Sickle Cell Disease Clinical Trial
— ENDOOfficial 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)
Verified date | November 2018 |
Source | University of North Carolina, Chapel Hill |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 13 |
Est. completion date | January 9, 2018 |
Est. primary completion date | January 9, 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 60 Years |
Eligibility |
Inclusion Criteria: 1. Sickle cell anemia (HbSS) or Sickle-beta0 thalassemia (HbS-beta0thal) between ages of 18 and 60; 2. albuminuria (micro- or macroalbuminuria, defined as =/> 30mg/g creatinine); 3. serum alanine aminotransferase (ALT) </= 2 times upper limits of normal and/or gamma-glutamyl transferase (GGT) </= 3 times upper limits of normal; 4. platelet count > 150,000 cu/mm; 5. normal baseline coagulation profile (PT, International Normalized Ratio (INR), and PTT); 6. 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; 7. ability to understand the requirements of the study; 8. if a woman of childbearing potential, must use an adequate method of contraception; and 9. if receiving hydroxyurea, ACE inhibitors or angiotensin blockers (ARB), should be on a stable dose for at least 3 months. Exclusion Criteria: 1. hypersensitivity to any component of atorvastatin, or history of adverse reaction to statins; 2. pregnant or breastfeeding; 3. on statin therapy; 4. history of metastatic cancer; 5. current history of alcohol abuse; 6. history of diabetes mellitus or poorly controlled systemic hypertension; 7. end-stage renal disease; 8. total cholesterol level < 80 mg/dL and LDL cholesterol > 130 mg/dL; 9. on a chronic transfusion program; 10. ingested any investigational drugs within the past 4 weeks; 11. prior history of any myopathy; 12. allergy to nitroglycerin; 13. 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. |
Country | Name | City | State |
---|---|---|---|
United States | UNC School of Medicine Clinical&Translational Research Ctr | Chapel Hill | North Carolina |
Lead Sponsor | Collaborator |
---|---|
University of North Carolina, Chapel Hill | National Heart, Lung, and Blood Institute (NHLBI) |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Change From Baseline to Week 6 in Endothelial Function | Endothelial function will be assessed using ultrasound imaging of the brachial artery, with measurement of endothelium-dependent (flow-mediated) and endothelium-independent (nitroglycerin-mediated) dilation of the artery measured in millimeters (mm). | Baseline, 6 weeks | |
Secondary | Change From Baseline to Week 6 in Plasma Markers of Endothelial Activation | Investigators will measure plasma levels of soluble vascular cell adhesion molecules (sVCAM) and soluble intracellular adhesion molecule (sICAM) at baseline and at 6 weeks of treatment. | Baseline, 6 weeks | |
Secondary | Change From Baseline to Week 6 in Heme Oxygenase Activity | The expression and activity of heme oxygenase-1(HO-1)will be determined at baseline and at 6 weeks of treatment. | Baseline, 6 weeks | |
Secondary | Change From Baseline to Week 6 in Plasma Levels of Soluble Fms-like Tyrosine Kinase-1 (sFLT-1) | Investigators will measure plasma levels of soluble fms-like tyrosine kinase-1 (sFLT-1) at baseline and at 6 weeks of treatment. | Baseline, 6 weeks | |
Secondary | Change From Baseline to Week 6 in Monocyte Activation | Flow cytometry performed to assess monocyte activation at baseline and at 6 weeks of treatment. | Baseline, 6 weeks | |
Secondary | Change From Baseline to Week 6 in Renal Function | Investigators will assess the effect of atorvastatin on albuminuria by spot urine microalbuminuria/creatinine ratio measured at baseline and at 6 weeks of treatment. | Baseline, 6 weeks | |
Secondary | Occurrence of Adverse Events. | Subjects will be evaluated for safety by patient self-report of adverse events and results of laboratory tests. | Continuously from randomization through end of study | |
Secondary | Abnormal Physical Findings. | Subjects will be evaluated by physical examination and/or measurement of vital signs at each study visit. | Baseline, 2, 4, and 6 weeks during treatment, and at follow-up. | |
Secondary | Change From Baseline to Week 6 in Rho/Rho Kinase Activity | The expression and activity of rho/rho kinase will be determined at baseline and at 6 weeks of treatment. | Baseline, 6 weeks | |
Secondary | Change From Baseline to Week 6 in Plasma Levels of Vascular Endothelial Growth Factor (VEGF) | Investigators will measure plasma levels of vascular endothelial growth factor (VEGF) at baseline and at 6 weeks of treatment. | Baseline, 6 weeks | |
Secondary | Mean Change From Baseline to Week 6 in Absolute Cell Counts | Flow cytometry will be performed to assess absolute cell counts at baseline and at 6 weeks of treatment. | Baseline, 6 weeks | |
Secondary | Change From Baseline to Week 6 in Tissue Factor (TF) Expression | Flow cytometry will be performed to assess TF expression at baseline and at 6 weeks of treatment. | Baseline, 6 weeks | |
Secondary | Change From Baseline to Week 6 in TF-mediated sFLT Release From Monocytes | Flow cytometry will be performed to assess TF-mediated sFLT release from monocytes at baseline and at 6 weeks of treatment. | Baseline, 6 weeks | |
Secondary | Change From Baseline to Week 6 in Tricuspid Regurgitant (TR) Jet. | Echocardiogram will be used to assess TR jet before and after treatment. | Baseline, Week 6 |
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