MitoQ for Early-phase Schizophrenia-spectrum Disorder and Mitochondrial Dysfunction

NCT06191965 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 2025P000970
• Study Type: interventional
• Target: 100
• Locations: 2 countries
• Sites: 3

Brief Summary

The goal of this double-blind, placebo-controlled randomized clinical trial is to test the effect of 12 weeks of orally administered MitoQ (mitoquinol mesylate) supplementation on cognition in 50 people with early phase schizophrenia-spectrum disorders (E-SSD) who have mitochondrial dysfunction (called high risk, or HR). Cognitive impairments in SSD can cause significant disability. Yet, there are no effective treatments for cognitive impairments in SSD. It has been shown that alterations in a certain type of brain cell (parvalbumin interneurons, or PVI) underlie cognitive deficits in SSD. These PVI, which fire at a fast rate, utilize high amounts of energy from the mitochondria and are highly vulnerable to oxidative stress. MitoQ is an antioxidant. Research has shown that, in mice, MitoQ can reduce oxidative stress in the mitochondria. The main question that this clinical trial aims to answer is:

• Does MitoQ supplementation, compared to placebo, improve cognition in HR patients? Secondary questions that this clinical trial aims to answer are the following: Does MitoQ supplementation, compared to placebo:
• Improve positive and negative symptoms of SSD in HR patients?
• Improve functioning in HR patients?
• Improve/normalize blood markers of mitochondrial dysfunction in HR patients? The investigators will enroll 100 individuals with E-SSD. These enrolled participants will participate in an initial screening visit to determine if they qualify for the actual clinical trial. At the screening visit, the investigators will ask about psychiatric history to determine diagnosis; ask about medical history; do a physical exam; collect blood and urine samples; do a pregnancy test; and ask participants to bring in their current medications in their original packaging so it is known what they are taking. After the screening visit, the investigators will invite 50 HR patients (identified with a blood test) to continue with the clinical trial. Participants who qualify for the clinical trial will be asked to:
• Take a supplement (MitoQ or placebo) once per day for 12 weeks in addition to their usual medications.
• Come in for a study visit every 4 weeks over the 16-week study period. At these study visits, the investigators will do a physical exam; ask about symptoms and side effects; take blood and urine samples; and ask questions about general health and well-being, quality of life, mental health, emotional health, and mood. At visits 1 (baseline) and 4 (12 weeks), participants will also take a cognitive assessment.

Conditions

Schizophrenia and Related Disorders; Mitochondrial Alteration; Cognitive Impairment

Outcome Measures

Primary Outcomes (1)

• Change from baseline in the MATRICS Consensus Cognitive Battery (MCCB) composite score at week 12

  The MCCB evaluates cognitive functioning in schizophrenia and related disorders. It includes ten tests that measure seven cognitive domains including speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. The MCCB composite score has been shown to be highly correlated with general level of intellectual ability.

  Baseline and week 12

Secondary Outcomes (13)

• Change from baseline in the MATRICS Consensus Cognitive Battery (MCCB) attention/vigilance score at week 12

  Baseline and week 12

• Change from baseline in the MATRICS Consensus Cognitive Battery (MCCB) speed of processing score at week 12

  Baseline and week 12

• Change from baseline in the MATRICS Consensus Cognitive Battery (MCCB) working memory score at week 12

  Baseline and week 12

• Change from baseline in the MATRICS Consensus Cognitive Battery (MCCB) verbal learning score at week 12

  Baseline and week 12

• Change from baseline in the MATRICS Consensus Cognitive Battery (MCCB) visual learning score at week 12

  Baseline and week 12

Study Arms (2)

MitoQ

EXPERIMENTAL

20 mg 2 capsules once daily for 12 weeks (total daily dose 40 mg)

Drug: MitoQ

Placebo

PLACEBO COMPARATOR

2 capsules (identical in appearance to MitoQ capsules) once daily for 12 weeks

Drug: Placebo

Interventions

MitoQ DRUG

MitoQ is a synthetic analogue of coenzyme Q10. It is produced by the company Antipodean Pharmaceuticals and is formulated as a stable yellow powder suitable for oral formulation, prepared as capsules of white color. It is a commercial dietary supplement sold over the counter as an antioxidant, to be taken orally once or twice a day. It has subsequently been tested for various clinical conditions in humans. 1. Molecular formula: C38H47O7PS (C37H44O4P.CH3O3S) 2. CAS number: 444890-41-9 (phosphonium cation) 3. Molecular weight: 678.81 4. MitoQ capsules: The standard commercial posology is a 20 mg daily dose. All formulations are produced following Good Manufacturing Practice (GMP) standards (https://www.who.int/medicines/areas/quality\_safety/quality\_assurance/TRS986annex2.pdf?ua=1). 5. MitoQ will be administered in oral capsules provided by the manufacturer Antipodean Pharma, to be taken once daily, one hour before breakfast. The daily dose will be 2 pills, i.e., 40 mg MitoQ.

Also known as: mitoquinol mesylate, Chemical name: [10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl) decyl] triphenyl phosphonium mesylate

MitoQ

Placebo DRUG

Placebo pills in identical appearance to the MitoQ capsules will be produced and provided by Antipodean Pharma and given to the patients in the control arm two per day to be taken one hour before breakfast. The composition of the placebo is tapioca starch, microcrystalline cellulose, hypromellose, silica-colloidal anhydrous, purified water, carrageenan, and pectin.

Also known as: Sugar pill

Placebo

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female aged 18 to 35 years old
• Patients who have been diagnosed with one of the following schizophrenia-spectrum disorders: schizophreniform disorder, schizophrenia, schizoaffective disorder, unspecified psychosis.
• PANSS score \< 75
• Ability to provide informed consent.

You may not qualify if:

• Any acute medical condition requiring actively changing treatment (e.g., autoimmune disorders, acute infections, HIV/AIDS, cancer, renal failure, hepatic dysfunction, cardiovascular disease, or abnormal thyroid findings). Individuals with chronic medical conditions that are stable will not be excluded (e.g., person with hypothyroidism who is taking thyroid hormone replacement and has TSH levels within the normal range; person with well-managed diabetes; etc.)
• Epilepsy or another seizure disorder
• Intellectual disability (e.g., history of IQ \< 70).
• Under legal guardianship
• Not English speaking. The questionnaires, instruments, cognitive assessments used in this research study have not been translated, validated, or studied extensively in non-English-speaking individuals. For this reason, we will not enroll individuals who do not speak English to maintain validity in the study.
• MitoQ allergy
• Treatment with antioxidants: omega3 (fish oil), Vitamin E, Vitamin C, multivitamins, NAC (N-acetyl cysteine) within the last 14 days. If the treatment is taken without prescription, we will ask the patient to stop using it for at least 14 days to become eligible for the present study.
• Children and adolescents, pregnant women, women who have the intention to become pregnant during the course of the study, and breastfeeding women are excluded from the study. This is because no MitoQ pharmacokinetic data are available in pediatric populations, pregnancy or breastfeeding.
• Lack of safe contraception, defined as: female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases. Female participants who are surgically sterilized/hysterectomized or post-menopausal for longer than 2 years are not considered as being of childbearing potential.
• Enrollment of study staff, their family members, and other dependent persons

Sponsors & Collaborators

• Mclean Hospital: lead
• Yale University: collaborator
• University of Lausanne: collaborator

Study Sites (3)

Yale School of Medicine

New Haven, Connecticut, 06519, United States

NOT YET RECRUITING

McLean Hospital

Belmont, Massachusetts, 02478, United States

RECRUITING

University of Lausanne

Lausanne, Switzerland

NOT YET RECRUITING

Related Publications (1)

• Khadimallah I, Jenni R, Cabungcal JH, Cleusix M, Fournier M, Beard E, Klauser P, Knebel JF, Murray MM, Retsa C, Siciliano M, Spencer KM, Steullet P, Cuenod M, Conus P, Do KQ. Mitochondrial, exosomal miR137-COX6A2 and gamma synchrony as biomarkers of parvalbumin interneurons, psychopathology, and neurocognition in schizophrenia. Mol Psychiatry. 2022 Feb;27(2):1192-1204. doi: 10.1038/s41380-021-01313-9. Epub 2021 Oct 22.

  PMID: 34686767 BACKGROUND

MeSH Terms

Conditions

Schizophrenia; Cognitive Dysfunction

Interventions

mitoquinone; Sugars

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Cognition Disorders; Neurocognitive Disorders

Intervention Hierarchy (Ancestors)

Carbohydrates

Study Officials

• Dost Ongur, MD, PhD

  Mclean Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dost Ongur, MD, PhD

CONTACT

6178553922; dongur@mgb.org

Steve Prete, RN

CONTACT

6178552273; sprete@mgb.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The person in charge of the randomization will manage a database with codes matched to the assigned treatment of each patient after the initial screening visit. Trial participants, clinicians, outcome assessors, and researchers involved in the assessments and analyses of collected data will remain blind concerning the MitoQ or placebo randomization. Unblinding is permissible at a clinician's request, for safety reasons, when the health condition of the participant may be or may have been affected by the administration of MitoQ or placebo. In such cases, study staff will find out from the person in charge of randomization which treatment the patient is receiving (MitoQ or placebo) and immediately communicate that information to the patient's clinician. After a participant's allocated intervention has been revealed, however, the subject will be excluded from the trial. The data collected to that point will be included in analyses.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry/Psychotic Disorders Division Chief

Model Details: Randomized controlled trial of MitoQ vs. placebo

Study Record Dates

• First Submitted: December 20, 2023
• First Posted: January 5, 2024
• Study Start: June 1, 2024
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2027
• Last Updated: September 25, 2025

Record last verified: 2025-09

Locations

US (2); CH (1)