Acetaminophen and Impaired Musculoskeletal Adaptations to Exercise Training

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Completed
• CT.gov ID: NCT01083901
• Collaborator: National Institute on Aging (NIA) (NIH)
• Enrollment: 34
• Location: 1
• Arms: 3
• Duration (Months): 58
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if taking the pain reliever acetaminophen (ACET) interferes with some of the benefits of weight lifting on muscles and bone density in older men.

Condition or Disease	Intervention/Treatment	Phase
Sarcopenia; Osteoporosis; Aging	Behavioral: Resistance training	N/A

Detailed Description

The commonly used pain relievers acetaminophen and ibuprofen may impair musculoskeletal adaptations to progressive resistance exercise training by inhibiting exercise-induced muscle protein synthesis.

To test the hypothesis that acetaminophen and ibuprofen would diminish training-induced increases in fat-free mass, untrained men (n=26) aged ≥ 50 years participated in 16 weeks of high-intensity progressive resistance exercise training and bone-loading exercises and were randomly assigned to take ACET (1000 mg), ibuprofen (400 mg) or placebo 2 hours before each exercise session.

The primary outcome was the change in total body fat-free mass measured by dual-energy X-ray absorptiometry (DXA) at baseline and week 16. Our primary interest was in the comparison of the acetaminophen and placebo groups.

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Official Title: Acetaminophen and Impaired Musculoskeletal Adaptations to Exercise Training
• Study Start Date: May 1, 2006
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Resistance training with Acetaminophen Acetaminophen	Behavioral: Resistance training; high intensity progressive resistance exercise training
Experimental: Resistance Training with ibuprofen Ibuprofen	Behavioral: Resistance training; high intensity progressive resistance exercise training
Placebo Comparator: placebo Placebo	Behavioral: Resistance training; high intensity progressive resistance exercise training

Outcome Measures

Primary Outcome Measures

1. Change in Total Body Fat-free Mass [16 weeks]

   change from baseline to 16 weeks in fat-free mass measured by DXA (Hologic Discovery W, version 12.6)

Secondary Outcome Measures

1. Change in Total Body Fat Mass [16 weeks]

   Change from baseline to 16 weeks in total body fat mass.

2. Changes in Upper Body Strength. [16 weeks]

   Strength was measured using the one-repetition maximum method. Upper body strength was a composite of bench press, overhead press, seated row, and lateral pull-down strength.

3. Change in Lower Body Strength [16 weeks]

   Strength was measured using the one-repetition maximum method. Lower body strength was a composite of knee flexion, knee extension, and leg press strength.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• average use of acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) [including aspirin] less than 3 days per month

• not currently engaged in moderate-to-vigorous weight-lifting exercise

• non-smoker

• willing to participate in a supervised exercise program for 9 months

Exclusion Criteria:

• relative or absolute contraindications to regular use of acetaminophen or NSAIDs including known allergy or intolerance to either drug,history of peptic ulcer or GI bleeding, anemia, asthma with bronchospasm induced by aspirin or other NSAIDS, moderate or severe renal impairment, known hepatobiliary disease

• contraindications to exercise testing and training including congestive heart failure class III or IV, uncontrolled hypertension and unstable cardiovascular disease

• thyroid dysfunction

• orthopedic problems that limit the ability to perform vigorous exercise or increase the likelihood of the use of pain medications

• drugs known to alter bone metabolism

• allergy to lidocaine

• diabetes mellitus requiring pharmacologic therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Denver	Aurora	Colorado	United States	80045

Sponsors and Collaborators

• University of Colorado, Denver
• National Institute on Aging (NIA)

Investigators

• Principal Investigator: Catherine Jankowski, PhD, University of Colorado, Denver

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT01083901
• Other Study ID Numbers: 06-0343; R21AG027809
• First Posted: Mar 10, 2010
• Last Update Posted: Jun 24, 2013
• Last Verified: Jun 1, 2013

• Additional relevant MeSH terms: Osteoporosis; Sarcopenia

Study Results

Participant Flow

Recruitment Details	Participants were enrolled from Dec 2006 to Jan 2010. They were recruited from the greater Denver area using advertisements.
Pre-assignment Detail	Volunteers who did not meet inclusion criteria were excluded from the study during the initial screening visits prior to randomization to the study arms.

Arm/Group Title	Acetaminophen and Resistance Exercise	Ibuprofen and Resistance Exercise	Placebo and Resistance Exercise
Arm/Group Description	Progressive resistance exercise training and bone-loading exercise on up to 6 days per week and administration of acetaminophen, 1000 mg, taken 2 hours before exercise on exercise days for up to 36 weeks.	Progressive resistance exercise training and bone-loading exercise on up to 6 days per week and administration of acetaminophen, 400 mg, taken 2 hours before exercise on exercise days for up to 36 weeks.	Progressive resistance exercise training and bone-loading exercise on up to 6 days per week and placebo pills (matching active study drug) taken 2 hours before exercise on exercise days for up to 36 weeks.
Period Title: Overall Study
STARTED	13	8	13
COMPLETED	12	6	11
NOT COMPLETED	1	2	2

Baseline Characteristics

Arm/Group Title	Acetaminophen and Resistance Exercise	Ibuprofen and Resistance Exercise	Placebo and Resistance Exercise	Total
Arm/Group Description	Progressive resistance exercise training and bone-loading exercise on up to 6 days per week and administration of acetaminophen, 1000 mg, taken 2 hours before exercise on exercise days for up to 36 weeks.	Progressive resistance exercise training and bone-loading exercise on up to 6 days per week and administration of acetaminophen, 400 mg, taken 2 hours before exercise on exercise days for up to 36 weeks.	Progressive resistance exercise training and bone-loading exercise on up to 6 days per week and placebo pills (matching active study drug) taken 2 hours before exercise on exercise days for up to 36 weeks.	Total of all reporting groups
Overall Participants	13	8	13	34
Age (years) [Mean (Standard Deviation) ]
United States	63 (5)	58 (6)	62 (7)	61 (6)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	13 100%	8 100%	13 100%	34 100%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	181 (8)	178 (10)	176 (7)	178 (6.4)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	94.5 (16.6)	89.3 (12.5)	87.9 (18.0)	90.4 (16.4)
Fat-free mass (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	65.2 (6.1)	63.5 (8.2)	62.7 (9.1)	63.4 (8.0)
Fat mass (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	29.3 (12.6)	25.8 (5.3)	25.2 (9.6)	27.0 (10.0)

Outcome Measures

1. Primary Outcome

Title	Change in Total Body Fat-free Mass
Description	change from baseline to 16 weeks in fat-free mass measured by DXA (Hologic Discovery W, version 12.6)
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

All participants with baseline and 16 week data were included in the analysis (i.e., intention-to-treat).

Arm/Group Title	Acetaminophen and Resistance Exercise Training	Ibuprofen and Resistance Exercise Training	Placebo and Resistance Exercise Training
Arm/Group Description
Measure Participants	12	6	11
Mean (Standard Error) [kg]	1.5 (0.6)	2.3 (0.9)	0.7 (0.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Acetaminophen and Resistance Exercise Training, Ibuprofen and Resistance Exercise Training, Placebo and Resistance Exercise Training
	Comments	The null hypothesis was that the changes in total body fat-free mass in response to resistance exercise training would not be different among the groups. The expected difference in fat-free mass between the Acetaminophen and Placebo groups was 1.8 +/- 1.0% with a 3.6 +/1 1.0% increase in fat-free mass in the Placebo group. The study was designed to achieve 96% power at the 0.05 level with 10 men in the acetaminophen and placebo groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.38
	Comments
	Method	ANCOVA
	Comments	Changes from baseline to 16 weeks were regressed on the baseline measurement.

2. Secondary Outcome

Title	Change in Total Body Fat Mass
Description	Change from baseline to 16 weeks in total body fat mass.
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Acetaminophen and Resistance Exercise Training	Ibuprofen and Resistance Exercise Training	Placebo and Resistance Exercise Training
Arm/Group Description
Measure Participants	12	6	11
Mean (Standard Error) [kg]	-1.5 (0.6)	-1.4 (0.9)	-0.2 (0.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Acetaminophen and Resistance Exercise Training, Ibuprofen and Resistance Exercise Training, Placebo and Resistance Exercise Training
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.23
	Comments
	Method	ANCOVA
	Comments	The change in fat mass was regressed on the baseline measure.

3. Secondary Outcome

Title	Changes in Upper Body Strength.
Description	Strength was measured using the one-repetition maximum method. Upper body strength was a composite of bench press, overhead press, seated row, and lateral pull-down strength.
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Acetaminophen and Resistance Exercise Training	Ibuprofen and Resistance Exercise Training	Placebo and Resistance Exercise Training
Arm/Group Description
Measure Participants	12	6	11
Mean (Standard Error) [lbs]	19.5 (5.5)	35.2 (8.6)	26.5 (5.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Acetaminophen and Resistance Exercise Training, Ibuprofen and Resistance Exercise Training, Placebo and Resistance Exercise Training
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments
	Method	ANCOVA
	Comments	Change in strength was regressed on baseline measures.

4. Secondary Outcome

Title	Change in Lower Body Strength
Description	Strength was measured using the one-repetition maximum method. Lower body strength was a composite of knee flexion, knee extension, and leg press strength.
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Acetaminophen and Resistance Exercise Training	Ibuprofen and Resistance Exercise Training	Placebo and Resistance Exercise Training
Arm/Group Description
Measure Participants	12	6	11
Mean (Standard Error) [lbs]	33.1 (9.4)	40.8 (14.6)	18.0 (9.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Acetaminophen and Resistance Exercise Training, Ibuprofen and Resistance Exercise Training, Placebo and Resistance Exercise Training
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.37
	Comments
	Method	ANCOVA
	Comments	Changes in strength were regressed on the baseline measure.

Adverse Events

Time Frame	Throughout the study.
Arm/Group Title	Acetaminophen and Resistance Exercise Training		Ibuprofen and Resistance Exercise Traininig		Placebo and Resistance Exercise Training
Arm/Group Description
All Cause Mortality
	Acetaminophen and Resistance Exercise Training		Ibuprofen and Resistance Exercise Traininig		Placebo and Resistance Exercise Training
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Acetaminophen and Resistance Exercise Training		Ibuprofen and Resistance Exercise Traininig		Placebo and Resistance Exercise Training
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/8 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Acetaminophen and Resistance Exercise Training		Ibuprofen and Resistance Exercise Traininig		Placebo and Resistance Exercise Training
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/8 (0%)		0/13 (0%)

Limitations/Caveats

This was a preliminary study that was limited by small sample size, exclusion of women, and the duration of intervention which was too brief to measure changes in bone mineral density.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.