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

Primary Purpose

Sickle Cell Disease

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Simvastatin
Sponsored by
UCSF Benioff Children's Hospital Oakland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sickle Cell Disease focused on measuring sickle cell disease, statins, vaso-occlusive pain, inflammation, biomarkers

Eligibility Criteria

10 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Children's Hospital and Research Center Oakland

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

simvastatin

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
October 4, 2012
Last Updated
October 26, 2016
Sponsor
UCSF Benioff Children's Hospital Oakland
Collaborators
University of California, Los Angeles
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1. Study Identification

Unique Protocol Identification Number
NCT01702246
Brief Title
Effect of Simvastatin Treatment on Vaso-occlusive Pain in Sickle Cell Disease
Official Title
Phase 2 Study of Simvastatin Treatment Effects on Vaso-occlusive Pain in Sickle Cell Disease
Study Type
Interventional

2. Study Status

Record Verification Date
January 2016
Overall Recruitment Status
Completed
Study Start Date
February 2012 (undefined)
Primary Completion Date
May 2015 (Actual)
Study Completion Date
June 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
UCSF Benioff Children's Hospital Oakland
Collaborators
University of California, Los Angeles

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease
Keywords
sickle cell disease, statins, vaso-occlusive pain, inflammation, biomarkers

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
simvastatin
Arm Type
Experimental
Arm Description
Simvastatin (Zocor), 40mg tablet, 40mg orally once daily, for 3 months
Intervention Type
Drug
Intervention Name(s)
Simvastatin
Other Intervention Name(s)
Zocor
Intervention Description
40 mg, orally, once daily for 3 months
Primary Outcome Measure Information:
Title
Change in Frequency of Vaso-occlusive Pain Events, Before and After Treatment With Simvastatin
Description
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.
Time Frame
Baseline and 3 months
Secondary Outcome Measure Information:
Title
Change in Plasma High Sensitivity C-reactive Protein
Description
Mean difference in plasma high sensitivity C-reactive protein level, before and after treatment with simvastatin
Time Frame
Baseline and 3 months
Title
Change From Baseline in Total Cholesterol Level After Treatment With Simvastatin
Time Frame
Baseline and 3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carolyn Hoppe, MD
Organizational Affiliation
UCSF Benioff Children's Hospital Oakland
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital and Research Center Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
publication
Citations:
PubMed Identifier
21477202
Citation
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.
Results Reference
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Effect of Simvastatin Treatment on Vaso-occlusive Pain in Sickle Cell Disease

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