Effect of Simvastatin Treatment on Vaso-occlusive Pain in Sickle Cell Disease
Effect of Simvastatin Treatment on Vaso-occlusive Pain in Sickle Cell Disease
The purpose of this study is to determine whether simvastatin is effective in reducing the
 frequency and intensity of vaso-occlusive pain episodes in patients with sickle cell disease.
Sickle cell disease (SCD) is characterized by recurrent vaso-occlusive episodes and a chronic
 inflammatory state leading to progressive multi-organ injury. The pathophysiology of SCD is
 related to endothelial dysfunction driven largely by impaired nitric oxide (NO) homeostasis
 and chronic inflammation. Through multiple mechanisms, including upregulation of NO, statins
 have been shown to confer protection from endothelial injury, independent of their
 cholesterol-lowering properties.

 By inhibiting inflammation and several common pathways leading to vascular damage,simvastatin
 may help prevent the acute and chronic complications of SCD. The objective of this study is
 to determine whether our preliminary results showing simvastatin-associated reductions in
 plasma markers of vascular injury will translate into a reduction in vaso-occlusive pain
 episodes in patients with SCD. A web-based, smartphone-accessible electronic pain diary will
 be used to monitor frequency and intensity of vaso-occlusive pain in SCD patients treated
 with a single daily dose of simvastatin.
Inclusion Criteria:

 -  Sickle cell disease (HbSS or S/β0 thalassemia)

 -  ≥ 3 vaso-occlusive pain episodes in the year prior to enrollment

 -  Age ≥ 10 years

 -  Weight > 30 kg

 Exclusion Criteria:

 -  Creatine kinase (CK) > UNL

 -  Total cholesterol < 90 mg/dL, or triglycerides <30mg/dL

 -  Renal dysfunction (Creatinine > 1.5-fold UNL)

 -  Hepatic dysfunction (ALT > 2-fold UNL)

 -  Treatment with drugs having known metabolic interactions with statins within the past
 30 days

 -  Vaso-occlusive pain requiring hospitalization within past 30 days

 -  Red blood cell transfusion within the past 30 days

 -  Pregnancy/lactation

 -  Musculoskeletal disorder associated with an elevated CK level

 -  Past or present history of substance abuse (alcohol, cocaine, amphetamines, heroin)

 -  Chronic pain caused by avascular necrosis of the bone (AVN) or leg ulcers, and pain
 due to trauma or causes other than SCD.

 -  Major cognitive or neurological impairments that may hamper the ability to use the
 smartphone or complete the electronic pain diary in this study