Sickle Cell Disease Clinical Trial
Official title:
Phase I/II Study of Simvastatin (Zocor) Therapy in Sickle Cell Disease
Recent clinical and experimental data indicate that statins have effects beyond cholesterol lowering that may be beneficial in sickle cell disease by protecting the vascular endothelium. Statins have been shown to attenuate endothelial dysfunction through their anti-inflammatory, anti-oxidant and anti-thrombotic properties. This phase I/II dose-escalating trial is designed to assess the safety and potential clinical efficacy of oral simvastatin (Zocor)in adolescents and adults with sickle cell disease (SCD).
Status | Completed |
Enrollment | 42 |
Est. completion date | December 2011 |
Est. primary completion date | December 2011 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 13 Years and older |
Eligibility |
Inclusion Criteria: - Established diagnosis of sickle cell disease (HbSS, SC or Sß-thalassemia) - Age greater than or equal to thirteen years - Weight greater than or equal to 35 kg Exclusion Criteria: - Renal dysfunction (Serum Creatinine > 1.5 UNL) - Hepatic dysfunction (ALT > 2X UNL) - Pretreatment total cholesterol < 100 mg/dL or triglycerides < 30 mg/dL - Pretreatment baseline creatine kinase >1X UNL (215 U/L) - Pregnancy/lactation - RBC transfusion in the last 30 days - Vaso-Occlusive Event needing hospitalization in the past 30 days - Treatment with any statin drugs within the past 30 days - Treatment with drugs having known metabolic interactions with statin drugs (e.g. cytochrome P450 3A4 metabolism), including ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, azithromycin, niacin (nicotinic acid), digoxin, coumadin, sildenafil or amiodarone within the past 30 days - Treatment (past or present) with amiodarone - Musculoskeletal disorder associated with an elevated creatine kinase level - Past or present history of substance abuse (alcohol, cocaine, amphetamines, heroin, PCP) - Allergy to statins |
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | Children's Hospital and Research Center Oakland | Oakland | California |
Lead Sponsor | Collaborator |
---|---|
Children's Hospital & Research Center Oakland | Department of Health and Human Services, FDA Office of Orphan Products Development |
United States,
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Kaul DK, Liu XD, Choong S, Belcher JD, Vercellotti GM, Hebbel RP. Anti-inflammatory therapy ameliorates leukocyte adhesion and microvascular flow abnormalities in transgenic sickle mice. Am J Physiol Heart Circ Physiol. 2004 Jul;287(1):H293-301. Epub 2004 Mar 4. — View Citation
Laufs U, Wassmann S, Hilgers S, Ribaudo N, Böhm M, Nickenig G. Rapid effects on vascular function after initiation and withdrawal of atorvastatin in healthy, normocholesterolemic men. Am J Cardiol. 2001 Dec 1;88(11):1306-7. — View Citation
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Wood KC, Hebbel RP, Granger DN. Endothelial cell P-selectin mediates a proinflammatory and prothrombogenic phenotype in cerebral venules of sickle cell transgenic mice. Am J Physiol Heart Circ Physiol. 2004 May;286(5):H1608-14. Epub 2004 Jan 2. — View Citation
* Note: There are 18 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Change in Plasma NOx Levels | Measurements of the levels of plasma nitric oxide metabolites (NOx), high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1), tissue factor (TF) and vascular endothelial growth factor (VEGF)were performed before and after simvastatin treatment. Changes in mean plasma biomarker levels were assessed for each dose level; however, dose level 3 results were not analyzed, as only 2 subjects were enrolled in this dose group. | Baseline, 21 days | No |
Other | Change in Plasma Hs-CRP Levels | Change in plasma high sensitivity C-reactive protein levels in subjects treated with simvastatin | Baseline, 21 days | No |
Other | Change in Plasma IL-6 Levels | Change in plasma IL-6 level after treatment with simvastatin | Baseline, 21 days | No |
Other | Change in Plasma VEGF Levels | Change in plasma vascular endothelial adhesion molecule-1 levels after treatment with simvastatin | Baseline, 21 days | No |
Other | Change in Plasma VCAM1 Levels | Change in plasma vascular cellular adhesion molecule-1 levels after treatment with simvastatin | Baseline, 21 days | No |
Other | Change in Plasma TF Levels | Change in plasma tissue factor (TF) levels after treatment with simvastatin | Baseline, 21 days | No |
Primary | Change in Total Cholesterol Level | Change in serum total cholesterol level after treatment with simvastatin | Baseline, 21 days | Yes |
Primary | Change in Hemoglobin Level | Change in plasma hemoglobin (Hb) level after treatment with simvastatin | Baseline, 21 days | Yes |
Primary | Change in Serum Creatine Kinase Levels | Change in serum creatine kinase (CK) levels after treatment with simvastatin | Baseline, 21 days | Yes |
Primary | Change in Serum Alanine Transaminase (ALT) Levels | Change in serum alanine transaminase (ALT) after treatment with simvastatin | Baseline, 21 days | Yes |
Primary | Change in Serum Creatinine Levels | Change in serum creatinine (Cr) levels after treatment with simvastatin | Baseline, 21 days | Yes |
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