MitoQ for Schizophrenia

Recruiting at 2 trial locations

Overseen By Dost Ongur, MD, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Mclean Hospital

Must be taking: Antipsychotics

Must not be taking: Antioxidants

Disqualifiers: Substance use disorder, Epilepsy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 12 weeks

100 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

You can continue taking your usual medications during the trial, but you must stop taking any antioxidant supplements like omega-3, Vitamin E, Vitamin C, multivitamins, or NAC at least 14 days before starting the study.

How does the drug MitoQ differ from other treatments for schizophrenia?

MitoQ is unique because it targets mitochondrial dysfunction, which is not a focus of traditional antipsychotic treatments for schizophrenia. This approach may offer a novel way to address symptoms by improving cellular energy production and reducing oxidative stress, which are not typically targeted by existing medications. ^{1 2 3 4 5}

Research Team

Dost Ongur, MD, PhD

Principal Investigator

Mclean Hospital

Eligibility Criteria

This trial is for individuals with early-phase schizophrenia-spectrum disorders who also show signs of mitochondrial dysfunction. To join, they must pass a screening that includes psychiatric and medical history reviews, physical exams, and blood tests to confirm high-risk status.

Inclusion Criteria

I have been diagnosed with a type of schizophrenia or related disorder.

I am between 18 and 35 years old.

Less than five years in treatment for psychosis (note that the duration of psychosis may be longer than 5 years, but this is more difficult to ascertain and therefore less reliable as an inclusion criterion)

Exclusion Criteria

MitoQ allergy

Meeting DSM-5 criteria for any substance use disorder diagnosis in the past 6 months will be exclusionary EXCEPT tobacco and mild/moderate cannabis use disorder, which will be included

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive MitoQ or placebo supplementation once daily for 12 weeks

12 weeks

4 visits (in-person) every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• MitoQ
• Placebo

Trial Overview The study is testing if MitoQ (an antioxidant supplement) can improve cognition in patients over a 12-week period compared to a placebo. Participants will continue their usual medications while adding the supplement or placebo.

Participant Groups

Group I: MitoQ Experimental Treatment 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

Mclean Hospital

Lead Sponsor

Trials

221

Recruited

22,500+

Yale University

Collaborator

Trials

1,963

Recruited

3,046,000+

University of Lausanne

Collaborator

Trials

108

Recruited

37,700+

Findings from Research

In a meta-regression analysis of 18 double-blind, randomized, placebo-controlled trials involving 998 patients with stable schizophrenia, drugs were found to be more effective than placebo in reducing negative symptoms, although the effect size was small (Cohen's d: 0.208).

The study revealed a significant placebo response (Cohen's d: 2.909), indicating that factors like the number of trial arms, study sites, and industry sponsorship can influence the placebo effect, suggesting a need for improved trial designs to accurately assess treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of Placebo Response in Pharmacological Clinical Trials of Negative Symptoms in Schizophrenia: A Meta-regression Analysis. Fraguas, D., Díaz-Caneja, CM., Pina-Camacho, L., et al.[2022]

In a study involving 13 outpatients with chronic but stable schizophrenia, donepezil significantly improved negative symptoms of schizophrenia compared to baseline and placebo, as measured by the Positive and Negative Symptom Scale (PANSS).

The study used a randomized, counterbalanced design over 24 weeks, with participants receiving donepezil at two different doses (5 mg and 10 mg) and a placebo, highlighting the potential of cholinesterase inhibitors as an effective augmentation strategy for managing schizophrenia symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind donepezil-placebo crossover augmentation study of atypical antipsychotics in chronic, stable schizophrenia: a pilot study. Risch, SC., Horner, MD., McGurk, SR., et al.[2018]

A meta-analysis of 92 trials involving 22,645 participants found that long-acting injectable (LAI) and oral antipsychotics significantly prevent relapse in schizophrenia-spectrum disorders, with high confidence in the effectiveness of amisulpride, olanzapine, and aripiprazole.

Both LAI and oral formulations of olanzapine, aripiprazole, and paliperidone are recommended as the best options for maintenance treatment, particularly in resource-limited settings, as they showed the highest efficacy for relapse prevention without significant tolerability issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral and long-acting antipsychotics for relapse prevention in schizophrenia-spectrum disorders: a network meta-analysis of 92 randomized trials including 22,645 participants. Ostuzzi, G., Bertolini, F., Tedeschi, F., et al.[2022]

The study found that both LY379268, an mGlu2/3 receptor agonist, and BINA, an mGlu2 receptor positive allosteric modulator, effectively reduced the immobility time in rats subjected to negative symptoms induced by MK-801, suggesting their potential as treatments for schizophrenia's negative symptoms.

These compounds did not affect immobility in saline-treated rats, indicating their specific action on the negative symptoms of schizophrenia rather than general sedative effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stimulation of the metabotropic glutamate (mGlu) 2 receptor attenuates the MK-801-induced increase in the immobility time in the forced swimming test in rats. Kawaura, K., Karasawa, J., Hikichi, H.[2020]

In a phase 1b study with 37 patients and a phase 2 study involving 240 outpatients, the PDE10A inhibitor PF-02545920 was found to be well tolerated, indicating a good safety profile for this treatment approach.

Despite being well tolerated, PF-02545920 did not show significant efficacy in improving symptoms of schizophrenia compared to placebo, suggesting that PDE10A inhibitors may not be effective as antipsychotic agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Proof-of-Concept Study Evaluating the Phosphodiesterase 10A Inhibitor PF-02545920 in the Adjunctive Treatment of Suboptimally Controlled Symptoms of Schizophrenia. DeMartinis, N., Lopez, RN., Pickering, EH., et al.[2020]

References

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

Predictors of Placebo Response in Pharmacological Clinical Trials of Negative Symptoms in Schizophrenia: A Meta-regression Analysis. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Double-blind donepezil-placebo crossover augmentation study of atypical antipsychotics in chronic, stable schizophrenia: a pilot study. [2018]

3. Italy pubmed.ncbi.nlm.nih.gov

Oral and long-acting antipsychotics for relapse prevention in schizophrenia-spectrum disorders: a network meta-analysis of 92 randomized trials including 22,645 participants. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Stimulation of the metabotropic glutamate (mGlu) 2 receptor attenuates the MK-801-induced increase in the immobility time in the forced swimming test in rats. [2020]

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

A Proof-of-Concept Study Evaluating the Phosphodiesterase 10A Inhibitor PF-02545920 in the Adjunctive Treatment of Suboptimally Controlled Symptoms of Schizophrenia. [2020]