NCT01732718
Trial name or title	The Effect of Atorvastatin on Endothelial Dysfunction and Albuminuria in Sickle Cell Disease (in the Grant Entitled: Endothelial Dysfunction in the Pathogenesis of Sickle Cell Nephropathy)
Methods	Phase 2 randomised cross-over assignment; double-blind (participant, care provider, investigator, outcomes assessor) trial
Participants	Inclusion criteria: Sickle cell anemia (HbSS) or sickle-betaº thalassemia (HbS-betaº thal) between ages of 18 and 60 years; albuminuria (micro- or macroalbuminuria, defined as =/> 30mg/g creatinine); serum ALT and/or GGT </= 2 times upper limits of normal; platelet count > 150,000 cu/mm; normal baseline coagulation profile (PT, INR, and PTT); non-crisis, steady state with no severe pain episodes during the preceding 4 weeks, and no documented infection in the 2 weeks prior to enrolment; ability to understand the requirements of the study; if a woman of childbearing potential, must use an adequate method of contraception; and if receiving hydroxyurea, ACE inhibitors or ARB), should be on a stable dose for at least 3 months. Exclusion criteria: hypersensitivity to any component of atorvastatin, or history of adverse reaction to statins; pregnant or breastfeeding; on statin therapy; history of metastatic cancer; current history of alcohol abuse; history of diabetes mellitus or poorly controlled systemic hypertension; end-stage renal disease; total cholesterol level < 80 mg/dL and LDL cholesterol > 130 mg/dL; on a chronic transfusion program; ingested any investigational drugs within the past 4 weeks; prior history of any myopathy; allergy to nitroglycerin; taking any of the following drugs: phosphodiesterase-5 inhibitors (e.g. sildenafil), cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitors (e.g. cyclosporine, protease inhibitors), macrolide antibiotics (e.g. clarithromycin, erythromycin), fibric acid derivatives (e.g. gemfibrozil), niacin, colchicines, antifungal agents (azole derivatives), amiodarone, danazol, daptomycin, diltiazem, verapamil, eltrombopag, everolimus, fosphenytoin, or lanthanum. Patients will also be encouraged to avoid grape fruit juice and red yeast rice for the duration of the study Atorvastatin is contraindicated during pregnancy and breast-feeding
Interventions	Atorvastatin 40 mg tablet once daily for 6 weeks Placebo (for atorvastatin) 1 tablet once daily for 6 weeks
Outcomes	Primary: change from baseline in endothelial function at 6 weeks Secondary: change from baseline in plasma markers of endothelial activation; change from baseline in heme oxygenase activity; change from baseline in plasma levels of sFLT-1; change from baseline in monocyte activation;change from baseline in renal function; occurrence of AEs; change from baseline in rho/rho kinase activity; change from baseline in plasma levels of VEGF; change from baseline in absolute cell counts; change from baseline in TF expression; change from baseline in TF-mediated sFLT release from monocytes; change from baseline to week 6 in TR jet
Starting date	September 2013
Contact information	Kenneth Ataga, MD, University of North Carolina, Chapel Hill
Notes	Completion date December 2017; R01HL111659 (US NIH Grant/Contract Award Number)

ACE: angiotensin converting enzyme

AEs: adverse events

ALT: alanine aminotransferase

ARB: angiotensin blockers

GGT: gamma glutamyl transferase

INR: International Normalized Ratio

LDL: low-density lipoprotein

PT: prothrombin time

PTT: partial thromboplastin time

sFLT-1: sSoluble fms-like tyrosine kinase-1

TF: tissue factor

TR: tricuspid regurgitant

VEGF: vascular endothelial growth factor