Dexamethasone in Herpes Simplex Virus Encephalitis (DexEnceph)

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

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.

Study Overview

• Status: Unknown
• Conditions: HSV Encephalitis
• Intervention / Treatment: Drug: Dexamethasone

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jean-Paul STAHL, MD; Phone Number: 04 76 76 68 13; Email: jpstahl@chu-grenoble.fr
• Study Contact Backup: Name: Saber TOUATI, PhD; Email: stouati1@chu-grenoble.fr

Study Locations

• France
  • Montpellier, France, 34295
    • Recruiting
    • Hopital Gui de Chauliac
    • Principal Investigator: LE MOING, MD, PhD
  • Nantes, France, 44093
    • Recruiting
    • CHU Hôtel-Dieu
    • Principal Investigator: BOUTOILLE
  • Paris, France, 75877
    • Recruiting
    • Hôpital Bichat-Claude Bernard, APHP
    • Principal Investigator: Romain SONNEVILLE, MD, PhD
  • Rennes, France, 35000
    • Recruiting
    • CHU Rennes, Hôpital Pontchaillou
    • Principal Investigator: Pierre TATTEVIN, MD, PhD
  • Rouen, France, 76031
    • Recruiting
    • Hopital Charles Nicolle
    • Principal Investigator: Isabelle GUEIT, MD, PhD
  • Saint-Denis, France, 93205
    • Recruiting
    • Hôpital Delafontaine
    • Principal Investigator: DE BROUCKER, MD, PhD
  • Strasbourg, France, 67091
    • Recruiting
    • CHU Strasbourg
    • Principal Investigator: Yvon RUCH, MD
  • Vandoeuvre Les Nancy, France, 54511
    • Recruiting
    • CHRU de Nancy, Hopitaux de Brabois
    • Principal Investigator: Céline PULCINI, Md, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble
• Collaborators: University of Liverpool
• Investigators: Principal Investigator: Jean-Paul STAHL, University Hospital, Grenoble

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Anticipated): November 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: February 3, 2017
• First Submitted That Met QC Criteria: March 14, 2017
• First Posted (Actual): March 21, 2017

Study Record Updates

• Last Update Posted (Actual): September 4, 2020
• Last Update Submitted That Met QC Criteria: September 3, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: dexamethasone; HSV encephalitis
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Virus Diseases; Infections; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infectious Encephalitis; DNA Virus Infections; Skin Diseases, Infectious; Skin Diseases, Viral; Herpesviridae Infections; Encephalitis; Herpes Simplex; Encephalitis, Herpes Simplex; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: 38RC16.015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No