MitoQ for Sickle Cell Disease

(MitoQ Trial)

Recruiting at 4 trial locations

Overseen By Mikhil N Bamne, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Pittsburgh

Must not be taking: Anti-platelet

Disqualifiers: Pregnancy, Hypertension, Hemodialysis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

15 Participants Needed

Trial Summary

What is the purpose of this trial?

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).

Will I have to stop taking my current medications?

The trial requires that you stop taking anti-platelet medications at least 4 weeks before joining. If you're on such medications, you'll need to stop them to participate.

How is the drug MitoQ different from other treatments for sickle cell disease?

MitoQ is unique because it is a mitochondria-targeted antioxidant, which means it specifically targets and protects the energy-producing parts of cells from damage. This approach is different from other treatments for sickle cell disease, which typically focus on managing symptoms or preventing complications rather than directly protecting cellular components. ^{1 2 3 4 5}

Research Team

Ramasubramanian Kalpatthi, MD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for African American adults over 18 with sickle cell anemia. Healthy African American adults can also participate as controls. People cannot join if they are pregnant, have known high blood pressure, use anti-platelet medication, had a transfusion within the last month, require hemodialysis or treatment for obstructive sleep apnea.

Inclusion Criteria

I am 18 years old or older.

None. (This criterion is not acceptable in a clinical trial as it is discriminatory.)

The study is not looking for African American healthy individuals.

Exclusion Criteria

I have not used anti-platelet medication or had a transfusion in the last 4 weeks.

You are pregnant.

I have been diagnosed with high blood pressure.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral MitoQ (20mg once a day) for 14 days to assess its effect on platelet function and vascular dysfunction in SCA patients

2 weeks

Baseline and end of treatment visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and changes in blood pressure and hemolytic markers

4 weeks

Treatment Details

Interventions

• MitoQ

Trial Overview The study is testing MitoQ, an antioxidant supplement not yet studied in sickle cell disease patients. It aims to see if MitoQ can improve how platelets function and reduce harmful oxygen-related molecules in those with sickle cell disease.

Participant Groups

Group I: Sickle cell patients Experimental Treatment 1 Intervention

Sickle Cell subjects administered oral MitoQ (20mg once a day for 14 days)

Group II: Non Sickle cell Control subjects Active Control 1 Intervention

Normal control subjects administered oral MitoQ (20mg once a day for 14 days)

Who Is Running the Clinical Trial?

University of Pittsburgh

Lead Sponsor

Trials

1,820

Recruited

16,360,000+

Findings from Research

A sensitive and accurate liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay was developed to measure mitoquinone levels and its metabolites in rat plasma, demonstrating a linear calibration curve and a low limit of quantitation (0.5 ng/mL).

The pharmacokinetic study identified four metabolites of MitoQ10 in rat plasma, suggesting that MitoQ10 is effectively processed in the body, which is important for understanding its potential therapeutic effects in neurodegenerative diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitation and metabolism of mitoquinone, a mitochondria-targeted antioxidant, in rat by liquid chromatography/tandem mass spectrometry. Li, Y., Zhang, H., Fawcett, JP., et al.[2018]

Mitoquinone (MitoQ(10)) is effectively absorbed in the intestines, with 18-41% of the administered dose accumulating intracellularly, indicating its potential as a treatment for neurodegenerative diseases.

The absorption of MitoQ(10) can be significantly enhanced by the presence of serum proteins like bovine serum albumin, suggesting that its bioavailability may improve in real-life conditions despite some limitations from metabolism and transport proteins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transport and metabolism of MitoQ10, a mitochondria-targeted antioxidant, in Caco-2 cell monolayers. Li, Y., Fawcett, JP., Zhang, H., et al.[2018]

MitoQ, a targeted antioxidant, effectively reduces oxidative DNA damage in T lymphocytes from older adults when exposed to oxidative stress, indicating its potential to improve immune function with age.

Higher concentrations of mitoQ (0.5 and 1.0 μM) significantly decreased endogenous DNA damage, suggesting that it may help combat age-related decline in immune cell function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An investigation of the effects of MitoQ on human peripheral mononuclear cells. Marthandan, S., Murphy, MP., Billett, E., et al.[2021]

MitoQ, a mitochondria-targeted antioxidant, significantly reduced inflammation and oxidative stress in a mouse model of colitis, indicating its potential as a treatment for inflammatory bowel disease.

The study found that MitoQ decreased levels of harmful inflammatory cytokines IL-1 beta and IL-18, and suppressed the activation of the NLRP3 inflammasome, which plays a key role in inflammation, suggesting a mechanism for its therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitochondria-targeted antioxidant MitoQ ameliorates experimental mouse colitis by suppressing NLRP3 inflammasome-mediated inflammatory cytokines. Dashdorj, A., Jyothi, KR., Lim, S., et al.[2021]

In a study using a humanized mouse model of chronic HIV infection, treatment with the mitochondrial antioxidant MitoQ alongside antiretroviral therapy for 90 days improved mitochondrial function, as indicated by higher ratios of mitochondrial to nuclear DNA in end organs.

This research provides promising evidence that MitoQ could be a potential treatment for mitochondrial dysfunction associated with HIV, which currently has no existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitoquinone Mesylate and Mitochondrial DNA in End Organs in Humanized Mouse Model of Chronic Treated Human Immunodeficiency Virus Infection. Song, S., Satta, S., Sharma, MB., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Quantitation and metabolism of mitoquinone, a mitochondria-targeted antioxidant, in rat by liquid chromatography/tandem mass spectrometry. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Transport and metabolism of MitoQ10, a mitochondria-targeted antioxidant, in Caco-2 cell monolayers. [2018]

3. England pubmed.ncbi.nlm.nih.gov

An investigation of the effects of MitoQ on human peripheral mononuclear cells. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Mitochondria-targeted antioxidant MitoQ ameliorates experimental mouse colitis by suppressing NLRP3 inflammasome-mediated inflammatory cytokines. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Mitoquinone Mesylate and Mitochondrial DNA in End Organs in Humanized Mouse Model of Chronic Treated Human Immunodeficiency Virus Infection. [2023]