Effect of Simvastatin Treatment on Vaso-occlusive Pain in Sickle Cell Disease

UCSF Benioff Children's Hospital Oakland

Status and phase

Completed

Phase 2

Phase 1

Conditions

Sickle Cell Disease

Treatments

Drug: Simvastatin

Study type

Interventional

Funder types

Other

Identifiers

NCT01702246

DDCF-ICRA-2011

Details and patient eligibility

About

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.

Full description

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.

Enrollment

24 patients

Sex

All

Ages

10+ years old

Volunteers

No Healthy Volunteers

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