Exercise And Rosuvastatin Treatment: Is There an Anti-Inflammatory Synergy?

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2007 by Purdue University.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
Purdue University
ClinicalTrials.gov Identifier:
NCT00295373
First received: February 21, 2006
Last updated: April 19, 2007
Last verified: April 2007
  Purpose

The purpose of this study is to determine whether the effects of rosuvastatin treatment and exercise training can be synergistic, with respect to the innate immune receptor TLR4, markers of systemic inflammation, and stimulated production of inflammatory cytokines, in hypercholesterolemic subjects. It is hypothesized that a rosuvastatin and exercise intervention will synergistically lower measured variables, so as to be anti-inflammatory.


Condition Intervention Phase
Nonfamilial Hypercholesterolemia
Physical Inactivity
Drug: Rosuvastatin
Behavioral: Exercise Training
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 4 Clinical Trial to Examine the Role of Rosuvastatin and Exercise Treatment in Modulating Inflammatory Response in Hypercholesterolemic Subjects

Resource links provided by NLM:


Further study details as provided by Purdue University:

Primary Outcome Measures:
  • The following measures will be made at 0, 10 and 20 weeks:
  • Monocyte cell-surface expression of TLR4, CD14, and CD16
  • LPS-stimulated whole blood production of IL-6 and TNF-α
  • Serum levels of hsCRP and TNF-α
  • Serum levels of Endotoxin LDL, OxLDL, HDL, sCD14, and
  • Lipopolysaccharide Binding Protein.

Secondary Outcome Measures:
  • Creatine kinase & ALT (0, 5, 10 weeks; rosuvastatin group)
  • Creatine kinase & ALT (48hrs after 1st and 5th exercise
  • bout; rosuvastatin + exercise group)

Estimated Enrollment: 48
Study Start Date: February 2006
Estimated Study Completion Date: August 2007
Detailed Description:

Both statin drugs and exercise training are known to exert anti-inflammatory effects. We found that both high levels of physical activity and an exercise training program reduced markers of inflammation and lowered monocyte Toll-like receptor 4 (TLR4) expression. It has not been determined whether statins exert their anti-inflammatory effects through the toll-like receptors or whether combined statin/exercise treatment will exert synergistic anti-inflammatory effects. Thus, the primary purposes of this study are two-fold: 1) Determine whether rosuvastatin treatment downregulates LPS-induced inflammatory responses, serum hsCRP, and monocyte TLR4 expression in hypercholesterolemic patients; and 2) Determine whether adding exercise training to rosuvastatin treatment induces an anti-inflammatory synergy and further lowers LPS-induced inflammatory response, hsCRP, and TLR4 expression. Thirty two hypercholesterolemic (total cholesterol > 200 mg/dL, LDL > 130 mg/dL) will be randomly divided into two groups: statin (ST) and statin and exercise (ST+E). Sixteen physically active, no-statin subjects will also be recruited as a control group(CON). After baseline blood sampling, ST and ST+E groups will begin a 10-week course of rosuvastatin calcium treatment (10 mg/d) after which a second blood sample will be obtained. The ST+E group will then begin a 10 week (three days per week) combined endurance (20 min at 70% of heart rate reserve) and resistive training (2 sets of 10 upper- and lower-body exercises) program. The ST group will not exercise and both ST+E and ST groups will continue taking their medication, as prescribed. A final blood sample will be taken at the end of this 10-week segment. Blood samples will also be taken from the CON group at 0, 10 and 20 weeks. Monocyte expression of TLR4, CD14 (LPS receptor) and CD16 (monocyte maturation marker) will be assessed using flow cytometry. LPS-stimulated inflammatory cytokine production and serum levels of hsCRP, TNF-a, oxLDL, LDL, HDL, endotoxin, LPS binding protein, and sCD14 will also be measured at each time point (baseline, 10 weeks, 20 weeks). These experiments will allow us to determine whether rosuvastatin downregulates TLR4, an important mediator of inflammation, and whether exercise, known to lower TLR4 expression, can augment the rosuvastatin effects. Regular exercise and statin treatment are known to reduce disease risk, but the benefits of these treatments is infrequently attributed to their anti-inflammatory effects. It is important to document mechanisms of anti-inflammatory action for exercise training and statin treatment and to determining whether these treatments have combined beneficial effects.

  Eligibility

Ages Eligible for Study:   40 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Nonfamilial hypercholesterolemia
  • Total cholesterol >200 mg/dl, LDL >130 mg/dL
  • Physical inactivity
  • Moderate to low alcohol intake

Exclusion Criteria:

  • Liver or kidney disease
  • Acute illness or infection
  • Use of corticosteroids, ACE inhibitors, platelet aggregating inhibitors, thiazolidinediones, and bis-phosphonates.
  • Use of cyclosporine, warfarin, gemfibrozil or other lipid lowering agents
  • Regular antacid or aspirin use
  • Type I & II diabetes with insulin treatment
  • hypothyroidism, and/or renal insufficiency
  • Chronic/debilitating osteoarthritis
  • Rheumatoid arthritis
  • Central or peripheral nervous system disorders
  • Anti-depressant medications
  • Major affective disorder
  • HIV infection or auto-immune disorders
  • Use of tobacco products
  • unexplained or intended weight loss of > 2 kg during the previous six months
  • Surgery within the previous three months
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00295373

Locations
United States, Indiana
Purdue University
West Lafayette, Indiana, United States, 47906
Sponsors and Collaborators
Purdue University
Investigators
Principal Investigator: Robert E Hannemann, MD Purdue University
Study Director: Michael G Flynn, PhD Purdue University
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00295373     History of Changes
Other Study ID Numbers: 0HQ01, IRB Protocol Ref.#: 0504001888
Study First Received: February 21, 2006
Last Updated: April 19, 2007
Health Authority: United States: Institutional Review Board

Keywords provided by Purdue University:
Hypercholesterolemia
Exercise
Statin
Rosuvastatin
TLR4
Inflammation

Additional relevant MeSH terms:
Hypercholesterolemia
Dyslipidemias
Hyperlipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Rosuvastatin
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014