Phase 2 Study of Simvastatin Treatment Effects on Vaso-occlusive Pain in Sickle Cell Disease
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Change in Frequency of Vaso-occlusive Pain Events, Before and After Treatment With Simvastatin
Study Overview
Brief Summary
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
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 10 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
simvastatin
Simvastatin (Zocor), 40mg tablet, 40mg orally once daily, for 3 months
Intervention: Simvastatin (Drug)
Outcomes
Primary Outcomes
Change in Frequency of Vaso-occlusive Pain Events, Before and After Treatment With Simvastatin
Time Frame: Baseline and 3 months
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.
Secondary Outcomes
- Change in Plasma High Sensitivity C-reactive Protein(Baseline and 3 months)
- Change From Baseline in Total Cholesterol Level After Treatment With Simvastatin(Baseline and 3 months)
Investigators
Carolyn Hoppe
Associate Hematologist-Oncologist
UCSF Benioff Children's Hospital Oakland