Investigating the Effect of Diroximel Fumarate on Glutathione in Schizophrenia (FORTUNE)

February 11, 2026 updated by: Katherine Beck, King's College London
Schizophrenia is a condition that causes symptoms like delusions, hallucinations, reduced motivation and muddled thinking. It is a common, severe and disabling psychiatric illness affecting about 1/100 (1%) of people. It is ranked the third most disabling illness worldwide. Six in seven patients do not recover from the illness in 6-12 months and continue to experience psychotic symptoms. Therefore, there is a strong unmet need for new evidence-based treatments to target the neurobiology underlying schizophrenia. There is increasing evidence to indicate that glutathione (GSH), the main brain antioxidant, is abnormal in schizophrenia and may provide a new treatment target. In this study, the investigators plan to determine whether Diroximel Fumarate (DRF) (currently a treatment for a brain disorder called multiple sclerosis) can increase GSH in the brain of patients with schizophrenia using a brain scan (MRI) and explore whether changes in GSH are related to other brain measures (measured with MRI and EEG- which measures electrical activity in the brain), blood markers of GSH, and symptoms. During this study 30 people with schizophrenia will be recruited. Participants will take the drug DRF for two weeks, a computer will then decide randomly whether each person will continue to take DRF or a placebo/dummy pill for another two weeks. During this part of the study neither the patients nor the researchers will know which type of drug the patient is taking. Brain GSH and the other measures described will be assessed before and after taking the DRF and placebo/dummy pill. At the end of the study (2027), the investigators will see if taking DRF alters the brain chemical (GSH) in people with schizophrenia and whether this is linked to other measures and symptoms. It will also give researchers information about the best way to design future studies for patients with schizophrenia using this drug.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Study Objectives: To determine if the level of GSH in the ACC, as indexed by 1HMRS, will increase after treatment with DRF compared to baseline in patients with schizophrenia.

Study Design: Participants will take DRF as open label for 2 weeks (231mg for 7 days, then increase to 462mg for another 7 days), then participants will have the option to participate in the second phase of the study, where participants will be randomly allocated to either DRF for further 2 weeks or placebo. Allocation will be double-blinded. Participants will have baseline blood tests, schizophrenia rating scales, EEG and MRI, and these will be repeated after the open label and once again after the randomised phase.

30 patients with schizophrenia will be recruited from mental health teams.

Inclusion Criteria:

  • 18-65 years
  • diagnosis of schizophrenia (Diagnostic and Statistical Manual of Mental Disorders-5 (SCID) (DSM-5)
  • stable antipsychotic dose (no change for 1 month)
  • currently stable in mental state with no evidence of relapse within the last 2 months prior to study enrolment
  • minimum score of 60 Positive and Negative Syndrome Scale (PANSS)
  • capacity to provide informed consent

Exclusion criteria (https://www.medicines.org.uk/emc/product/13087/smpc):

  • history of significant co-morbid medical or neurological disorder including but not limited to HIV, malignancies, Systemic Lupus Erythematosus, sarcoidosis, autoimmune vasculitis, bone marrow transplantation
  • current use of medication that is known to interact with DRF, live vaccines given within the period of DRF treatment, nephrotoxic medication (including but not limited to aminoglycosides, diuretics, non-steroidal anti-inflammatory drugs, Lithium)
  • contraindications to DRF (pregnancy, women of childbearing potential not currently using effective contraception (combined pill (oestrogen & progesterone), progesterone -only with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner, sexual abstinence), breast feeding, severe hepatic impairment, moderate renal impairment, severe active gastrointestinal disease, lymphocyte count - below the Lower Limit of Normal (LLN) for the local laboratory (e.g 1.30 x109/L LLN for Viapath Kings College London), suspected or confirmed progressive multifocal leukoencephalopathy (PML), presence of risk factors for PML (previous and/or current immunosuppressant or immunomodulatory treatment (including natalizumab, other fumaric esters including Dimethyl Fumarate (DMF) (topical or systemic)), serious infection, current or recent herpes virus infection)
  • substance dependence/abuse other than to cigarettes
  • current high suicide risk
  • participation in a clinical study of unlicensed medicines within the previous 30 days
  • presence/history of other acute or chronic illness that would make participating unsafe or unsuitable, any contraindication to MRI scanning (e.g. claustrophobia, metallic implants, pacemaker, vascular clips, metal in eyes, pregnancy)
  • allergies to any of DRFs ingredients
  • taking part in a research study involving an unlicensed medicine within the last 30 days

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United Kingdom
      • Birmingham, United Kingdom, B15 2TT
        • Recruiting
        • School of Psychology, University of birmingham
        • Contact:
        • Principal Investigator:
          • Rachel Upthegrove, Professor
    • Greater London
      • London, Greater London, United Kingdom, SE58AZ
        • Recruiting
        • South London and Maudsley NHS Foundation Trust
        • Contact:
        • Contact:
        • Principal Investigator:
          • Katherine Beck, Clinical Lecturer
        • Sub-Investigator:
          • Violeta Perez-Rodriguez, Clinical Research Associate
        • Sub-Investigator:
          • Zeryab Meyer, Clinical Research Associate
        • Sub-Investigator:
          • Oliver Howes, Professor
        • Sub-Investigator:
          • Mitul Mehta, Professor
        • Sub-Investigator:
          • David Lythgoe, Senior Research Fellow
      • London, Greater London, United Kingdom, WC1E 6BT
        • Recruiting
        • Department of Computer Science, Faculty of Engineering Science, University College London
        • Contact:
        • Principal Investigator:
          • Rick Adams, Professor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 18 -65 years, diagnosis of schizophrenia (Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5)
  • Stable antipsychotic dose (no change for 1 month)
  • Currently stable with no evidence of relapse within the last 2 months prior to study enrolment
  • Minimum of 60 on the Positive and Negative Syndrome Scale (PANSS)
  • Capacity to provide informed consent

Exclusion Criteria:

  • History of significant co-morbid medical or neurological disorder including but not limited to HIV, malignancies, Systemic Lupus Erythematosus, sarcoidosis, autoimmune vasculitis, bone marrow transplantation
  • Current use of medication that is known to interact with DRF, live vaccines given within the period of DRF treatment, nephrotoxic medication (including but not limited to aminoglycosides, diuretics, non-steroidal anti-inflammatory drugs, Lithium)
  • Contraindications to DRF (pregnancy, women of childbearing potential not currently using effective contraception (combined pill (oestrogen & progesterone), progesterone -only with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner, sexual abstinence), breast feeding, severe hepatic impairment, moderate renal impairment, severe active gastrointestinal disease, lymphocyte count - below the Lower Limit of Normal (LLN) for the local laboratory (e.g 1.30 x109/L LLN for Viapath King's College London), suspected or confirmed progressive multifocal leukoencephalopathy (PML), presence of risk factors for PML (previous and/or current immunosuppressant or immunomodulatory treatment (including natalizumab, other fumaric esters including Dimethyl Fumarate (DMF) (topical or systemic)), serious infection, current or recent herpes virus infection)
  • Substance dependence/abuse other than to cigarettes
  • Current high suicide risk
  • Participation in a clinical study of unlicensed medicines within the previous 30 days
  • Presence/history of other acute or chronic illness that would make participating unsafe or unsuitable, any contraindication to MRI scanning (e.g. claustrophobia, metallic implants, pacemaker, vascular clips, metal in eyes, pregnancy)
  • Allergies to any of DRFs ingredients
  • Taking part in a research study involving an unlicensed medicine within the last 30 days

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Open label
Participants take the research drug for 14 days in an open label phase.
Drug: Diroximel fumarate (DRF)
Diroximel fumarate is an immunomodulating drug licensed for use in multiple sclerosis. It has been found to cross the blood brain barrier and increase brain glutathione levels.
Other Names:
  • Vumerity
Active Comparator: Double-blind - DRF
After open label phase, participants can be randomised to either the research drug (diroximel fumarate, DRF) or placebo for a further 2 weeks.
Drug: Diroximel fumarate (DRF)
Diroximel fumarate is an immunomodulating drug licensed for use in multiple sclerosis. It has been found to cross the blood brain barrier and increase brain glutathione levels.
Other Names:
  • Vumerity
Placebo Comparator: Double blind - Placebo
After open label phase, participants can be randomised to either the research drug (diroximel fumarate, DRF) or placebo for a further 2 weeks.
Drug: Placebo
A placebo pill given to participants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
MRS glutathione (GSH) levels in ACC
Time Frame: Within one year of conclusion of the Research
Glutathione levels in the Anterior Cingulate Cortex (ACC) measured by magnetic resonance spectroscopy (1HMRS)
Within one year of conclusion of the Research

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
MMN Amplitude
Time Frame: Within one year of conclusion of the Research
Mismatch negativity Amplitude measured by electroencephalography (EEG)
Within one year of conclusion of the Research

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

King's College London

Collaborators

South London and Maudsley NHS Foundation Trust
Rosetrees Trust

Investigators

  • Principal Investigator: Katherine Beck, Clinical Lecturer, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 10, 2025

Primary Completion (Estimated)

January 20, 2027

Study Completion (Estimated)

January 20, 2027

Study Registration Dates

First Submitted

May 2, 2025

First Submitted That Met QC Criteria

May 2, 2025

First Posted (Actual)

May 5, 2025

Study Record Updates

Last Update Posted (Actual)

February 13, 2026

Last Update Submitted That Met QC Criteria

February 11, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 331465

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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