Phase 2 Completed N=13 Randomized Quadruple-blind Treatment

Effect of Atorvastatin on Endothelial Dysfunction and Albuminuria in Sickle Cell Disease

Sickle Cell Disease · Sickle Cell Nephropathy

Source: ClinicalTrials.gov NCT01732718 ↗

Enrolled (actual)

Serious AEs

15.4%

Results posted

Feb 2019

Primary outcomePrimary: Change From Baseline to Week 6 in Endothelial Function — 1.44; 0.69 % diameter change — p=0.51

Summary

The purpose of this research study is to learn about the effect of the drug, atorvastatin, on blood vessels in patients with sickle cell disease. The primary hypothesis is that endothelial dysfunction is an important contributor to the pathophysiology of albuminuria in SCD. The investigators propose that atorvastatin will improve endothelial dysfunction, decrease levels of soluble fms-like tyrosine kinase-1 (sFLT-1), and decrease albuminuria in SCD patients. Participants will be individuals with sickle cell disease, age 18 to 60, who have some degree of albuminuria. A total of 19 subjects, males and females, will be enrolled. The study is made up of Screening, Treatment, and Follow Up phases and has a cross-over design. After patients are screened for eligibility, they will be randomized to receive atorvastatin or placebo in the initial six-week treatment period. When that is complete, there will be a four-week washout period before they begin another six-week treatment period. In the second treatment period, they "cross-over" to the other treatment arm. Four weeks after the end of the second treatment period, follow-up safety assessments will be done.

Outcome Measures

Outcome	Result	p-value
PRIMARY Change From Baseline to Week 6 in Endothelial Function	1.44; 0.69	0.51
SECONDARY Change From Baseline to Week 6 in Plasma Markers of Endothelial Activation	22.99; 7.54	0.74
SECONDARY Change From Baseline to Week 6 in Heme Oxygenase Activity	—	—
SECONDARY Change From Baseline to Week 6 in Plasma Levels of Soluble Fms-like Tyrosine Kinase-1 (sFLT-1)	19.2; 36.9	0.31
SECONDARY Change From Baseline to Week 6 in Monocyte Activation	—	—
SECONDARY Change From Baseline to Week 6 in Renal Function	28.8; 74.9	0.57
SECONDARY Occurrence of Adverse Events.	9; 13	—
SECONDARY Abnormal Physical Findings.	0; 2; 1; 1; 0; 1	—
SECONDARY Change From Baseline to Week 6 in Rho/Rho Kinase Activity	—	—
SECONDARY Change From Baseline to Week 6 in Plasma Levels of Vascular Endothelial Growth Factor (VEGF)	-3.99; -10.5	0.64
SECONDARY Mean Change From Baseline to Week 6 in Absolute Cell Counts	-0.07; 0.15; 0.08; -0.22; -0.18; -0.55	0.1469
SECONDARY Change From Baseline to Week 6 in Tissue Factor (TF) Expression	—	—
SECONDARY Change From Baseline to Week 6 in TF-mediated sFLT Release From Monocytes	—	—
SECONDARY Change From Baseline to Week 6 in Tricuspid Regurgitant (TR) Jet.	0.80; -0.05	0.5184

Eligibility Criteria

Inclusion Criteria

Sickle cell anemia (HbSS) or Sickle-beta0 thalassemia (HbS-beta0thal) between ages of 18 and 60;
albuminuria (micro- or macroalbuminuria, defined as =/> 30mg/g creatinine);
serum alanine aminotransferase (ALT) 150,000 cu/mm;
normal baseline coagulation profile (PT, International Normalized Ratio (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 enrollment;
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 angiotensin blockers (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 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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01732718). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.