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

Sickle Cell Disease Clinical Trial

Official title:

Phase 2 Study of Simvastatin Treatment Effects on Vaso-occlusive Pain in Sickle Cell Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01702246
• Other study ID #: DDCF-ICRA-2011
• Status: Recruiting
• Phase: Phase 2
• First received: October 4, 2012
• Last updated: February 2, 2015
• Start date: February 2012
• Est. completion date: June 2015

Study information

• Verified date: February 2015
• Source: Children's Hospital & Research Center Oakland
• Contact: Carolyn Hoppe, M.D.
• Email: choppe[@]mail.cho.org
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: June 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 10 Years and older

Eligibility

Inclusion Criteria:

• Sickle cell disease (HbSS or S/ß0 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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Drug:
• Simvastatin
40 mg, orally, once daily for 3 months

Locations

Country	Name	City	State
United States	Children's Hospital & Research Center Oakland	Oakland	California

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital & Research Center Oakland	University of California, Los Angeles

Country where clinical trial is conducted

United States, 

References & Publications (1)

Hoppe C, Kuypers F, Larkin S, Hagar W, Vichinsky E, Styles L. A pilot study of the short-term use of simvastatin in sickle cell disease: effects on markers of vascular dysfunction. Br J Haematol. 2011 Jun;153(5):655-63. doi: 10.1111/j.1365-2141.2010.08480.x. Epub 2011 Apr 8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Vaso-occlusive pain events	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.	4 months	No
Secondary	Correlation of plasma biomarkers with clinical measures of vaso-occlusive pain	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.	4 months	No
Secondary	Clinical safety of simvastatin	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.	4 months	Yes