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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2015 by Children's Hospital & Research Center Oakland
University of California, Los Angeles
Information provided by (Responsible Party):
Carolyn Hoppe, Children's Hospital & Research Center Oakland Identifier:
First received: October 4, 2012
Last updated: February 2, 2015
Last verified: February 2015
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.

Condition Intervention Phase
Sickle Cell Disease
Drug: Simvastatin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Study of Simvastatin Treatment Effects on Vaso-occlusive Pain in Sickle Cell Disease

Resource links provided by NLM:

Further study details as provided by Children's Hospital & Research Center Oakland:

Primary Outcome Measures:
  • Vaso-occlusive pain events [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    The effect of simvastatin treatment will be assessed by measuring changes in the frequency and intensity of vaso-occlusive pain events from baseline in subjects treated with simvastatin.

Secondary Outcome Measures:
  • Correlation of plasma biomarkers with clinical measures of vaso-occlusive pain [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    Changes in plasma biomarkers of vascular injury (NOx, IL-6, hs-CRP, VCAM-1, ICAM-1, E-selectin, VEGF) will be correlated with changes in vaso-occlusive pain within subjects at baseline and multiple timepoints during and after treatment with simvastatin.

  • Clinical safety of simvastatin [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
    Clinical and laboratory monitoring for simvastatin-related adverse effects, including myopathy, will be monitored closely in all subjects. Clinical safety outcomes to be measured include changes in serum chemistries and blood cell counts, medication use and specific adverse events.

Estimated Enrollment: 25
Study Start Date: February 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: simvastatin
Simvastatin (Zocor), 40mg tablet, 40mg orally once daily, for 3 months
Drug: Simvastatin
40 mg, orally, once daily for 3 months
Other Name: Zocor

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.


Ages Eligible for Study:   10 Years and older   (Child, Adult, Senior)
Genders Eligible for Study:   Both
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) >1X UNL
  • Total cholesterol < 90 mg/dL, or TG <30mg/dL
  • Renal dysfunction (Creatinine > 1.5X UNL)
  • Hepatic dysfunction (ALT > 2X UNL)
  • Treatment with drugs having known metabolic interactions with statins (e.g.cytochrome P450 3A4 metabolism or amiodarone) within the past 30 days
  • Vaso-occlusive pain requiring hospitalization within past 30 days
  • RBC 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, PCP)
  • 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 eDiary in this study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01702246

Contact: Carolyn Hoppe, M.D.
Contact: Lori Styles, M.D.

United States, California
Children's Hospital & Research Center Oakland Recruiting
Oakland, California, United States, 94609
Contact: Carolyn Hoppe, M.D.    510-428-3193   
Contact: Lori Styles, M.D.   
Principal Investigator: Carolyn Hoppe, M.D.         
Sub-Investigator: Lori Styles, M.D.         
Sub-Investigator: Frans Kuypers, Ph.D.         
Sponsors and Collaborators
Children's Hospital & Research Center Oakland
University of California, Los Angeles
Principal Investigator: Carolyn Hoppe, MD Children's Hospital & Research Center Oakland
Study Chair: Elliott P Vichinsky, MD Children's Hospital & Research Center Oakland
  More Information

Responsible Party: Carolyn Hoppe, Associate Hematologist-Oncologist, Children's Hospital & Research Center Oakland Identifier: NCT01702246     History of Changes
Other Study ID Numbers: DDCF-ICRA-2011 
Study First Received: October 4, 2012
Last Updated: February 2, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Hospital & Research Center Oakland:
sickle cell disease
vaso-occlusive pain

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hematologic Diseases
Genetic Diseases, Inborn
Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors processed this record on October 25, 2016