Effect of MitoQ on Platelet Function and Reactive Oxygen Species Generation in Patients With Sickle Cell Anemia

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effect of MitoQ on Platelet Function and Reactive Oxygen Species (ROS) Generation in Patients With Sickle Cell Anemia

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Dietary Supplement: MitoQ


Participation Criteria
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Eligibility Criteria
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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: Pregnancy, Known hypertension, Hemodialysis and active obstructive sleep apnea requiring treatment. Use of anti-platelet medication or have had transfusion in the 4 weeks prior to enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Non randomized case control study design.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sickle cell patients<br>Sickle Cell subjects administered oral MitoQ (20mg once a day for 14 days) | Dietary Supplement: MitoQ<br>* Oral; 20mg once a day for 14 days<br>|
| Active Comparator: Non Sickle cell Control subjects<br>Normal control subjects administered oral MitoQ (20mg once a day for 14 days) | Dietary Supplement: MitoQ<br>* Oral; 20mg once a day for 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of MitoQ on platelet activation markers in subjects with SCA | 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) | Baseline to 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of MitoQ on vascular dysfunction in subjects with SCA | Changes in both systolic and diastolic blood pressure will be measured during the study period | Baseline to 14 days | 
| Effect of MitoQ on hemolysis in subjects with SCA | Changes in plasma free hemoglobin level (mg/dL) will be measured in blood. | Baseline to 14 days | 
| Effect of MitoQ on hemolysis in subjects with SCA | Changes in plasma adenosine diphosphate level (micromole/liter) will be measured in blood. | Baseline to 14 days | 
| Effect of MitoQ on hemolysis in subjects with SCA | Changes in serum lactate dehydrogenase level (units/L) will be measured in blood. | Baseline to 14 days | 
| Treatment related severe adverse events (SAE) | Overall incidence of treatment emergent severe adverse events (SAE) | Baseline to 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MitoQ, Basal platelet activation, mitochondrial ROS (Reactive Oxygen Species)