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Schizophrenia DisordersFORTUNENCT06957808

Investigating the Effect of Diroximel Fumarate on Glutathione in Schizophrenia

A study testing Diroximel fumarate (DRF) in people with Schizophrenia Disorders, run by King's College London at 3 sites in United Kingdom.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Schizophrenia Disorders
What is being tested?
Diroximel fumarate (DRF)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
30 participants
Where
3 sitesUnited Kingdom
Study dates
10 Jan 2025to 20 Jan 2027
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 9Show fewer
  • 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

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Violeta Perez-Rodriguez, Clinical Research Associate contact

(+44)07871777185

violeta.perez_rodriguez@kcl.ac.uk

Zeryab Meyer, Clinical Research Associate contact

zeryab.meyer@kcl.ac.uk

United Kingdom3 sites, 3 recruiting
  • School of Psychology, University of birmingham

    Birmingham, B15 2TT

    Rachel Upthegrove, Professor, r.upthegrove@bham.ac.uk

    Rachel Upthegrove, Professor

    Recruiting
  • South London and Maudsley NHS Foundation Trust

    London, Greater London, SE58AZ

    Violeta Perez-Rodriguez, Clinical Research Associate, (+44)07871777185, violeta.perez_rodriguez@kcl.ac.uk

    Zeryab Meyer, Clinical Research Associate, zeryab.meyer@kcl.ac.uk

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

    London, Greater London, WC1E 6BT

    Rick Adams, Professor, rick.adams@ucl.ac.uk

    Rick Adams, Professor

    Recruiting

Other trials in United Kingdom

About this study

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.

Read the 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
Being tested
Diroximel fumarate (DRF), Placebo
Keywords
psychosis, schizophrenia, inflammation, diroximel fumarate, neuroimaging, antioxidant, glutathione
Medical subject headings
Schizophrenia, Psychotic Disorders, Inflammation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Diroximel fumarate (DRF)Drug

    Also called Vumerity

    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.

  • PlaceboDrug

    A placebo pill given to participants.

Study groups in NCT06957808
Study groupRoleWhat they receive
Open labelExperimentalParticipants take the research drug for 14 days in an open label phase.
Receives: Drug: Diroximel fumarate (DRF)
Double-blind - DRFActive comparatorAfter open label phase, participants can be randomised to either the research drug (diroximel fumarate, DRF) or placebo for a further 2 weeks.
Receives: Drug: Diroximel fumarate (DRF)
Double blind - PlaceboPlacebo comparatorAfter open label phase, participants can be randomised to either the research drug (diroximel fumarate, DRF) or placebo for a further 2 weeks.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. MRS glutathione (GSH) levels in ACC

    Glutathione levels in the Anterior Cingulate Cortex (ACC) measured by magnetic resonance spectroscopy (1HMRS)

    Measured: Within one year of conclusion of the Research

Secondary outcomes (1)
  1. MMN Amplitude

    Mismatch negativity Amplitude measured by electroencephalography (EEG)

    Measured: Within one year of conclusion of the Research

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 May 2025
  2. Study start10 Jan 2025
  3. Primary completion20 Jan 2027 (estimated)
  4. Study completion20 Jan 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Crossover
Model description
Open label for 2 weeks then randomised to placebo or active drug for further 2 weeks
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06957808
Sponsor's protocol ID
331465
Acronym
FORTUNE
Status last verified
Feb 2026
First submitted
2 May 2025
Last updated
13 Feb 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Gawryluk JW, Wang JF, Andreazza AC, Shao L, Young LT. Decreased levels of glutathione, the major brain antioxidant, in post-mortem prefrontal cortex from patients with psychiatric disorders. Int J Neuropsychopharmacol. 2011 Feb;14(1):123-30. doi: 10.1017/S1461145710000805. Epub 2010 Jul 16.

    PubMed 20633320
  • Ustun TB, Rehm J, Chatterji S, Saxena S, Trotter R, Room R, Bickenbach J. Multiple-informant ranking of the disabling effects of different health conditions in 14 countries. WHO/NIH Joint Project CAR Study Group. Lancet. 1999 Jul 10;354(9173):111-5. doi: 10.1016/s0140-6736(98)07507-2.

    PubMed 10408486
  • Raffa M, Mechri A, Othman LB, Fendri C, Gaha L, Kerkeni A. Decreased glutathione levels and antioxidant enzyme activities in untreated and treated schizophrenic patients. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Oct 1;33(7):1178-83. doi: 10.1016/j.pnpbp.2009.06.018. Epub 2009 Jul 2.

    PubMed 19576938
  • Owjfard M, Karimi F, Mallahzadeh A, Nabavizadeh SA, Namavar MR, Saadi MI, Hooshmandi E, Salehi MS, Zafarmand SS, Bayat M, Karimlou S, Borhani-Haghighi A. Mechanism of action and therapeutic potential of dimethyl fumarate in ischemic stroke. J Neurosci Res. 2023 Sep;101(9):1433-1446. doi: 10.1002/jnr.25202. Epub 2023 May 14.

    PubMed 37183360
  • Linker RA, Lee DH, Ryan S, van Dam AM, Conrad R, Bista P, Zeng W, Hronowsky X, Buko A, Chollate S, Ellrichmann G, Bruck W, Dawson K, Goelz S, Wiese S, Scannevin RH, Lukashev M, Gold R. Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway. Brain. 2011 Mar;134(Pt 3):678-92. doi: 10.1093/brain/awq386.

    PubMed 21354971
  • Jauhar S, Veronese M, Nour MM, Rogdaki M, Hathway P, Turkheimer FE, Stone J, Egerton A, McGuire P, Kapur S, Howes OD. Determinants of treatment response in first-episode psychosis: an 18F-DOPA PET study. Mol Psychiatry. 2019 Oct;24(10):1502-1512. doi: 10.1038/s41380-018-0042-4. Epub 2018 Apr 20.

    PubMed 29679071
  • Jaaskelainen E, Juola P, Hirvonen N, McGrath JJ, Saha S, Isohanni M, Veijola J, Miettunen J. A systematic review and meta-analysis of recovery in schizophrenia. Schizophr Bull. 2013 Nov;39(6):1296-306. doi: 10.1093/schbul/sbs130. Epub 2012 Nov 20.

    PubMed 23172003
  • Halstead S, Siskind D, Amft M, Wagner E, Yakimov V, Shih-Jung Liu Z, Walder K, Warren N. Alteration patterns of peripheral concentrations of cytokines and associated inflammatory proteins in acute and chronic stages of schizophrenia: a systematic review and network meta-analysis. Lancet Psychiatry. 2023 Apr;10(4):260-271. doi: 10.1016/S2215-0366(23)00025-1. Epub 2023 Feb 27.

    PubMed 36863384
  • Gysin R, Kraftsik R, Sandell J, Bovet P, Chappuis C, Conus P, Deppen P, Preisig M, Ruiz V, Steullet P, Tosic M, Werge T, Cuenod M, Do KQ. Impaired glutathione synthesis in schizophrenia: convergent genetic and functional evidence. Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16621-6. doi: 10.1073/pnas.0706778104. Epub 2007 Oct 5.

    PubMed 17921251
  • Gold R, Arnold DL, Bar-Or A, Fox RJ, Kappos L, Mokliatchouk O, Jiang X, Lyons J, Kapadia S, Miller C. Long-term safety and efficacy of dimethyl fumarate for up to 13 years in patients with relapsing-remitting multiple sclerosis: Final ENDORSE study results. Mult Scler. 2022 Apr;28(5):801-816. doi: 10.1177/13524585211037909. Epub 2021 Sep 1.

    PubMed 34465252
  • Do KQ, Trabesinger AH, Kirsten-Kruger M, Lauer CJ, Dydak U, Hell D, Holsboer F, Boesiger P, Cuenod M. Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo. Eur J Neurosci. 2000 Oct;12(10):3721-8. doi: 10.1046/j.1460-9568.2000.00229.x.

    PubMed 11029642
  • Do KQ, Cabungcal JH, Frank A, Steullet P, Cuenod M. Redox dysregulation, neurodevelopment, and schizophrenia. Curr Opin Neurobiol. 2009 Apr;19(2):220-30. doi: 10.1016/j.conb.2009.05.001. Epub 2009 May 27.

    PubMed 19481443
  • Burgdorf JS, Christian EP, Sorensen L, Stanton PK, Leaderbrand K, Madsen TM, Khan MA, Kroes RA, Moskal JR. A translational EEG-based approach to assess modulation of long-lasting NMDAR-dependent synaptic plasticity. Psychopharmacology (Berl). 2019 Dec;236(12):3687-3693. doi: 10.1007/s00213-019-05341-w. Epub 2019 Aug 7.

    PubMed 31392357

Questions about this trial

What is this clinical trial studying?

A study testing Diroximel fumarate (DRF) in people with Schizophrenia Disorders, run by King's College London at 3 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 13 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Violeta Perez-Rodriguez, Clinical Research Associate ((+44)07871777185, violeta.perez_rodriguez@kcl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

MRS glutathione (GSH) levels in ACC (time frame: Within one year of conclusion of the Research). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06957808, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2026.

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