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Simvastatin (Zocor) Therapy in Sickle Cell Disease
This study is currently recruiting participants.
Verified by Children's Hospital & Research Center Oakland, December 2009
First Received: July 26, 2007   Last Updated: January 26, 2010   History of Changes
Sponsor: Children's Hospital & Research Center Oakland
Collaborators: Department of Health and Human Services
FDA Office of Orphan Products Development
Information provided by: Children's Hospital & Research Center Oakland
ClinicalTrials.gov Identifier: NCT00508027
  Purpose

This research study focuses on individuals with sickle cell disease (SCD). There is scientific evidence suggesting that treatment with the statin drug, simvastatin (Zocor), may be helpful for people with vascular diseases like SCD. This study looks at the effect this drug may have in preventing injury to the blood vessels. It will check for a change in the levels of certain substances in the blood that can damage blood vessels. The study will also help us find out whether, and at what dose, simvastatin is safe and useful for people with SCD.


Condition Intervention Phase
Sickle Cell Disease
 Drug: Simvastatin
 Phase I
Phase II

Study Type: Interventional
Study Design: Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title: Phase I/II Study of Simvastatin (Zocor) Therapy in Sickle Cell Disease

Resource links provided by NLM:

Genetics Home Reference related topics: sickle cell disease
MedlinePlus related topics: Sickle Cell Anemia Statins
Drug Information available for: Simvastatin
U.S. FDA Resources

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

Primary Outcome Measures:
  • Evaluate the effect of simvastatin on biomarkers of: 1) vasoreactivity (NO, ET-1), 2) endothelial adhesion (VCAM-1), VEGF), and 3) inflammation (CRP, IL-6, TF) in three escalating dosage (low, moderate, and high) groups. [ Time Frame: 25 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and tolerability of simvastatin in patients with sickle cell disease, as measured by changes in clinical (P.E.; adverse affects) and laboratory (hematologic, renal, hepatic and lipid) profiles. [ Time Frame: 25 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 36
Study Start Date: June 2007
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Simvastatin, Dose Escalation
There are no arms in this study. Simvastatin will be given in a dose-escalating fashion to 3 sequential dosage groups (20 mg/day, 40 mg/day, 80 mg/day).
Drug: Simvastatin
Comparison of 3 dosages of simvastatin given in a dose-escalating fashion. 20 mg, 40 mg, or 80 mg PO QD x 21 days followed by a drug taper x 4 days.

Detailed Description:

Although statins have been used extensively for their cholesterol-lowering effects, recent clinical and experimental data indicate that statins regulate yet other processes, many of which play a major role in sickle cell disease (SCD). Independent of their cholesterol-lowering effects, statins have been shown to prevent damage to blood vessels in several ways, including the upregulation of endothelial nitric oxide (NO). Numerous studies documenting the protective effects of statins, together with data showing the therapeutic role of NO in SCD, provide the basis for investigating the potential clinical benefit of simvastatin in SCD.

Data supporting the safety and tolerability of simvastatin in patients with SCD are now needed. For this phase I/II dose-escalation study of oral simvastatin in SCD, we propose the following specific aims:

  1. To determine specific dose-response effects of oral simvastatin on patients with SCD, and
  2. To assess the safety and tolerability of oral simvastatin in patients with SCD.
  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age greater than or equal to thirteen years
  • Weight greater than or equal to 35 kg

Exclusion Criteria:

  • Serum Creatinine > 1.5 UNL
  • ALT > 2X UNL
  • Pretreatment Cholesterol < 100mg/dl
  • Pregnancy/lactation
  • RBC transfusion in the last 30 days
  • Vaso-Occlusive Event needing hospitalization in the past 30 days
  • Used Statin drugs within the past 30 days
  • Treatment with drugs having metabolic interactions with statin drugs
  • Musculoskeletal disorder with elevated creatine kinase
  • Allergy to statins
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00508027

Contacts
Contact: Carolyn C Hoppe, M.D. (510) 428-3193 choppe@mail.cho.org
Contact: Susan M Shaheen, MS (510) 428-3885 ext 2607 sshaheen@mail.cho.org

Locations
United States, California
Children's Hospital and Research Center Oakland Recruiting
Oakland, California, United States, 94609
Contact: Carolyn C Hoppe, M.D.     510-428-3193     choppe@mail.cho.org    
Contact: Susan M Shaheen, MS     (510) 428-3885 ext 2607     sshaheen@mail.cho.org    
Principal Investigator: Carolyn C Hoppe, M.D.            
Sponsors and Collaborators
Children's Hospital & Research Center Oakland
Department of Health and Human Services
FDA Office of Orphan Products Development
Investigators
Principal Investigator: Carolyn C Hoppe, M.D. Children's Hospital and Research Center Oakland
  More Information

Additional Information:
Children's Hospital and Research Center Oakland Official Website  This link exits the ClinicalTrials.gov site
NHLBI Website - Sickle Cell Disease  This link exits the ClinicalTrials.gov site
Medline Plus: Sickle Cell Anemia  This link exits the ClinicalTrials.gov site
CHO Library: Sickle Cell Disease Information  This link exits the ClinicalTrials.gov site
CHO Sickle Cell Program: National Center for Sickle Cell Disease  This link exits the ClinicalTrials.gov site

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Graido-Gonzalez E, Doherty JC, Bergreen EW, Organ G, Telfer M, McMillen MA. Plasma endothelin-1, cytokine, and prostaglandin E2 levels in sickle cell disease and acute vaso-occlusive sickle crisis. Blood. 1998 Oct 1;92(7):2551-5.
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Brown MD, Wick TM, Eckman JR. Activation of vascular endothelial cell adhesion molecule expression by sickle blood cells. Pediatr Pathol Mol Med. 2001 Jan-Feb;20(1):47-72.
Jison ML, Munson PJ, Barb JJ, Suffredini AF, Talwar S, Logun C, Raghavachari N, Beigel JH, Shelhamer JH, Danner RL, Gladwin MT. Blood mononuclear cell gene expression profiles characterize the oxidant, hemolytic, and inflammatory stress of sickle cell disease. Blood. 2004 Jul 1;104(1):270-80. Epub 2004 Mar 18.
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Responsible Party: Children's Hospital and Research Center Oakland ( Carolyn Hoppe, M.D. )
Study ID Numbers: 1R01FD003080-01A1
Study First Received: July 26, 2007
Last Updated: January 26, 2010
ClinicalTrials.gov Identifier: NCT00508027     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Hospital & Research Center Oakland:
sickle cell disease
simvastatin
statin drugs
nitric oxide donors
vascular injury

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

ClinicalTrials.gov processed this record on February 08, 2010



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