Myogenic and Osteogenic Responses to eXercise and Ibuprofen - Full Text View

Sponsor:	National Institute on Aging (NIA)
Information provided by:	National Institute on Aging (NIA)
ClinicalTrials.gov Identifier:	NCT00462722

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:	Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment
Official Title:	COX Inhibition & Musculoskeletal Responses to Exercise

Resource links provided by NLM:

MedlinePlus related topics: Exercise and Physical Fitness

Drug Information available for: Ibuprofen

U.S. FDA Resources

Further study details as provided by National Institute on Aging (NIA):

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 ]

Estimated Enrollment:	180
Study Start Date:	July 2007
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Placebo Comparator placebo before and after 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
2: Experimental placebo before and ibuprofen after exercise	Drug: Ibuprofen 400 mg with each exercise session (up to 5 days per week) for 9 months 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
3: Experimental ibuprofen before and placebo after exercise	Drug: Ibuprofen 400 mg with each exercise session (up to 5 days per week) for 9 months 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, testosterone, bisphosphonates, teriparatide, calcitonin, GnRH 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

Contacts

Contact: Marsha Steirn, MBA, DTR

720-848-6461

marsha.steirn@ucdenver.edu

Locations

United States, Colorado
University of Colorado Denver	Recruiting
Aurora, Colorado, United States, 80045
Principal Investigator: Wendy Kohrt, PhD
Sub-Investigator: Daniel Barry, MD
Sub-Investigator: Wendolyn Gozansky, MD, MPH
Sub-Investigator: Catherine Jankowski, PhD

Sponsors and Collaborators

National Institute on Aging (NIA)

Investigators

Principal Investigator:

Wendy Kohrt, PhD

University of Colorado, Denver

More Information

Publications:

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.

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. Epub 2002 Mar 26.

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.

Responsible Party:	University of Colorado Denver ( Wendy Kohrt, PhD )
Study ID Numbers:	AG0080, AG018857
Study First Received:	April 17, 2007
Last Updated:	December 4, 2009
ClinicalTrials.gov Identifier:	NCT00462722 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institute on Aging (NIA):

body composition
bone density
cyclooxygenase inhibitor

bone metabolism
muscle function
muscle strength

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Ibuprofen
Molecular Mechanisms of Pharmacological Action
Cyclooxygenase Inhibitors
Physiological Effects of Drugs
Enzyme Inhibitors
Pharmacologic Actions
Analgesics, Non-Narcotic

Sensory System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on February 08, 2010