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...
Date First Received: July 26, 2007
Last Updated: March 25, 2008
Verified by: FDA Office of Orphan Products Development, November 2007
Clinical Trial Phase: Phase 1/Phase 2 | Start Date: May 2006
Overall Status: Recruiting
Estimated Enrollment: 36
Brief Summary
Official Title: “Phase I/II Study of Simvastatin (Zocor) Therapy in Sickle Cell Disease”
Condition Keyword(s):
Intervention(s):
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.
Study Type: Interventional
Study Design: Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Detailed Clinical Trial 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.
Intervention(s) in this Clinical Trial
- Drug: Simvastatin
- 20 mg PO once daily for 21 days, followed by a 4-day taper. If this dose is safe and tolerable in the first group of 12 subjects, then the dose will be escalated to 40 mg PO once daily for 21 days, followed by a 4-day taper in the second group of 12 subjects. If the drug is safe and tolerable in this group, then the dose will be escalated to 80 mg PO once daily for 21 days, followed by a 4-day taper in the final group of 12 subjects.
Outcome Measures for this Clinical Trial
Primary 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
- Time Frame: 25 days
Secondary 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
- Time Frame: 25 days
Criteria for Participation in this Clinical Trial
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
Gender Eligibility for this Clinical Trial: Both
Minimum Age for this Clinical Trial: 13 Years
Maximum Age for this Clinical Trial: N/A
Are Healthy Volunteers Accepted for this Clinical Trial?: No
Clinical Trial Sponsor Information
Lead Sponsor: FDA Office of Orphan Products Development
Overall Clinical Trial Officials and Contacts
Carolyn C Hoppe, M.D. Principal Investigator Children's Hospital and Research Center Oakland
Overall Contact: Carolyn C Hoppe, M.D. (510) 428-3193 choppe@mail.cho.org
Related Publications
References
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Additional Information
Information obtained from ClinicalTrials.gov on November 20, 2008
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00508027
Study ID Number: 1R01FD003080-01A1
ClinicalTrials.gov Identifier: NCT00508027
Health Authority: United States: Food and Drug Administration
Children's Hospital and Research Center Oakland Official Website
NHLBI Website - Sickle Cell Disease
Medline Plus: Sickle Cell Anemia
CHO Library: Sickle Cell Disease Information
CHO Sickle Cell Program: National Center for Sickle Cell Disease
Clinical Trials Authorship and Review
Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.
