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

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

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.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: Simvastatin

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: simvastatin; Simvastatin (Zocor), 40mg tablet, 40mg orally once daily, for 3 months	Drug: Simvastatin; 40 mg, orally, once daily for 3 months; Other Names: Zocor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Frequency of Vaso-occlusive Pain Events, Before and After Treatment With Simvastatin	The effect of simvastatin treatment will be assessed by measuring the difference from baseline in the mean frequency (and intensity) of vaso-occlusive pain events, after treatment with simvastatin. Pain rate (proportion of pain days) was defined as the number of days reported with sickle cell disease-related pain divided by the number of daily pain diaries completed.	Baseline and 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Plasma High Sensitivity C-reactive Protein	Mean difference in plasma high sensitivity C-reactive protein level, before and after treatment with simvastatin	Baseline and 3 months
Change From Baseline in Total Cholesterol Level After Treatment With Simvastatin		Baseline and 3 months

Collaborators and Investigators

• Sponsor: UCSF Benioff Children's Hospital Oakland
• Collaborators: University of California, Los Angeles
• Investigators: Principal Investigator: Carolyn Hoppe, MD, UCSF Benioff Children's Hospital Oakland

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: October 4, 2012
• First Submitted That Met QC Criteria: October 5, 2012
• First Posted (Estimate): October 8, 2012

Study Record Updates

• Last Update Posted (Estimate): December 19, 2016
• Last Update Submitted That Met QC Criteria: October 26, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: biomarkers; inflammation; sickle cell disease; statins; vaso-occlusive pain
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: DDCF-ICRA-2011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: publication