Effect of Atorvastatin on Endothelial Dysfunction and Albuminuria in Sickle Cell Disease
Condition: Sickle Cell Disease; Sickle Cell Nephropathy
MeSH terms: Kidney Diseases; Albuminuria; Anemia, Sickle Cell
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      It is well recognized that sickle cell disease (SCD) is characterized by a vasculopathy, with
      involvement of multiple organs including the brain, lung, spleen, and kidney. This results in
      multiple clinical complications, including ischemic stroke, pulmonary hypertension,
      autosplenectomy, as well as albuminuria and chronic renal disease. Several recent studies
      have confirmed the association of both albuminuria and renal dysfunction with
      echocardiographically-defined pulmonary hypertension and other vasculopathic complications in
      SCD, suggesting that they may share a similar pathophysiology. Despite the high prevalence of
      albuminuria in patients with SCD and the known association of renal failure with increased
      mortality, the pathophysiology and treatment of albuminuria in this setting remain poorly
      defined.

      The treatment options for nephropathy in SCD are limited. Although Angiotensin converting
      enzyme (ACE) inhibitors are the "standard of care" in the treatment of patients with
      proteinuria, there are to date no controlled, long-term studies confirming their efficacy and
      safety in this setting.

      In this study, the investigators will evaluate the efficacy and safety of atorvastatin in SCD
      patients. At the completion of this trial, the investigators will have an improved
      understanding of the contribution of endothelial dysfunction to the pathophysiology of
      albuminuria in SCD. If the data support the hypothesis that atorvastatin is safe and
      effective in this population, the investigators plan on carrying out adequately powered
      studies to more definitively evaluate its safety and efficacy in the treatment and/or
      prevention of albuminuria in SCD.
    

Intervention name(s): Atorvastatin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 40 mg tablet by mouth daily for 6 weeks; Matching placebo tablet by mouth daily for 6 weeks
Other intervention name(s): Lipitor®; Sugar pill manufactured to mimic atorvastatin 40 mg tablet
Intervention MeSH terms: Atorvastatin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: sickle cell disease; endothelial function; albuminuria; atorvastatin; soluble fms-like tyrosine kinase-1