Investigating the Effect of Diroximel Fumarate on Glutathione in Schizophrenia
NCT ID: NCT06957808
Last Updated: 2025-05-05
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
NA
30 participants
INTERVENTIONAL
2025-01-10
2026-06-30
Brief Summary
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Detailed Description
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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
Conditions
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Study Design
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RANDOMIZED
SINGLE_GROUP
BASIC_SCIENCE
TRIPLE
Study Groups
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Open label
Participants take the research drug for 14 days in an open label phase.
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.
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.
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.
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.
Placebo
A placebo pill given to participants.
Interventions
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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.
Placebo
A placebo pill given to participants.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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
18 Years
65 Years
ALL
No
Sponsors
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Rosetrees Trust
OTHER
King's College London
OTHER
Responsible Party
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Katherine Beck
Dr
Principal Investigators
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Katherine Beck, Clinical Lecturer
Role: PRINCIPAL_INVESTIGATOR
Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience
Locations
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South London and Maudsley NHS Foundation Trust
London, Greater London, United Kingdom
Department of Computer Science, Faculty of Engineering Science, University College London
London, Greater London, United Kingdom
School of Psychology, University of birmingham
Birmingham, , United Kingdom
Countries
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Central Contacts
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Violeta Perez-Rodriguez, Clinical Research Associate
Role: CONTACT
Facility Contacts
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Violeta Perez-Rodriguez, Clinical Research Associate
Role: primary
References
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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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Related Links
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Study reference
Other Identifiers
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331465
Identifier Type: -
Identifier Source: org_study_id
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