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

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

Interventions

DRUG

MitoQ

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.

DRUG

Placebo

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.

Sponsors & Collaborators

• Yale University

  collaborator OTHER

• University of Lausanne

  collaborator OTHER

• Mclean Hospital

  lead OTHER

Principal Investigators

• Dost Ongur, MD, PhD · Mclean Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

35 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-06-01

Primary Completion

2027-01-31

Completion

2027-01-31

FDA Drug

Yes

Countries

• United States
• Switzerland

Study Locations