The Effects of NSAIDs on Bone Metabolism Following Exercise

Study Overview
=================
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.

Official Title
-----------------
The Effects of Non-steroidal Anti-inflammatory Drugs on Circulating Markers of Bone Metabolism Following Plyometric Exercise in Humans

Conditions
-----------------
Bone Resorption, Stress Fracture, Bone Injury

Intervention / Treatment
-----------------
* Drug: Ibuprofen 800 mg
* Drug: Celecoxib 200mg
* Drug: Flurbiprofen 100 mg
* Drug: Placebo


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 42 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 4 trial, block randomized crossover design. Three NSAIDs and one placebo trial.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ibuprofen<br>Participants will consume a single dose of ibuprofen prior to a plyometric exercise bout | Drug: Ibuprofen 800 mg<br>* Ibuprofen taken orally 2 hours prior to exercise<br>* Other names: Motrin;|
| Experimental: Celecoxib<br>Participants will consume a single dose of celecoxib prior to a plyometric exercise bout | Drug: Celecoxib 200mg<br>* Celebrex taken orally 2 hours prior to exercise<br>* Other names: Celebrex;|
| Experimental: Flurbiprofen<br>Participants will consume a single dose of flurbiprofen prior to a plyometric exercise bout | Drug: Flurbiprofen 100 mg<br>* Flurbiprofen taken orally 2 hours prior to exercise<br>* Other names: Ansaid;|
| Placebo Comparator: Placebo<br>Participants will consume a single dose of an inert placebo prior to a plyometric exercise bout | Drug: Placebo<br>* Inert placebo taken orally 2 hours prior to exercise<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline circulating marker of bone resorption | Concentration (pg/mL) of serum C-terminal propeptide of type I collagen (CTX) | 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 | Change from pre-exercise to 3 hours post-exercise |