Dexamethasone in Herpes Simplex Virus Encephalitis

HSV Encephalitis Clinical Trial

— DexEnceph  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03084783
• Other study ID #: 38RC16.015
• Status: Recruiting
• Phase: Phase 3
• Start date: November 1, 2018
• Est. completion date: December 1, 2020

Study information

• Verified date: September 2020
• Source: University Hospital, Grenoble
• Contact: Jean-Paul STAHL, MD
• Phone: 04 76 76 68 13
• Email: jpstahl[@]chu-grenoble.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 1, 2020
• Est. primary completion date: November 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Encephalitis
• Herpes Simplex
• HSV Encephalitis

Intervention

Drug:
• Dexamethasone
Participants receive dexamethasone 10mg intravenously 6 hourly for 4 days.

Locations

Country	Name	City	State
France	Hôpital Gui de Chauliac	Montpellier
France	CHU Hôtel-Dieu	Nantes
France	Hôpital Bichat-Claude Bernard, APHP	Paris
France	CHU Rennes, Hôpital Pontchaillou	Rennes
France	Hôpital Charles Nicolle	Rouen
France	Hôpital Delafontaine	Saint-Denis
France	CHU Strasbourg	Strasbourg
France	CHRU de Nancy, Hopitaux de Brabois	Vandoeuvre Les Nancy

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Grenoble	University of Liverpool

Country where clinical trial is conducted

France, 

References & Publications (3)

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. Erratum in: Lancet Infect Dis. 2011 Feb;11(2):79. — View 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. — View Citation

Whitley RJ. Herpes simplex encephalitis: adolescents and adults. Antiviral Res. 2006 Sep;71(2-3):141-8. Epub 2006 Apr 25. Review. — View Citation

Outcome

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