Sickle Cell Disease
Conditions
Keywords
Basal platelet activation, MitoQ, mitochondrial ROS (Reactive Oxygen Species)
Brief summary
MitoQ is commercially available as a dietary supplement and it has been tested as a potential drug in other diseases, but it has never been tested in patients with sickle cell disease. The goal of this research is to study if MitoQ, a molecule that works as an antioxidant by removing potentially damaging agents in a living organism, improves platelet function in patients with sickle cell disease (SCD).
Detailed description
Antioxidant therapies targeted to specific enzymes or compartments may be beneficial in sickle cell anemia (SCA). MitoQ, the most extensively studied mitochondrial-targeted antioxidant, has been shown to be protective against ischemia/reperfusion injury in the heart, endothelial damage due to hypertension and ROS in animal models. MitoQ is commercially available as a dietary supplement to reduce overall oxidative stress and anti-ageing. However, MitoQ has not been tested either as a platelet antagonist or as an endothelial protectant in SCA patients. Investigators propose to conduct a small clinical trial of MitoQ in subjects with SCA to test the hypothesis that MitoQ scavenges platelet mtROS to prevent platelet activation and attenuate vascular dysfunction in SCA. Investigators will test whether MitoQ decreases basal platelet activation in SCD patients and attenuates vascular dysfunction in subjects with SCA. Investigators will administer MitoQ orally to patients and healthy controls for 14 days. Investigators will obtain platelet count, hemolytic markers, platelet mtROS levels and activation markers, clinic BP measurements before and after MitoQ. Adult male and female SCA subjects in steady state (n=10) and 5 healthy African-American volunteers will be recruited after obtaining informed consent.
Interventions
DIETARY_SUPPLEMENTMitoQ
Oral; 20mg once a day for 14 days
Sponsors
University of Pittsburgh
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Non randomized case control study design.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Subjects * African American * Patients with sickle cell anemia * 18 years old or older Control * African American healthy controls * 18 years of age or older
Exclusion criteria
1. Pregnancy, 2. Known hypertension, 3. Hemodialysis and active obstructive sleep apnea requiring treatment. 4. Use of anti-platelet medication or have had transfusion in the 4 weeks prior to enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of MitoQ on platelet activation markers in subjects with SCA | Baseline to 14 days | Change in the percentage of platelet activation markers in blood will be measured (p-selectin, activated GpIIb/IIIa expression, platelet mtROS \[mitochondrial reactive oxygen species\], platelet bioenergetics, mitochondrial Complex V activity) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of MitoQ on vascular dysfunction in subjects with SCA | Baseline to 14 days | Changes in both systolic and diastolic blood pressure will be measured during the study period |
| Effect of MitoQ on hemolysis in subjects with SCA | Baseline to 14 days | Changes in plasma free hemoglobin level (mg/dL) will be measured in blood. |
| Treatment related severe adverse events (SAE) | Baseline to 14 days | Overall incidence of treatment emergent severe adverse events (SAE) |
Countries
United States
Contacts
Primary ContactMikhil N Bamne, PhD
Backup ContactJude Jonassaint, RN
Outcome results
None listed