Simvastatin (Zocor) Therapy in Sickle Cell Disease - Full Text View

Sponsor:	Children's Hospital & Research Center Oakland
Collaborators:	Department of Health and Human Services FDA Office of Orphan Products Development
Information provided by (Responsible Party):	Carolyn Hoppe, Children's Hospital & Research Center Oakland
ClinicalTrials.gov Identifier:	NCT00508027

Sponsor:

Children's Hospital & Research Center Oakland

Collaborators:

Department of Health and Human Services
FDA Office of Orphan Products Development

Information provided by (Responsible Party):

Carolyn Hoppe, 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 1 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 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: Nitric oxide 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 plasma biomarkers of endothelial activation in three escalating treatment dosage (20mg/day,40mg/day,80mg/day) 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 adverse affects and laboratory (hematologic, renal, hepatic and lipid) profiles. [ Time Frame: 25 days ] [ Designated as safety issue: Yes ]

Enrollment:	28
Study Start Date:	June 2007
Study Completion Date:	December 2011
Primary Completion Date:	December 2011 (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. Other Name: Zocor

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, through upregulation of endothelial nitric oxide (NO)and decreased inflammation. 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:

To determine specific dose-response effects of oral simvastatin on patients with SCD, and
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:

Established diagnosis of sickle cell disease (HbSS, SC or Sβ-thalassemia)
Age greater than or equal to thirteen years
Weight greater than or equal to 35 kg

Exclusion Criteria:

Renal dysfunction (Serum Creatinine > 1.5 UNL)
Hepatic dysfunction (ALT > 2X UNL)
Pretreatment total cholesterol < 100 mg/dL or triglycerides < 30 mg/dL
Pretreatment baseline creatine kinase >1X UNL (215 U/L)
Pregnancy/lactation
RBC transfusion in the last 30 days
Vaso-Occlusive Event needing hospitalization in the past 30 days
Treatment with any statin drugs within the past 30 days
Treatment with drugs having known metabolic interactions with statin drugs (e.g. cytochrome P450 3A4 metabolism), including ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, azithromycin, niacin (nicotinic acid), digoxin, coumadin, sildenafil or amiodarone within the past 30 days
Treatment (past or present) with amiodarone
Musculoskeletal disorder associated with an elevated creatine kinase level
Past or present history of substance abuse (alcohol, cocaine, amphetamines, heroin, PCP)
Allergy to statins

Responsible Party:	Carolyn Hoppe, Associate Hematologist, Children's Hospital & Research Center Oakland
ClinicalTrials.gov Identifier:	NCT00508027 History of Changes
Other Study ID Numbers:	1R01FD003080-01A1
Study First Received:	July 26, 2007
Last Updated:	February 9, 2012
Health Authority:	United States: Food and Drug Administration

United States, California
Children's Hospital and Research Center Oakland
Oakland, California, United States, 94609