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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by Children's Hospital & Research Center Oakland
Sponsor:
Collaborator:
University of California, Los Angeles
Information provided by (Responsible Party):
Carolyn Hoppe, Children's Hospital & Research Center Oakland
ClinicalTrials.gov Identifier:
NCT01702246
First received: October 4, 2012
Last updated: April 17, 2013
Last verified: April 2013
  Purpose

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: December 2014
Estimated Primary Completion Date: January 2014 (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.

  Eligibility

Ages Eligible for Study:   10 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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) >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 ClinicalTrials.gov identifier: NCT01702246

Contacts
Contact: Carolyn Hoppe, M.D. choppe@mail.cho.org
Contact: Lori Styles, M.D. lstyles@chori.org

Locations
United States, California
Children's Hospital & Research Center Oakland Recruiting
Oakland, California, United States, 94609
Contact: Carolyn Hoppe, M.D.    510-428-3193    choppe@mail.cho.org   
Contact: Lori Styles, M.D.       lstyles@chori.org   
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
Investigators
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

Publications:
Responsible Party: Carolyn Hoppe, Associate Hematologist-Oncologist, Children's Hospital & Research Center Oakland
ClinicalTrials.gov Identifier: NCT01702246     History of Changes
Other Study ID Numbers: DDCF-ICRA-2011
Study First Received: October 4, 2012
Last Updated: April 17, 2013
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Simvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014