Myogenic and Osteogenic Responses to eXercise and Ibuprofen

Study Overview
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Brief Summary
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The purpose of this study is to determine if the use of ibuprofen blocks the benefits of exercise to build bone and muscle mass.

Detailed Description
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People are advised to engage in weight-bearing physical activity to help prevent the loss of bone and muscle mass that occurs with aging. There is evidence from studies of animals that non-steroidal anti-inflammatory drugs (NSAIDS), such as ibuprofen, block some of the bone- and muscle-building effects of exercise. The aim of this study is to determine whether use of ibuprofen, either before or after exercise, blocks the benefits of exercise training on bone and skeletal muscle in older women and men. The hypothesis is that taking ibuprofen before exercise will block some of the effects of exercise training to increase bone density and muscle mass. Women and men aged 60-75 years will complete a supervised, 9-month exercise training program designed to increase bone and muscle mass. The training will include weight lifting and weight-bearing exercises, such as jumping in place and treadmill walking, up to 5 days per week. Participants will be randomly assigned to take 1 of 3 study pill combinations before and after each exercise session. The combinations of study pills will be: placebo before/placebo after, placebo before/ibuprofen after, or ibuprofen before/placebo after. The dose of ibuprofen will be 400 mg. Bone density of the hip and spine, body composition (total body muscle and fat), and markers of bone turnover in the blood will be measured before and after 4.5 and 9 months of training. Muscle cross-sectional area of the thigh will be measured by CT before and after 9 months of training. A subset of participants will have biopsies of the thigh muscle before and after training to measure proteins and genes associated with muscle build-up and breakdown. Volunteers who do not use ibuprofen, aspirin, or acetaminophen more than 3 days per month will be enrolled. People with intolerance to ibuprofen or related drugs, cardiovascular disease, or orthopedic problems that limit exercise will be excluded from the study.

Official Title
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COX Inhibition & Musculoskeletal Responses to Exercise

Conditions
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Aging, Physical Fitness

Intervention / Treatment
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* Drug: Ibuprofen
* Drug: Placebo
* Behavioral: musculoskeletal-loading exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 60 to 75 years Willing to participate in a 9-month supervised exercise program that will start at a moderate intensity and gradually progress to a vigorous intensity Not currently performing regular, moderate-to-vigorous weight-bearing or weight-lifting exercise Average use of NSAIDs (including low-dose aspirin) or acetaminophen less than 3 days per month Exclusion Criteria: Relative or absolute contraindications to regular use of NSAIDs Known allergy or intolerance (heartburn, stomach pain, nausea, vomiting) to NSAIDs; controlled GERD(Gastroesophageal Reflux Disease), if not related to NSAID use, will not be an exclusion criterion Proton Pump Inhibitor (PPI) use if dose is unstable or if using for less than 6 months prior to study enrollment History of peptic ulcer or upper GI bleeding Anemia Asthma with bronchospasm induced by aspirin or other NSAIDs Moderate or severe renal impairment defined as a calculated creatinine clearance Chronic hepatobiliary disease, conservatively defined as liver function tests greater than 1.5 times the upper limit of normal (if such values are obtained on initial screening and thought to be transient in nature, repeated testing will be allowed) Hyperkalemia Osteoporosis Diabetes mellitus requiring pharmacologic therapy Congestive heart failure Uncontrolled hypertension; use of thiazide diuretics will be allowed if on a stable dose for at least 6 months Cardiovascular disease Thyroid dysfunction Orthopedic problems (e.g., chronic back pain, severe osteoarthritis, rheumatoid arthritis) that limit the ability to perform vigorous exercise and increase the likelihood that the volunteer will use pain medications other than the study pills Certain use of medications, including Drugs that are known to alter bone metabolism (e.g., estrogen, SERMs(Selective estrogen-receptor modulators), testosterone, bisphosphonates, teriparatide, calcitonin, GnRH(Gonadotropin-releasing hormone) agonists) Chronic use of oral corticosteroids or any use in the previous 6 months (use of inhaled steroids will not be an exclusion criterion based on a meta-analysis documenting that the effect on bone is not significant) Average use of acetaminophen or NSAIDs, including low-dose aspirin, greater than 3 days per month; volunteers using aspirin for primary prevention may enroll in the study if they discontinue aspirin therapy for the 9-month intervention period Anticoagulants (e.g., warfarin, clopidogrel) Narcotics

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo pre and post exercise<br>placebo before and after musculoskeletal-loading exercise | Drug: Placebo<br>* with each exercise session (up to 5 days per week) for 9 months<br>Behavioral: musculoskeletal-loading exercise<br>* Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months<br>|
| Experimental: Placebo pre and ibuprofen post exercise<br>placebo before and ibuprofen after musculoskeletal-loading exercise | Drug: Ibuprofen<br>* 400 mg with each exercise session (up to 5 days per week) for 9 months<br>* Other names: Advil;Drug: Placebo<br>* with each exercise session (up to 5 days per week) for 9 months<br>Behavioral: musculoskeletal-loading exercise<br>* Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months<br>|
| Experimental: Ibuprofen pre and placebo post exercise<br>ibuprofen before and placebo after musculoskeletal-loading exercise | Drug: Ibuprofen<br>* 400 mg with each exercise session (up to 5 days per week) for 9 months<br>* Other names: Advil;Drug: Placebo<br>* with each exercise session (up to 5 days per week) for 9 months<br>Behavioral: musculoskeletal-loading exercise<br>* Exercise training program designed to increase bone and muscle mass, including weight lifting and weight-bearing exercises such as jumping in place and treadmill walking up to 5 days per week for 9 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 9 Months |  | Baseline and after 9 months of training | 
| Percentage Change From Baseline in Total Hip Bone Mineral Density (BMD) at 9 Months |  | Baseline and after 9 months of training | 
| Change From Baseline in Fat-free Mass at 9 Months |  | Baseline and after 9 months of training | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at 9 Months |  | Baseline and after 9 months of training | 
| Percentage Change From Baseline in Trochanter Bone Mineral Density (BMD) at 9 Months |  | Baseline and after 9 months of training | 
| Percentage Change From Baseline in Sub-trochanter Bone Mineral Density (BMD) at 9 Months |  | Baseline and after 9 months of training | 
| Change in Thigh Cross-sectional Muscle Area |  | Baseline and after 9 months of training | 
| Bone Turnover Markers |  | Baseline, and after 4.5 & 9 months of training | 
| Expression of Selected Proteins and Genes Associated With Muscle Build-up and Breakdown |  | Baseline and after 9 months of training | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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body composition, bone density, cyclooxygenase inhibitor, bone metabolism, muscle function, muscle strength