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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase 2 Study of Simvastatin Treatment Effects on Vaso-occlusive Pain in Sickle Cell Disease

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: Simvastatin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: simvastatin<br>Simvastatin (Zocor), 40mg tablet, 40mg orally once daily, for 3 months | Drug: Simvastatin<br>* 40 mg, orally, once daily for 3 months<br>* Other names: Zocor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Frequency of Vaso-occlusive Pain Events, Before and After Treatment With Simvastatin | The effect of simvastatin treatment will be assessed by measuring the difference from baseline in the mean frequency (and intensity) of vaso-occlusive pain events, after treatment with simvastatin. Pain rate (proportion of pain days) was defined as the number of days reported with sickle cell disease-related pain divided by the number of daily pain diaries completed. | Baseline and 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Plasma High Sensitivity C-reactive Protein | Mean difference in plasma high sensitivity C-reactive protein level, before and after treatment with simvastatin | Baseline and 3 months | 
| Change From Baseline in Total Cholesterol Level After Treatment With Simvastatin |  | Baseline and 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sickle cell disease, statins, vaso-occlusive pain, inflammation, biomarkers