Clinical trial NCT01702246: Effect of Simvastatin Treatment on Vaso-occlusive Pain in Sickle Cell Disease
Official title: Phase 2 Study of Simvastatin Treatment Effects on Vaso-occlusive Pain in Sickle Cell Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Sickle Cell Disease
Keywords: sickle cell disease
statins
vaso-occlusive pain
inflammation
biomarkers
Lead sponsor: UCSF Benioff Children's Hospital Oakland
Sponsor class: OTHER
Collaborators: name: University of California, Los Angeles
First posted: 2012-10-08
Enrollment: 24
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Frequency of Vaso-occlusive Pain Events, Before and After Treatment With Simvastatin
timeFrame: Baseline and 3 months
Secondary outcomes:
measure: Change in Plasma High Sensitivity C-reactive Protein
timeFrame: Baseline and 3 months
measure: Change From Baseline in Total Cholesterol Level After Treatment With Simvastatin
timeFrame: Baseline and 3 months
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Children's Hospital and Research Center Oakland
state: California
Study officials:
affiliation: UCSF Benioff Children's Hospital Oakland
name: Carolyn Hoppe, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hoppe C, Kuypers F, Larkin S, Hagar W, Vichinsky E, Styles L. A pilot study of the short-term use of simvastatin in sickle cell disease: effects on markers of vascular dysfunction. Br J Haematol. 2011 Jun;153(5):655-63. doi: 10.1111/j.1365-2141.2010.08480.x. Epub 2011 Apr 8.