This trial is active, not recruiting.

Conditions nonfamilial hypercholesterolemia, physical inactivity
Treatments rosuvastatin, exercise training
Phase phase 4
Sponsor Purdue University
Start date February 2006
End date August 2007
Trial size 48 participants
Trial identifier NCT00295373, 0HQ01, IRB Protocol Ref.#: 0504001888


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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model factorial assignment
Masking open label
Primary purpose treatment

Primary Outcomes

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

Secondary Outcomes

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

Eligibility Criteria

Male or female participants from 40 years up to 65 years old.

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

Additional Information

Official title Phase 4 Clinical Trial to Examine the Role of Rosuvastatin and Exercise Treatment in Modulating Inflammatory Response in Hypercholesterolemic Subjects
Principal investigator Robert E Hannemann, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in April 2007.
Information provided to ClinicalTrials.gov by Purdue University.