Investigating the Effect of Diroximel Fumarate on Glutathione in Schizophrenia

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

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