The Effects of NSAIDs on Bone Metabolism Following Exercise
Primary Purpose
Bone Resorption, Stress Fracture, Bone Injury
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ibuprofen 800 mg
Celecoxib 200mg
Flurbiprofen 100 mg
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Bone Resorption
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Sites / Locations
- United States Army Research Institute of Environmental MedicineRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
Ibuprofen
Celecoxib
Flurbiprofen
Placebo
Arm Description
Participants will consume a single dose of ibuprofen prior to a plyometric exercise bout
Participants will consume a single dose of celecoxib prior to a plyometric exercise bout
Participants will consume a single dose of flurbiprofen prior to a plyometric exercise bout
Participants will consume a single dose of an inert placebo prior to a plyometric exercise bout
Outcomes
Primary Outcome Measures
Change from baseline circulating marker of bone formation
Concentration (pg/mL) of serum N-terminal propeptide of type 1 collagen (P1NP)
Secondary Outcome Measures
Change from baseline circulating marker of bone resorption
Concentration (pg/mL) of serum C-terminal propeptide of type I collagen (CTX)
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
Full Information
NCT ID
NCT05512013
First Posted
August 16, 2022
Last Updated
August 19, 2022
Sponsor
United States Army Research Institute of Environmental Medicine
1. Study Identification
Unique Protocol Identification Number
NCT05512013
Brief Title
The Effects of NSAIDs on Bone Metabolism Following Exercise
Official Title
The Effects of Non-steroidal Anti-inflammatory Drugs on Circulating Markers of Bone Metabolism Following Plyometric Exercise in Humans
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 15, 2022 (Actual)
Primary Completion Date
April 1, 2023 (Anticipated)
Study Completion Date
April 1, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
United States Army Research Institute of Environmental Medicine
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bone Resorption, Stress Fracture, Bone Injury
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Model Description
4 trial, block randomized crossover design. Three NSAIDs and one placebo trial.
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Ibuprofen
Arm Type
Experimental
Arm Description
Participants will consume a single dose of ibuprofen prior to a plyometric exercise bout
Arm Title
Celecoxib
Arm Type
Experimental
Arm Description
Participants will consume a single dose of celecoxib prior to a plyometric exercise bout
Arm Title
Flurbiprofen
Arm Type
Experimental
Arm Description
Participants will consume a single dose of flurbiprofen prior to a plyometric exercise bout
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will consume a single dose of an inert placebo prior to a plyometric exercise bout
Intervention Type
Drug
Intervention Name(s)
Ibuprofen 800 mg
Other Intervention Name(s)
Advil, Motrin
Intervention Description
Ibuprofen taken orally 2 hours prior to exercise
Intervention Type
Drug
Intervention Name(s)
Celecoxib 200mg
Other Intervention Name(s)
Celebrex
Intervention Description
Celebrex taken orally 2 hours prior to exercise
Intervention Type
Drug
Intervention Name(s)
Flurbiprofen 100 mg
Other Intervention Name(s)
Ansaid
Intervention Description
Flurbiprofen taken orally 2 hours prior to exercise
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Inert placebo taken orally 2 hours prior to exercise
Primary Outcome Measure Information:
Title
Change from baseline circulating marker of bone formation
Description
Concentration (pg/mL) of serum N-terminal propeptide of type 1 collagen (P1NP)
Time Frame
Change from pre-exercise to 4 hours post-exercise
Secondary Outcome Measure Information:
Title
Change from baseline circulating marker of bone resorption
Description
Concentration (pg/mL) of serum C-terminal propeptide of type I collagen (CTX)
Time Frame
Change from pre-exercise to 4 hours post-exercise
Title
Markers of muscle inflammation
Description
Interlukin-6 (IL-6), Interlukin-10 (IL-10), and tissue necrosis factor (TNF-a) messenger ribonucleic acid (mRNA) concentration in muscle biopsy tissue
Time Frame
Change from pre-exercise to 3 hours post-exercise
Other Pre-specified Outcome Measures:
Title
Muscle protein synthesis
Description
ribosomal protein S6 (p-RPS6) protein concentration in muscle biopsy tissue
Time Frame
Change from pre-exercise to 3 hours post-exercise
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
42 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jeffery Staab, MS
Phone
508-206-2393
Email
jeffery.s.staab.civ@health.mil
Facility Information:
Facility Name
United States Army Research Institute of Environmental Medicine
City
Natick
State/Province
Massachusetts
ZIP/Postal Code
01760
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jeffery Staab, MS
Phone
508-206-2393
Email
jeffery.s.staab.civ@health.mil
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
33641442
Citation
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.
Results Reference
background
PubMed Identifier
25642444
Citation
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.
Results Reference
background
PubMed Identifier
20200939
Citation
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.
Results Reference
background
PubMed Identifier
33876259
Citation
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.
Results Reference
background
PubMed Identifier
26289996
Citation
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.
Results Reference
background
PubMed Identifier
30998998
Citation
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.
Results Reference
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The Effects of NSAIDs on Bone Metabolism Following Exercise
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