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

NCT ID: NCT01702246

Last Updated: 2016-12-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2015-06-30

Brief 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.

Detailed 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.

Conditions

Sickle Cell Disease

Keywords

sickle cell disease; statins; vaso-occlusive pain; inflammation; biomarkers

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

simvastatin

Simvastatin (Zocor), 40mg tablet, 40mg orally once daily, for 3 months

Group Type: EXPERIMENTAL

Simvastatin

Intervention Type: DRUG

40 mg, orally, once daily for 3 months

Interventions

Simvastatin

40 mg, orally, once daily for 3 months

Intervention Type: DRUG

Other Intervention Names

Zocor

Eligibility Criteria

Inclusion Criteria

• Sickle cell disease (HbSS or S/β0 thalassemia)
• ≥ 3 vaso-occlusive pain episodes in the year prior to enrollment
• Age ≥ 10 years
• Weight > 30 kg

Exclusion Criteria

• Creatine kinase (CK) > UNL
• Total cholesterol < 90 mg/dL, or triglycerides <30mg/dL
• Renal dysfunction (Creatinine > 1.5-fold UNL)
• Hepatic dysfunction (ALT > 2-fold UNL)
• Treatment with drugs having known metabolic interactions with statins within the past 30 days
• Vaso-occlusive pain requiring hospitalization within past 30 days
• Red blood cell 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)
• 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 electronic pain diary in this study

• Minimum Eligible Age: 10 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, Los Angeles

OTHER

Sponsor Role: collaborator

UCSF Benioff Children's Hospital Oakland

OTHER

Sponsor Role: lead

Responsible Party

Carolyn Hoppe

Associate Hematologist-Oncologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Carolyn Hoppe, MD

Role: PRINCIPAL_INVESTIGATOR

UCSF Benioff Children's Hospital Oakland

Locations

Children's Hospital and Research Center Oakland

Oakland, California, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 21477202 (View on PubMed)

Other Identifiers

DDCF-ICRA-2011

Identifier Type: -

Identifier Source: org_study_id