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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Dietary supplement: MitoQ

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.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mikhil N Bamne, PhD; Phone Number: (412) 648-6920; Email: bamnemn2@upmc.edu
• Study Contact Backup: Name: Jude Jonassaint, RN; Phone Number: 412-692-2086; Email: jonassaintjc@upmc.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Recruiting
      • Children's Hospital of Pittsburgh
      • Contact: Mikhil N Bamne, PhD; Phone Number: 412-648-6920; Email: bamnemn2@upmc.edu
      • Principal Investigator: Ramasubramanian Kalpatthi, MD
      • Contact: Jude Jonassaint, RN; Phone Number: (412) 692-2086; Email: jonassaintjc@upmc.edu
    • Pittsburgh, Pennsylvania, United States, 15232
      • Recruiting
      • Hillman Cancer Center
      • Contact: Jude Jonassaint, RN; Phone Number: 412-692-2086; Email: jonassaintjc@upmc.edu
      • Contact: Mikhil N Bamne, PhD; Phone Number: 412-648-6920; Email: bamnemn2@upmc.edu
      • Principal Investigator: Ramasubramanian Kalpatthi, MD
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • UPMC Presbyterian
      • Contact: Mikhil N Bamne, PhD; Phone Number: 412-648-6920; Email: bamnemn2@upmc.edu
      • Principal Investigator: Ramasubramanian Kalpatthi, MD
      • Contact: Jude Jonassaint, RN; Phone Number: (412) 692-2086; Email: jonassaintjc@upmc.edu
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • Magee Women's Hospital
      • Contact: Jude Jonassaint, RN; Phone Number: 412-692-2086; Email: jonassaintjc@upmc.edu
      • Contact: Mikhil N Bamne, PhD; Phone Number: 412-648-6920; Email: bamnemn2@upmc.edu
      • Principal Investigator: Ramasubramanian Kalpatthi, MD
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • UPMC Montefiore
      • Contact: Jude Jonassaint, RN; Phone Number: 412-692-2086; Email: jonassaintjc@upmc.edu
      • Contact: Mikhil N Bamne, PhD; Phone Number: 412-648-6920; Email: bamnemn2@upmc.edu
      • Principal Investigator: Ramasubramanian Kalpatthi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Investigators: Principal Investigator: Ramasubramanian Kalpatthi, MD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2020
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: August 27, 2019
• First Submitted That Met QC Criteria: September 27, 2019
• First Posted (Actual): September 30, 2019

Study Record Updates

• Last Update Posted (Actual): June 7, 2024
• Last Update Submitted That Met QC Criteria: June 5, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: MitoQ; Basal platelet activation; mitochondrial ROS (Reactive Oxygen Species)
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: STUDY18120144

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The investigators may share de-identified data with others who are doing similar types of research. All collected individual participant data (IPD), all IPD that underlie results in a publication will be shared.
• IPD Sharing Time Frame: Data will be available 6 months after the publication. July 2022.
• IPD Sharing Access Criteria: The IPD and any additional supporting information will be shared, with other investigators/collaborators when requested. The Principal Investigator will review the requests and will provide the instructions to the research site staff to share the IPD with other investigators.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No