo trial.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- United States Army Research Institute of Environmental Medicine
- Sponsor type
- US federal agency
- Responsible party
- Principal investigator, Jeffery Staab, United States Army Research Institute of Environmental Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05512013
- Sponsor's protocol ID
- 21-18H
- Status last verified
- Nov 2023
- First submitted
- 16 Aug 2022
- Last updated
- 29 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Staab JS, Kolb AL, Tomlinson RE, Pajevic PD, Matheny RW Jr, Hughes JM. Emerging evidence that adaptive bone formation inhibition by non-steroidal anti-inflammatory drugs increases stress fracture risk. Exp Biol Med (Maywood). 2021 May;246(9):1104-1111. doi: 10.1177/1535370221993098. Epub 2021 Feb 27.
PubMed 33641442Jankowski CM, Shea K, Barry DW, Linnebur SA, Wolfe P, Kittelson J, Schwartz RS, Kohrt WM. Timing of Ibuprofen Use and Musculoskeletal Adaptations to Exercise Training in Older Adults. Bone Rep. 2015 Jan 1;1:1-8. doi: 10.1016/j.bonr.2014.10.003.
PubMed 25642444Kohrt WM, Barry DW, Van Pelt RE, Jankowski CM, Wolfe P, Schwartz RS. Timing of ibuprofen use and bone mineral density adaptations to exercise training. J Bone Miner Res. 2010 Jun;25(6):1415-22. doi: 10.1002/jbmr.24.
PubMed 20200939Wherry SJ, Wolfe P, Schwartz RS, Kohrt WM, Jankowski CM. Ibuprofen taken before exercise blunts the IL-6 response in older adults but does not alter bone alkaline phosphatase or c-telopeptide. Eur J Appl Physiol. 2021 Aug;121(8):2187-2192. doi: 10.1007/s00421-021-04691-8. Epub 2021 Apr 19.
PubMed 33876259Brewer CB, Bentley JP, Day LB, Waddell DE. Resistance exercise and naproxen sodium: effects on a stable PGF2alpha metabolite and morphological adaptations of the upper body appendicular skeleton. Inflammopharmacology. 2015 Dec;23(6):319-27. doi: 10.1007/s10787-015-0248-x. Epub 2015 Aug 20.
PubMed 26289996Park J, Fertala A, Tomlinson RE. Naproxen impairs load-induced bone formation, reduces bone toughness, and diminishes woven bone formation following stress fracture in mice. Bone. 2019 Jul;124:22-32. doi: 10.1016/j.bone.2019.04.009. Epub 2019 Apr 15.
PubMed 30998998
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Non-steroidal Anti-inflammatory Drugs on Circulating Markers of Bone Metabolism Following Plyometric Exercise in Humans
- ClinicalTrials.gov ID
- NCT05512013
- Acronym / sponsor ID
- 21-18H
- Conditions
- Bone Resorption, Stress Fracture, Bone Injury
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- United States Army Research Institute of Environmental MedicineUS federal agency
- Study start
- 15 Feb 2022 (actual)
- Primary completion
- 1 Apr 2023 (actual)
- Study completion
- 1 Apr 2023 (actual)
- First posted
- 23 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the effects of a single dose of non-steroidal anti-inflammatory drugs on post-exercise markers of bone and muscle metabolism.
Detailed description
This protocol intends to determine how consuming a single dose of a non-steroidal anti-inflammatory drug (NSAID) affects circulating bone metabolism biomarkers and markers of damage skeletal muscle in response to a bout of plyometric exercise. This will be accomplished using a four trial, placebo-controlled crossover design with trials examining ibuprofen, celecoxib, flurbiprofen and placebo. These particular NSAIDs were chosen because of their widespread use in military populations and differing molecular mechanisms, which could cause differing effects on bone and muscle. Two hours after of consuming a single dose of an NSAID, participants will perform 10 sets of 10 plyometric jumps to induce a mechanical loading stimulus the bone and muscle tissues. Blood, urine, and muscle biopsy samples will be collected before and up to four hours after exercise. Biomarkers representing bone and muscle metabolism will determine the magnitude of adaptive responses to plyometric exercise while using NSAIDs.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- 4 trial, block randomized crossover design. Three NSAIDs and one placebo trial.
| Arm | Type | Receives |
|---|---|---|
| Ibuprofen | Experimental | Drug: Ibuprofen 800 mgParticipants will consume a single dose of ibuprofen prior to a plyometric exercise bout |
| Celecoxib | Experimental | Drug: Celecoxib 200mgParticipants will consume a single dose of celecoxib prior to a plyometric exercise bout |
| Flurbiprofen | Experimental | Drug: Flurbiprofen 100 mgParticipants will consume a single dose of flurbiprofen prior to a plyometric exercise bout |
| Placebo | Placebo comparator | Drug: PlaceboParticipants will consume a single dose of an inert placebo prior to a plyometric exercise bout |
Who may qualify
- Ages
- 18 to 42 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Must currently exercise at least 2 times per week
- 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
- Must be willing to refrain from taking NSAIDs and similar medications during the course of the study (other than those given by the study team)
- Weigh at least 110 lbs and have a hemoglobin of 12.5 g/dL or higher
Key exclusion criteria (13 listed)
- Known allergic reaction to any NSAID type medication
- History of gastrointestinal disorders/discomfort associated with or which may be aggravated with NSAID use
- History or known gastric ulcer
- History of endocrine disorders (e.g., diabetes, uncontrolled thyroid dysfunction, hypoparathyroidism, or hyperparathyroidism)
- History of bone-modifying disorder (e.g., osteogenesis imperfecta, osteoporosis, or rickets)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ibuprofen 800 mgAlso: Advil, MotrinIbuprofen taken orally 2 hours prior to exercise | Drug | Ibuprofen |
| Celecoxib 200mgAlso: CelebrexCelebrex taken orally 2 hours prior to exercise | Drug | Celecoxib |
| Flurbiprofen 100 mgAlso: AnsaidFlurbiprofen taken orally 2 hours prior to exercise | Drug | Flurbiprofen |
| PlaceboInert placebo taken orally 2 hours prior to exercise | Drug | Placebo |
Primary outcome
Change from baseline circulating marker of bone formation
Time frame: Change from pre-exercise to 4 hours post-exercise
Concentration (pg/mL) of serum N-terminal propeptide of type 1 collagen (P1NP)
2 secondary outcomes
Change from baseline circulating marker of bone resorption
Time frame: Change from pre-exercise to 4 hours post-exercise
Markers of muscle inflammation
Time frame: Change from pre-exercise to 3 hours post-exercise
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2023.
- Background: PubMed 33641442Staab JS, Kolb AL, Tomlinson RE, Pajevic PD, Matheny RW Jr, Hughes JM. Emerging evidence that adaptive bone formation inhibition by non-steroidal anti-inflammatory drugs increases stress fracture risk. Exp Biol Med (Maywood). 2021 May;246(9):1104-1111. doi: 10.1177/1535370221993098. Epub 2021 Feb 27.
- Background: PubMed 25642444Jankowski CM, Shea K, Barry DW, Linnebur SA, Wolfe P, Kittelson J, Schwartz RS, Kohrt WM. Timing of Ibuprofen Use and Musculoskeletal Adaptations to Exercise Training in Older Adults. Bone Rep. 2015 Jan 1;1:1-8. doi: 10.1016/j.bonr.2014.10.003.
- Background: PubMed 20200939Kohrt WM, Barry DW, Van Pelt RE, Jankowski CM, Wolfe P, Schwartz RS. Timing of ibuprofen use and bone mineral density adaptations to exercise training. J Bone Miner Res. 2010 Jun;25(6):1415-22. doi: 10.1002/jbmr.24.
- Background: PubMed 33876259Wherry SJ, Wolfe P, Schwartz RS, Kohrt WM, Jankowski CM. Ibuprofen taken before exercise blunts the IL-6 response in older adults but does not alter bone alkaline phosphatase or c-telopeptide. Eur J Appl Physiol. 2021 Aug;121(8):2187-2192. doi: 10.1007/s00421-021-04691-8. Epub 2021 Apr 19.
- Background: PubMed 26289996Brewer CB, Bentley JP, Day LB, Waddell DE. Resistance exercise and naproxen sodium: effects on a stable PGF2alpha metabolite and morphological adaptations of the upper body appendicular skeleton. Inflammopharmacology. 2015 Dec;23(6):319-27. doi: 10.1007/s10787-015-0248-x. Epub 2015 Aug 20.
- Background: PubMed 30998998Park J, Fertala A, Tomlinson RE. Naproxen impairs load-induced bone formation, reduces bone toughness, and diminishes woven bone formation following stress fracture in mice. Bone. 2019 Jul;124:22-32. doi: 10.1016/j.bone.2019.04.009. Epub 2019 Apr 15.
- Individual participant dataSharing planned: No
Related trials for Bone Resorption
Active, not recruiting
L-PRF Block vs Composite Graft for Horizontal Ridge Augmentation
Alveolar Ridge Resorption After Extraction, Alveolar Bone Loss
Active, not recruiting
Optimal Meals to Reduce Bone Resorption in Women With Osteopenia
Osteopenia
Not yet recruitingObservational study
Diagnostic Accuracy of Large Language Models for Peri-Implant Marginal Bone Loss on Panoramic Radiographs
Peri-implantitis, Alveolar Bone Loss
Recruiting
Two Bovine Xenografts in Lateral Window Sinus Augmentation With or Without Bone Marrow Blood
Alveolar Bone Loss, Sinus Floor Augmentation
Recruiting
The Application of a Biphasic Calcium Sulfate Graft Material in Sinus Floor Elevation
Alveolar Bone Loss, Edentulism Nos
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ibuprofen 800 mg, Celecoxib 200mg and Flurbiprofen 100 mg in people with Bone Resorption and Stress Fracture, run by United States Army Research Institute of Environmental Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline circulating marker of bone formation (time frame: Change from pre-exercise to 4 hours post-exercise). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05512013, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2023.