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| ID | Type | Description | Link |
|---|---|---|---|
| R01AG018857 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo pre and post exercise | Placebo Comparator | placebo before and after musculoskeletal-loading exercise |
|
| Placebo pre and ibuprofen post exercise | Experimental | placebo before and ibuprofen after musculoskeletal-loading exercise |
|
| Ibuprofen pre and placebo post exercise | Experimental | ibuprofen before and placebo after musculoskeletal-loading exercise |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ibuprofen | Drug | 400 mg with each exercise session (up to 5 days per week) for 9 months |
|
| 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 |
| 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 |
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Inclusion Criteria:
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
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| Name | Affiliation | Role |
|---|---|---|
| Wendy Kohrt, PhD | University of Colorado, Denver | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Colorado Denver | Aurora | Colorado | 80045 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 8074209 | Background | Chow JW, Chambers TJ. Indomethacin has distinct early and late actions on bone formation induced by mechanical stimulation. Am J Physiol. 1994 Aug;267(2 Pt 1):E287-92. doi: 10.1152/ajpendo.1994.267.2.E287. | |
| 12004337 | Background | Li J, Burr DB, Turner CH. Suppression of prostaglandin synthesis with NS-398 has different effects on endocortical and periosteal bone formation induced by mechanical loading. Calcif Tissue Int. 2002 Apr;70(4):320-9. doi: 10.1007/s00223-001-1025-y. Epub 2002 Mar 26. |
| Label | URL |
|---|---|
| Data analysis plan MOXI Study | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo Pre and Post Exercise | placebo before and after musculoskeletal-loading exercise Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: 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 |
| FG001 | Ibuprofen Pre and Placebo Post Exercise | ibuprofen before and placebo after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: 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 |
| FG002 | Placebo Pre and Ibuprofen Post Exercise | placebo before and ibuprofen after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo Pre and Post Exercise | placebo before and after musculoskeletal-loading exercise Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 9 Months | One participant in the "Ibuprofen pre and placebo post exercise" group had an uninterpretable spine scan. | Posted | Mean | Standard Deviation | Percentage change in lumbar spine BMD | Baseline and after 9 months of training |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo Pre and Post Exercise | placebo before and after musculoskeletal-loading exercise Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: 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 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| change in estimated glomerular filtration rate (eGFR) | Renal and urinary disorders | Systematic Assessment | Decrease in eGFR > 25% triggered discontinuation of study drug |
The study did not include a no-exercise control group. The variability in the BMD responses was greater than expected.
The results may be specific to ibuprofen and not to other NSAIDs.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Catherine Jankowski | University of Colorado Anschutz Medical Campus | 303-724-7383 | catherine.jankowski@ucdenver.edu |
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| ID | Term |
|---|---|
| D007052 | Ibuprofen |
| ID | Term |
|---|---|
| D010666 | Phenylpropionates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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|
| Placebo | Drug | with each exercise session (up to 5 days per week) for 9 months |
|
| musculoskeletal-loading exercise | Behavioral | 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 |
|
| 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 |
| 11832356 | Background | Trappe TA, White F, Lambert CP, Cesar D, Hellerstein M, Evans WJ. Effect of ibuprofen and acetaminophen on postexercise muscle protein synthesis. Am J Physiol Endocrinol Metab. 2002 Mar;282(3):E551-6. doi: 10.1152/ajpendo.00352.2001. |
| 33876259 | Derived | 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. |
| BG001 | Ibuprofen Pre and Placebo Post Exercise | ibuprofen before and placebo after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: 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 |
| BG002 | Placebo Pre and Ibuprofen Post Exercise | placebo before and ibuprofen after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: 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 |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
ibuprofen before and placebo after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: 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 |
| OG002 | Placebo Pre and Ibuprofen Post Exercise | placebo before and ibuprofen after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: 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 |
|
|
| Primary | Percentage Change From Baseline in Total Hip Bone Mineral Density (BMD) at 9 Months | One participant in the "Placebo pre and post exercise" group and two participants in the "Ibuprofen pre and placebo post exercise" group had uninterpretable hip scans. | Posted | Mean | Standard Deviation | percentage change in total hip BMD | Baseline and after 9 months of training |
|
|
|
| Primary | Change From Baseline in Fat-free Mass at 9 Months | Posted | Mean | Standard Deviation | change in kg | Baseline and after 9 months of training |
|
|
|
| Secondary | Percentage Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at 9 Months | One participant in the "Placebo pre and post exercise" group and two participants in the "Ibuprofen pre and placebo post exercise" group had uninterpretable spine scans. | Posted | Mean | Standard Deviation | percentage change in BMD | Baseline and after 9 months of training |
|
|
|
| Secondary | Percentage Change From Baseline in Trochanter Bone Mineral Density (BMD) at 9 Months | Posted | Mean | Standard Deviation | percentage change in BMD | Baseline and after 9 months of training |
|
|
|
| Secondary | Percentage Change From Baseline in Sub-trochanter Bone Mineral Density (BMD) at 9 Months | One participant in the "Placebo pre and post exercise" group and two participants in the "Ibuprofen pre and placebo post exercise" groups had uninterpretable hip scans. | Posted | Mean | Standard Deviation | percentage change in BMD | Baseline and after 9 months of training |
|
|
|
| Secondary | Change in Thigh Cross-sectional Muscle Area | Because of the costs associated with data analysis for this secondary outcome, we did not pursue the analysis after learning the results of the primary outcome (fat-free mass). | Posted | Baseline and after 9 months of training |
|
|
| Secondary | Bone Turnover Markers | Because of the costs associated with the assays and data analysis of bone turnover markers, we did not pursue data collection after learning of the primary outcomes (changes in BMD). | Posted | Baseline, and after 4.5 & 9 months of training |
|
|
| Secondary | Expression of Selected Proteins and Genes Associated With Muscle Build-up and Breakdown | Because of the costs associated with gene and protein expression techniques and data reduction, we did not pursue this secondary outcome after learning the results of the primary outcome (change in fat-free mass). | Posted | Baseline and after 9 months of training |
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|
| 0 |
| 37 |
| 0 |
| 37 |
| EG001 | Ibuprofen Pre and Placebo Post Exercise | ibuprofen before and placebo after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: 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 | 0 | 51 | 1 | 51 |
| EG002 | Placebo Pre and Ibuprofen Post Exercise | placebo before and ibuprofen after musculoskeletal-loading exercise Ibuprofen: 400 mg with each exercise session (up to 5 days per week) for 9 months Placebo: with each exercise session (up to 5 days per week) for 9 months musculoskeletal-loading exercise: 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 | 0 | 42 | 0 | 42 |
|
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