Clinical trial NCT03084783: Dexamethasone in Herpes Simplex Virus Encephalitis
Official title: Dexamethasone in Herpes Simplex Virus Encephalitis Open Label Randomized Controlled Trial With an Observer-blinded Evaluation at 6 Months
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: HSV Encephalitis
Keywords: dexamethasone
HSV encephalitis
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
Collaborators: name: University of Liverpool
First posted: 2017-03-21
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Calcul of verbal memory score
timeFrame: at 6 months post randomization
Secondary outcomes:
measure: Visual Memory Index assessed by the Wechsler Memory Scale
timeFrame: 6 months and 18 months post randomization
measure: Processing Working Memory - assessed by the Wechsler Adult Intelligence Scale version IV
timeFrame: 6 months and 18 months post randomization
measure: Higher executive function -assessed by Trail Making Test Parts A and B
timeFrame: 6 months and 18 months post randomization
measure: Anxiety -assessed by self-completed Beck Anxiety Inventory
timeFrame: 6 months and 18 months post randomization
measure: Depression -assessed by self-completed Beck Depression Inventory Inventory
timeFrame: 6 months and 18 months post randomization
measure: Cognitive Assessment assessed by Addenbrooke's Cognitive Assessment revised (ACE-III)
timeFrame: at 30 days/discharge, 6 and 18 months
measure: Requirement of intensive care or high dependency admission
timeFrame: during 18 months
measure: Time to recovery of Glasgow Coma Scale (GCS)
timeFrame: during 18 months
measure: Incidence of epilepsy
timeFrame: during 18 months
measure: Measurement of temporal lobe volume (as % of intra-cranial volume)
timeFrame: Baseline, 2 weeks, 6 months and 18 months
measure: Measurement of Whole brain volume (as % of intra-cranial volume)
timeFrame: Baseline, 2 weeks, 6 months and 18 months
measure: Transcriptomic and proteomic profiling on CSF
timeFrame: at baseline and 2 weeks
measure: Transcriptomic and proteomic profiling on blood
timeFrame: at baseline, 4 days, 2 weeks, and 6 months
measure: Anti NMDA receptor antibody testing
timeFrame: at 6 months
measure: Proportion of patients with detectable HSV in CSF
timeFrame: at 2 weeks
measure: Health Status Measured by the EuroQOL-5D-5L questionnaire
timeFrame: at 6 and 18 months
measure: Quality of Life measured by SF-36 questionnaires
timeFrame: at 6 and 18 months
Other outcomes:
Locations:
city: Montpellier
country: France
facility: Hôpital Gui de Chauliac
city: Nantes
country: France
facility: CHU Hôtel-Dieu
city: Paris
country: France
facility: Hôpital Bichat-Claude Bernard, APHP
city: Rennes
country: France
facility: CHU Rennes, Hôpital Pontchaillou
city: Rouen
country: France
facility: Hôpital Charles Nicolle
city: Saint-Denis
country: France
facility: Hôpital Delafontaine
city: Strasbourg
country: France
facility: CHU Strasbourg
city: Vandoeuvre Les Nancy
country: France
facility: CHRU de Nancy, Hopitaux de Brabois
Study officials:
affiliation: University Hospital, Grenoble
name: Jean-Paul STAHL
role: PRINCIPAL_INVESTIGATOR
References:
citation: Whitley RJ. Herpes simplex encephalitis: adolescents and adults. Antiviral Res. 2006 Sep;71(2-3):141-8. doi: 10.1016/j.antiviral.2006.04.002. Epub 2006 Apr 25.
citation: Granerod J, Ambrose HE, Davies NW, Clewley JP, Walsh AL, Morgan D, Cunningham R, Zuckerman M, Mutton KJ, Solomon T, Ward KN, Lunn MP, Irani SR, Vincent A, Brown DW, Crowcroft NS; UK Health Protection Agency (HPA) Aetiology of Encephalitis Study Group. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis. 2010 Dec;10(12):835-44. doi: 10.1016/S1473-3099(10)70222-X. Epub 2010 Oct 15.
citation: Tunkel AR, Glaser CA, Bloch KC, Sejvar JJ, Marra CM, Roos KL, Hartman BJ, Kaplan SL, Scheld WM, Whitley RJ; Infectious Diseases Society of America. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2008 Aug 1;47(3):303-27. doi: 10.1086/589747.