Myogenic and Osteogenic Responses to eXercise and Ibuprofen (MOXI)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT00462722
First received: April 17, 2007
Last updated: June 18, 2013
Last verified: June 2013
  Purpose

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


Condition Intervention
Aging
Physical Fitness
Drug: Ibuprofen
Drug: Placebo
Behavioral: musculoskeletal-loading exercise

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Official Title: COX Inhibition & Musculoskeletal Responses to Exercise

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Changes in lumbar spine bone mineral density (BMD) [ Time Frame: Baseline, and after 4.5 & 9 months of training ] [ Designated as safety issue: No ]
  • total hip BMD [ Time Frame: Baseline, and after 4.5 & 9 months of training ] [ Designated as safety issue: No ]
  • fat-free mass [ Time Frame: Baseline, and after 4.5 & 9 months of training ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in BMD at other sites [ Time Frame: Baseline, and after 4.5 & 9 months of training ] [ Designated as safety issue: No ]
  • thigh cross-sectional muscle area [ Time Frame: Baseline and after 9 months of training ] [ Designated as safety issue: No ]
  • bone turnover markers [ Time Frame: Baseline, and after 4.5 & 9 months of training ] [ Designated as safety issue: No ]
  • Expression of selected proteins and genes associated with muscle build-up and breakdown [ Time Frame: Baseline and after 9 months of training ] [ Designated as safety issue: No ]

Enrollment: 189
Study Start Date: July 2007
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo pre and post exercise
placebo before and after musculoskeletal-loading exercise
Drug: Placebo
with each exercise session (up to 5 days per week) for 9 months
Behavioral: 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
Experimental: Placebo pre and ibuprofen post exercise
placebo before and ibuprofen after musculoskeletal-loading exercise
Drug: Ibuprofen
400 mg with each exercise session (up to 5 days per week) for 9 months
Other Names:
  • Motrin
  • Advil
Drug: Placebo
with each exercise session (up to 5 days per week) for 9 months
Behavioral: 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
Experimental: Ibuprofen pre and placebo post exercise
ibuprofen before and placebo after musculoskeletal-loading exercise
Drug: Ibuprofen
400 mg with each exercise session (up to 5 days per week) for 9 months
Other Names:
  • Motrin
  • Advil
Drug: Placebo
with each exercise session (up to 5 days per week) for 9 months
Behavioral: 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

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.

  Eligibility

Ages Eligible for Study:   60 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  • PPI(Proton Pump Inhibitor) 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00462722

Locations
United States, Colorado
University of Colorado Denver
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
Investigators
Principal Investigator: Wendy Kohrt, PhD University of Colorado, Denver
  More Information

Additional Information:
Publications:
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT00462722     History of Changes
Other Study ID Numbers: 06-0769, R01AG018857
Study First Received: April 17, 2007
Last Updated: June 18, 2013
Health Authority: United States: Federal Government

Keywords provided by University of Colorado, Denver:
body composition
bone density
cyclooxygenase inhibitor
bone metabolism
muscle function
muscle strength

Additional relevant MeSH terms:
Ibuprofen
Cyclooxygenase Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents

ClinicalTrials.gov processed this record on April 23, 2014