Investigating the Effect of Diroximel Fumarate on Glutathione in Schizophrenia

Last updated: May 2, 2025
Sponsor: King's College London
Overall Status: Active - Recruiting

Phase

N/A

Condition

Mood Disorders

Schizotypal Personality Disorder (Spd)

Psychosis

Treatment

Diroximel fumarate (DRF)

Placebo

Clinical Study ID

NCT06957808
331465
  • Ages 18-65
  • All Genders

Study Summary

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 we 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. They 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), we 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • 18 -65 years, diagnosis of schizophrenia (Diagnostic and Statistical Manual ofMental 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 studyenrolment

  • Minimum of 60 on the Positive and Negative Syndrome Scale (PANSS)

  • Capacity to provide informed consent

Exclusion

Exclusion Criteria:

  • History of significant co-morbid medical or neurological disorder including but notlimited to HIV, malignancies, Systemic Lupus Erythematosus, sarcoidosis, autoimmunevasculitis, bone marrow transplantation

  • Current use of medication that is known to interact with DRF, live vaccines givenwithin the period of DRF treatment, nephrotoxic medication (including but notlimited to aminoglycosides, diuretics, non-steroidal anti-inflammatory drugs,Lithium)

  • Contraindications to DRF (pregnancy, women of childbearing potential not currentlyusing effective contraception (combined pill (oestrogen & progesterone),progesterone -only with inhibition of ovulation, intrauterine device, intrauterinehormone-releasing system, bilateral tubal occlusion, vasectomised partner, sexualabstinence), breast feeding, severe hepatic impairment, moderate renal impairment,severe active gastrointestinal disease, lymphocyte count - below the Lower Limit ofNormal (LLN) for the local laboratory (e.g 1.30 x109/L LLN for Viapath King'sCollege London), suspected or confirmed progressive multifocal leukoencephalopathy (PML), presence of risk factors for PML (previous and/or current immunosuppressantor immunomodulatory treatment (including natalizumab, other fumaric esters includingDimethyl Fumarate (DMF) (topical or systemic)), serious infection, current or recentherpes virus infection)

  • Substance dependence/abuse other than to cigarettes

  • Current high suicide risk

  • Participation in a clinical study of unlicensed medicines within the previous 30days

  • Presence/history of other acute or chronic illness that would make participatingunsafe 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 30days

Study Design

Total Participants: 30
Treatment Group(s): 2
Primary Treatment: Diroximel fumarate (DRF)
Phase:
Study Start date:
January 10, 2025
Estimated Completion Date:
June 30, 2026

Study 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 they will have the option to participate in the second phase of the study, where they 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

Connect with a study center

  • Department of Computer Science, Faculty of Engineering Science, University College London

    London, Greater London WC1E 6BT
    United Kingdom

    Active - Recruiting

  • South London and Maudsley NHS Foundation Trust

    London, Greater London SE58AZ
    United Kingdom

    Active - Recruiting

  • School of Psychology, University of birmingham

    Birmingham, B15 2TT
    United Kingdom

    Active - Recruiting

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