The Effects of NSAIDs on Bone Metabolism Following Exercise

NCT05512013 | Completed Phase 1 FDA Drug

• 1 other identifier: 21-18H
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Bone Resorption; Stress Fracture; Bone Injury

Outcome Measures

Primary Outcomes (1)

• Change from baseline circulating marker of bone formation

  Concentration (pg/mL) of serum N-terminal propeptide of type 1 collagen (P1NP)

  Change from pre-exercise to 4 hours post-exercise

Secondary Outcomes (2)

• Change from baseline circulating marker of bone resorption

  Change from pre-exercise to 4 hours post-exercise

• Markers of muscle inflammation

  Change from pre-exercise to 3 hours post-exercise

Other Outcomes (1)

• Muscle protein synthesis

  Change from pre-exercise to 3 hours post-exercise

Study Arms (4)

Ibuprofen

EXPERIMENTAL

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

Drug: Ibuprofen 800 mg

Celecoxib

EXPERIMENTAL

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

Drug: Celecoxib 200mg

Flurbiprofen

EXPERIMENTAL

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

Drug: Flurbiprofen 100 mg

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Ibuprofen 800 mg DRUG

Ibuprofen taken orally 2 hours prior to exercise

Also known as: Advil, Motrin

Ibuprofen

Celecoxib 200mg DRUG

Celebrex taken orally 2 hours prior to exercise

Also known as: Celebrex

Celecoxib

Flurbiprofen 100 mg DRUG

Flurbiprofen taken orally 2 hours prior to exercise

Also known as: Ansaid

Flurbiprofen

Placebo DRUG

Inert placebo taken orally 2 hours prior to exercise

Placebo

Eligibility Criteria

• Age: 18 Years - 42 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• United States Army Research Institute of Environmental Medicine: lead

Study Sites (1)

United States Army Research Institute of Environmental Medicine

Natick, Massachusetts, 01760, United States

Location

Related Publications (6)

• 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.

  PMID: 33641442 BACKGROUND

• Jankowski 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.

  PMID: 25642444 BACKGROUND

• Kohrt 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.

  PMID: 20200939 BACKGROUND

• Wherry 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.

  PMID: 33876259 BACKGROUND

• Brewer 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.

  PMID: 26289996 BACKGROUND

• Park 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.

  PMID: 30998998 BACKGROUND

MeSH Terms

Conditions

Bone Resorption; Fractures, Stress

Interventions

Ibuprofen; Celecoxib; Flurbiprofen

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases; Fractures, Bone; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzenesulfonamides; Sulfonamides; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Propionates; Acids, Acyclic; Biphenyl Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 4 trial, block randomized crossover design. Three NSAIDs and one placebo trial.

Study Record Dates

• First Submitted: August 16, 2022
• First Posted: August 23, 2022
• Study Start: February 15, 2022
• Primary Completion: April 1, 2023
• Study Completion: April 1, 2023
• Last Updated: November 29, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)