Dexamethasone in Herpes Simplex Virus Encephalitis

Study Overview
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Brief Summary
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Encephalitics is a serious condition in which the brain becomes inflamed (swollen). It usually happens as a direct result of virus, such as herpes simplex virus (HSV). HSV encephalitis is often treated with the drug acyclovir (an antiviral drug which slows the growth and spread of HSV in the body). Despite this however, around 2 out of every 3 people will have memory difficulties long term. Dexamethasone is a corticosteroid medication, which works by preventing the release of natural chemicals in the body which cause inflammation. It is possible that dexamethasone could help to reduce in swelling of the brain may improve the recovery of patients with HSV encephalitis. The aim of this study is to find out whether treatment with dexamethasone can improve long-term health outcomes in adults with HSV Encephalitis.

Official Title
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Dexamethasone in Herpes Simplex Virus Encephalitis Open Label Randomized Controlled Trial With an Observer-blinded Evaluation at 6 Months

Conditions
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HSV Encephalitis

Intervention / Treatment
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* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Suspected encephalitis criteria: Acute or subacute (up to 4 weeks) alteration in consciousness, cognition, personality or behaviour* persisting for > 24 hours Laboratory confirmed HSV by positive PCR on CSF sample. Receiving intravenous aciclovir dosed at 10mg/kg TDS or at a reduced dose in renal impairment Age ≥ 18 years Person affiliated to social security Written informed consent has been given by the patient or their legal representative Exclusion Criteria: Currently receiving oral or injectable corticosteroid therapy; including treatment with oral or injectable corticosteroids in the last 30 days. History of hypersensitivity to corticosteroids Immunosuppression secondary to: Known HIV infection & CD4 count under 200cell/mm3 Biologic therapy or other immunosuppressive agents [azathioprine, methotrexate, ciclosporin] Solid organ transplant on immunosuppression Bone marrow transplant Currently undergoing a course of chemotherapy or radiotherapy Known immunodeficiency syndrome [other than HIV] Known haematological malignancy Pre-existing indwelling ventricular devices Peptic ulcer disease in the last 6 months: defined as a peptic ulcer seen at previous endoscopy or an upper gastrointestinal bleed causing ≥ 2 unit haemoglobin drop Currently on an antiretroviral regime containing rilpivirine Patients under legal protection, administrative or judicial control Pregnancy / Breast feeding and parturient Subject in exclusion period of another study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>Participants receive dexamethasone 10mg intravenously 6 hourly for 4 days. | Drug: Dexamethasone<br>* Participants receive dexamethasone 10mg intravenously 6 hourly for 4 days.<br>|
| No Intervention: Control group<br>Participants receive standard care and no dexamethasone. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Calcul of verbal memory score | The primary outcome is a verbal memory score as determined by the Wechsler Memory Scale (WMS-IV) Auditory Memory Index, at 6 months post randomisation. | at 6 months post randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Memory Index assessed by the Wechsler Memory Scale | Neuropsychological outcome | 6 months and 18 months post randomization | 
| Processing Working Memory - assessed by the Wechsler Adult Intelligence Scale version IV | Neuropsychological outcome | 6 months and 18 months post randomization | 
| Higher executive function -assessed by Trail Making Test Parts A and B | Neuropsychological outcome | 6 months and 18 months post randomization | 
| Anxiety -assessed by self-completed Beck Anxiety Inventory | Neuropsychological outcome | 6 months and 18 months post randomization | 
| Depression -assessed by self-completed Beck Depression Inventory Inventory | Neuropsychological outcome | 6 months and 18 months post randomization | 
| Cognitive Assessment assessed by Addenbrooke's Cognitive Assessment revised (ACE-III) |  | at 30 days/discharge, 6 and 18 months | 
| Requirement of intensive care or high dependency admission | clinical outcome | during 18 months | 
| Time to recovery of Glasgow Coma Scale (GCS) | clinical outcome | during 18 months | 
| Incidence of epilepsy | clinical outcome | during 18 months | 
| Measurement of temporal lobe volume (as % of intra-cranial volume) | Imaging Outcomes | Baseline, 2 weeks, 6 months and 18 months | 
| Measurement of Whole brain volume (as % of intra-cranial volume) | Imaging Outcomes | Baseline, 2 weeks, 6 months and 18 months | 
| Transcriptomic and proteomic profiling on CSF | Biomarker outcomes | at baseline and 2 weeks | 
| Transcriptomic and proteomic profiling on blood | Biomarker outcome | at baseline, 4 days, 2 weeks, and 6 months | 
| Anti NMDA receptor antibody testing | Biomarker outcome | at 6 months | 
| Proportion of patients with detectable HSV in CSF | Safety Outcome | at 2 weeks | 
| Health Status Measured by the EuroQOL-5D-5L questionnaire |  | at 6 and 18 months | 
| Quality of Life measured by SF-36 questionnaires |  | at 6 and 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dexamethasone, HSV encephalitis