Simvastatin (Zocor) Therapy in Sickle Cell Disease
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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 |
- 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 ]
- 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 |
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
Contacts and Locations| United States, California | |
| Children's Hospital and Research Center Oakland | |
| Oakland, California, United States, 94609 | |
| Principal Investigator: | Carolyn C Hoppe, M.D. | Children's Hospital & Research Center Oakland |
More Information
Additional Information:
Publications:
| 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 |
Keywords provided by Children's Hospital & Research Center Oakland:
|
sickle cell disease simvastatin statin drugs nitric oxide donors vascular injury |
Additional relevant MeSH terms:
|
Anemia, Sickle Cell Anemia, Hemolytic, Congenital Anemia, Hemolytic Anemia Hematologic Diseases Hemoglobinopathies Genetic Diseases, Inborn Simvastatin Nitric Oxide Donors Hypolipidemic Agents |
Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Lipid Regulating Agents Therapeutic Uses Hydroxymethylglutaryl-CoA Reductase Inhibitors Anticholesteremic Agents Enzyme Inhibitors Cardiovascular Agents |
ClinicalTrials.gov processed this record on October 17, 2012
