Aging, Physical Fitness
Conditions
Keywords
body composition, bone density, cyclooxygenase inhibitor, bone metabolism, muscle function, muscle strength
Brief summary
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
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.
Interventions
DRUGIbuprofen
400 mg with each exercise session (up to 5 days per week) for 9 months
DRUGPlacebo
with each exercise session (up to 5 days per week) for 9 months
BEHAVIORALmusculoskeletal-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
Sponsors
National Institute on Aging (NIA)
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to 75 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| Change in Thigh Cross-sectional Muscle Area | Baseline and after 9 months of training |
| Percentage Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at 9 Months | Baseline and after 9 months of training |
| Expression of Selected Proteins and Genes Associated With Muscle Build-up and Breakdown | Baseline and after 9 months of training |
| Bone Turnover Markers | Baseline, and after 4.5 & 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 37 |
| 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 | 51 |
| 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 | 42 |
| Total | 130 |
Baseline characteristics
| Characteristic | Placebo Pre and Post Exercise | Total | Placebo Pre and Ibuprofen Post Exercise | Ibuprofen Pre and Placebo Post Exercise |
|---|---|---|---|---|
| Age, Continuous | 64 years STANDARD_DEVIATION 4 | 64 years STANDARD_DEVIATION 4 | 66 years STANDARD_DEVIATION 4 | 64 years STANDARD_DEVIATION 4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 5 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants | 125 Participants | 41 Participants | 49 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 7 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 3 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 33 Participants | 115 Participants | 35 Participants | 47 Participants |
| Region of Enrollment United States | 37 participants | 130 participants | 42 participants | 51 participants |
| Sex: Female, Male Female | 23 Participants | 82 Participants | 27 Participants | 32 Participants |
| Sex: Female, Male Male | 14 Participants | 48 Participants | 15 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 37 | 1 / 51 | 0 / 42 |
| serious Total, serious adverse events | 0 / 37 | 0 / 51 | 0 / 42 |
Outcome results
Primary
Change From Baseline in Fat-free Mass at 9 Months
Time frame: Baseline and after 9 months of training
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Pre and Post Exercise | Change From Baseline in Fat-free Mass at 9 Months | 0.6 change in kg | Standard Deviation 1.1 |
| Ibuprofen Pre and Placebo Post Exercise | Change From Baseline in Fat-free Mass at 9 Months | 0.4 change in kg | Standard Deviation 1.6 |
| Placebo Pre and Ibuprofen Post Exercise | Change From Baseline in Fat-free Mass at 9 Months | 0.6 change in kg | Standard Deviation 1.4 |
Primary
Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 9 Months
Time frame: Baseline and after 9 months of training
Population: One participant in the Ibuprofen pre and placebo post exercise group had an uninterpretable spine scan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Pre and Post Exercise | Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 9 Months | 1.3 Percentage change in lumbar spine BMD | Standard Deviation 2.8 |
| Ibuprofen Pre and Placebo Post Exercise | Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 9 Months | 1.5 Percentage change in lumbar spine BMD | Standard Deviation 2.5 |
| Placebo Pre and Ibuprofen Post Exercise | Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 9 Months | 0.9 Percentage change in lumbar spine BMD | Standard Deviation 2.2 |
Primary
Percentage Change From Baseline in Total Hip Bone Mineral Density (BMD) at 9 Months
Time frame: Baseline and after 9 months of training
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Pre and Post Exercise | Percentage Change From Baseline in Total Hip Bone Mineral Density (BMD) at 9 Months | 0.5 percentage change in total hip BMD | Standard Deviation 2.6 |
| Ibuprofen Pre and Placebo Post Exercise | Percentage Change From Baseline in Total Hip Bone Mineral Density (BMD) at 9 Months | 0.0 percentage change in total hip BMD | Standard Deviation 1.9 |
| Placebo Pre and Ibuprofen Post Exercise | Percentage Change From Baseline in Total Hip Bone Mineral Density (BMD) at 9 Months | -0.3 percentage change in total hip BMD | Standard Deviation 2 |
Secondary
Bone Turnover Markers
Time frame: Baseline, and after 4.5 & 9 months of training
Population: 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).
Secondary
Change in Thigh Cross-sectional Muscle Area
Time frame: Baseline and after 9 months of training
Population: 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).
Secondary
Expression of Selected Proteins and Genes Associated With Muscle Build-up and Breakdown
Time frame: Baseline and after 9 months of training
Population: 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).
Secondary
Percentage Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at 9 Months
Time frame: Baseline and after 9 months of training
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Pre and Post Exercise | Percentage Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at 9 Months | 0.2 percentage change in BMD | Standard Deviation 2.9 |
| Ibuprofen Pre and Placebo Post Exercise | Percentage Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at 9 Months | 0.2 percentage change in BMD | Standard Deviation 2.8 |
| Placebo Pre and Ibuprofen Post Exercise | Percentage Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at 9 Months | -0.1 percentage change in BMD | Standard Deviation 2.1 |
Secondary
Percentage Change From Baseline in Sub-trochanter Bone Mineral Density (BMD) at 9 Months
Time frame: Baseline and after 9 months of training
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Pre and Post Exercise | Percentage Change From Baseline in Sub-trochanter Bone Mineral Density (BMD) at 9 Months | 0.5 percentage change in BMD | Standard Deviation 3.4 |
| Ibuprofen Pre and Placebo Post Exercise | Percentage Change From Baseline in Sub-trochanter Bone Mineral Density (BMD) at 9 Months | 0.0 percentage change in BMD | Standard Deviation 2.3 |
| Placebo Pre and Ibuprofen Post Exercise | Percentage Change From Baseline in Sub-trochanter Bone Mineral Density (BMD) at 9 Months | -0.3 percentage change in BMD | Standard Deviation 2.5 |
Secondary
Percentage Change From Baseline in Trochanter Bone Mineral Density (BMD) at 9 Months
Time frame: Baseline and after 9 months of training
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Pre and Post Exercise | Percentage Change From Baseline in Trochanter Bone Mineral Density (BMD) at 9 Months | 1.1 percentage change in BMD | Standard Deviation 3.1 |
| Ibuprofen Pre and Placebo Post Exercise | Percentage Change From Baseline in Trochanter Bone Mineral Density (BMD) at 9 Months | 0.0 percentage change in BMD | Standard Deviation 2.3 |
| Placebo Pre and Ibuprofen Post Exercise | Percentage Change From Baseline in Trochanter Bone Mineral Density (BMD) at 9 Months | -0.1 percentage change in BMD | Standard Deviation 2.7 |