Systemic Immunomodulatory Effects and Pharmacogenetics of Atorvastatin in Early Atherosclerosis

• Sponsor: University of Florida (Other)
• Overall Status: Completed
• CT.gov ID: NCT00361283
• Collaborator: American Heart Association (Other), American College of Clinical Pharmacy (Other)
• Enrollment: 108
• Location: 1
• Arm: 1
• Duration (Months): 55
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

The purpose of the study is to test whether atorvastatin (also known as Lipitor) has anti-inflammatory effects in people with no known heart disease or high cholesterol. We also are investigating whether or not genetic differences between people plays a role in the drug response.

Condition or Disease	Intervention/Treatment	Phase
Inflammation	Drug: Atorvastatin	Phase 4

Detailed Description

All subjects received 16 weeks of Atorvastatin after a two week run in. Key dependent variables were the 16 week value minus the baseline value (post run-in). Last observation carried forward was used for missing values. The key comparisons are for two groups OATP1B1 reduced carriers and on-carriers and their association with Cytokines and Lipids. Secondarily, we were interested in changes over the 16 weeks for the pooled sample, irrespective of genetics.

Study Design

• Study Type: Interventional
• Actual Enrollment: 108 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Screening
• Official Title: Systemic Immunomodulatory Effects and Pharmacogenetics of Atorvastatin in Early Atherosclerosis
• Study Start Date: Jun 1, 2004
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Jan 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Other: atorvastatin 80mg of atorvastatin given once daily for 16 weeks	Drug: Atorvastatin; atorvastatin 80mg tablets given by mouth once daily for 16 weeks with follow-up visits every 4 weeks; Other Names: Lipitor

Outcome Measures

Primary Outcome Measures

1. Mean Change in Level: Week 16-baseline in Ena-78 [16 weeks after baseline]

   We take difference week 16 minus week 0 for ENA-78 and use a one sample t comparison.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• 18+ years old

• Normocholesterolemic

Exclusion Criteria:

• Cardiovascular disease or risk equivalents

• Malignancy

• Active alcohol abuse

• Contraindications to statins

• Interacting drugs

• Chronic anti-inflammatory drugs

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Florida	Gainesville	Florida	United States	32610

Sponsors and Collaborators

• University of Florida
• American Heart Association
• American College of Clinical Pharmacy

Investigators

• Principal Investigator: Reginald Frye, PharmD, PhD, University of Florida College of Pharmacy

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT00361283
• Other Study ID Numbers: 0435278B
• First Posted: Aug 8, 2006
• Last Update Posted: May 15, 2012
• Last Verified: Apr 1, 2012

• Additional relevant MeSH terms: Atherosclerosis; Inflammation; Atorvastatin

Study Results

Participant Flow

Recruitment Details	University of Florida Clinical Research Center. Study started June 2004 and ended January 9, 2009.

Arm/Group Title	Atorvastatin
Arm/Group Description	80mg of atorvastatin given once daily for 16 weeks
Period Title: Overall Study
STARTED	108
COMPLETED	81
NOT COMPLETED	27

Baseline Characteristics

Arm/Group Title	Atorvastatin
Arm/Group Description	80mg of atorvastatin given once daily for 16 weeks
Overall Participants	108
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	107 99.1%
>=65 years	1 0.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	31.6 (12.6)
Sex: Female, Male (Count of Participants)
Female	66 61.1%
Male	42 38.9%
Region of Enrollment (participants) [Number]
United States	108 100%

Outcome Measures

1. Primary Outcome

Title	Mean Change in Level: Week 16-baseline in Ena-78
Description	We take difference week 16 minus week 0 for ENA-78 and use a one sample t comparison.
Time Frame	16 weeks after baseline

Outcome Measure Data

Analysis Population Description

Power calculation

Arm/Group Title	Atorvastatin 80 MG/Day
Arm/Group Description	Atorvastatin 80 MG/day
Measure Participants	81
Mean (Standard Deviation) [pg/ml]	-111.2 (690.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atorvastatin 80 MG/Day
	Comments	The study in healthy volunteers was to compare levels at baseline to 16 weeks in ENA-78, a cytokine. The one sample t-test was used to obtain the result.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.15
	Comments	No confounders were controlled for as each person is his/her own control.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-111
	Confidence Interval	(2-Sided) 95%; -264 to 42
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 76.7
	Estimation Comments

Adverse Events

Time Frame	16 weeks
Arm/Group Title	Atorvastatin
Arm/Group Description	80mg of atorvastatin given once daily for 16 weeks
All Cause Mortality
	Atorvastatin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Atorvastatin
	Affected / at Risk (%)	# Events
Total	0/108 (0%)
Other (Not Including Serious) Adverse Events
	Atorvastatin
	Affected / at Risk (%)	# Events
Total	14/108 (13%)
General disorders
Headache	12/108 (11.1%)	12
Musculoskeletal and connective tissue disorders
Muscle aches	14/108 (13%)	14

Limitations/Caveats

[Not Specified]

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.