Sickle Cell Disease
Conditions
Keywords
sickle cell disease, statins, vaso-occlusive pain, inflammation, biomarkers
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.
Interventions
DRUGSimvastatin
40 mg, orally, once daily for 3 months
Sponsors
University of California, Los Angeles
UCSF Benioff Children's Hospital Oakland
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Frequency of Vaso-occlusive Pain Events, Before and After Treatment With Simvastatin | Baseline and 3 months | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in Plasma High Sensitivity C-reactive Protein | Baseline and 3 months | 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 | Baseline and 3 months | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Simvastatin Simvastatin (Zocor), 40mg tablet, 40mg orally once daily, for 3 months
Simvastatin: 40 mg, orally, once daily for 3 months | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Simvastatin |
|---|---|
| Age, Categorical <=18 years | 11 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 18.5 years STANDARD_DEVIATION 6.8 |
| Gender Female | 13 Participants |
| Gender Male | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 18 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Receiving hydroxyurea (HU) therapy | 10 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 19 |
| serious Total, serious adverse events | 5 / 19 |
Outcome results
Primary
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.
Time frame: Baseline and 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline | Change in Frequency of Vaso-occlusive Pain Events, Before and After Treatment With Simvastatin | 0.2365 proportion of pain days | Standard Deviation 0.21 |
| Simvastatin | Change in Frequency of Vaso-occlusive Pain Events, Before and After Treatment With Simvastatin | 0.1311 proportion of pain days | Standard Deviation 0.15 |
p-value: 0.005Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Total Cholesterol Level After Treatment With Simvastatin
Time frame: Baseline and 3 months
Population: change in baseline cholesterol level from baseline, after treatment with simvastatin
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline | Change From Baseline in Total Cholesterol Level After Treatment With Simvastatin | 124 mmol/L | Standard Deviation 27 |
| Simvastatin | Change From Baseline in Total Cholesterol Level After Treatment With Simvastatin | 101 mmol/L | Standard Deviation 17 |
p-value: 0.001t-test, 2 sided
Secondary
Change in Plasma High Sensitivity C-reactive Protein
Mean difference in plasma high sensitivity C-reactive protein level, before and after treatment with simvastatin
Time frame: Baseline and 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline | Change in Plasma High Sensitivity C-reactive Protein | 7.2 mg/mL | Standard Deviation 11 |
| Simvastatin | Change in Plasma High Sensitivity C-reactive Protein | 2.989 mg/mL | Standard Deviation 4.169 |
p-value: 0.003t-test, 2 sided