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Dexamethasone in Herpes Simplex Virus Encephalitis (DexEnceph)

Primary Purpose

HSV Encephalitis

Status
Unknown status
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Dexamethasone
Sponsored by
University Hospital, Grenoble
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HSV Encephalitis focused on measuring dexamethasone, HSV encephalitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hôpital Gui de ChauliacRecruiting
  • CHU Hôtel-DieuRecruiting
  • Hôpital Bichat-Claude Bernard, APHPRecruiting
  • CHU Rennes, Hôpital PontchaillouRecruiting
  • Hôpital Charles NicolleRecruiting
  • Hôpital DelafontaineRecruiting
  • CHU StrasbourgRecruiting
  • CHRU de Nancy, Hopitaux de BraboisRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Intervention group

Control group

Arm Description

Participants receive dexamethasone 10mg intravenously 6 hourly for 4 days.

Participants receive standard care and no dexamethasone.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
February 3, 2017
Last Updated
September 3, 2020
Sponsor
University Hospital, Grenoble
Collaborators
University of Liverpool
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1. Study Identification

Unique Protocol Identification Number
NCT03084783
Brief Title
Dexamethasone in Herpes Simplex Virus Encephalitis
Acronym
DexEnceph
Official Title
Dexamethasone in Herpes Simplex Virus Encephalitis Open Label Randomized Controlled Trial With an Observer-blinded Evaluation at 6 Months
Study Type
Interventional

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Unknown status
Study Start Date
November 1, 2018 (Actual)
Primary Completion Date
November 1, 2020 (Anticipated)
Study Completion Date
December 1, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Grenoble
Collaborators
University of Liverpool

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HSV Encephalitis
Keywords
dexamethasone, HSV encephalitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intervention group
Arm Type
Experimental
Arm Description
Participants receive dexamethasone 10mg intravenously 6 hourly for 4 days.
Arm Title
Control group
Arm Type
No Intervention
Arm Description
Participants receive standard care and no dexamethasone.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Participants receive dexamethasone 10mg intravenously 6 hourly for 4 days.
Primary Outcome Measure Information:
Title
Calcul of verbal memory score
Description
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.
Time Frame
at 6 months post randomization
Secondary Outcome Measure Information:
Title
Visual Memory Index assessed by the Wechsler Memory Scale
Description
Neuropsychological outcome
Time Frame
6 months and 18 months post randomization
Title
Processing Working Memory - assessed by the Wechsler Adult Intelligence Scale version IV
Description
Neuropsychological outcome
Time Frame
6 months and 18 months post randomization
Title
Higher executive function -assessed by Trail Making Test Parts A and B
Description
Neuropsychological outcome
Time Frame
6 months and 18 months post randomization
Title
Anxiety -assessed by self-completed Beck Anxiety Inventory
Description
Neuropsychological outcome
Time Frame
6 months and 18 months post randomization
Title
Depression -assessed by self-completed Beck Depression Inventory Inventory
Description
Neuropsychological outcome
Time Frame
6 months and 18 months post randomization
Title
Cognitive Assessment assessed by Addenbrooke's Cognitive Assessment revised (ACE-III)
Time Frame
at 30 days/discharge, 6 and 18 months
Title
Requirement of intensive care or high dependency admission
Description
clinical outcome
Time Frame
during 18 months
Title
Time to recovery of Glasgow Coma Scale (GCS)
Description
clinical outcome
Time Frame
during 18 months
Title
Incidence of epilepsy
Description
clinical outcome
Time Frame
during 18 months
Title
Measurement of temporal lobe volume (as % of intra-cranial volume)
Description
Imaging Outcomes
Time Frame
Baseline, 2 weeks, 6 months and 18 months
Title
Measurement of Whole brain volume (as % of intra-cranial volume)
Description
Imaging Outcomes
Time Frame
Baseline, 2 weeks, 6 months and 18 months
Title
Transcriptomic and proteomic profiling on CSF
Description
Biomarker outcomes
Time Frame
at baseline and 2 weeks
Title
Transcriptomic and proteomic profiling on blood
Description
Biomarker outcome
Time Frame
at baseline, 4 days, 2 weeks, and 6 months
Title
Anti NMDA receptor antibody testing
Description
Biomarker outcome
Time Frame
at 6 months
Title
Proportion of patients with detectable HSV in CSF
Description
Safety Outcome
Time Frame
at 2 weeks
Title
Health Status Measured by the EuroQOL-5D-5L questionnaire
Time Frame
at 6 and 18 months
Title
Quality of Life measured by SF-36 questionnaires
Time Frame
at 6 and 18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jean-Paul STAHL, MD
Phone
04 76 76 68 13
Email
jpstahl@chu-grenoble.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Saber TOUATI, PhD
Email
stouati1@chu-grenoble.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean-Paul STAHL
Organizational Affiliation
University Hospital, Grenoble
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Gui de Chauliac
City
Montpellier
ZIP/Postal Code
34295
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
LE MOING, MD, PhD
Facility Name
CHU Hôtel-Dieu
City
Nantes
ZIP/Postal Code
44093
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
BOUTOILLE
Facility Name
Hôpital Bichat-Claude Bernard, APHP
City
Paris
ZIP/Postal Code
75877
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Romain SONNEVILLE, MD, PhD
Facility Name
CHU Rennes, Hôpital Pontchaillou
City
Rennes
ZIP/Postal Code
35000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pierre TATTEVIN, MD, PhD
Facility Name
Hôpital Charles Nicolle
City
Rouen
ZIP/Postal Code
76031
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Isabelle GUEIT, MD, PhD
Facility Name
Hôpital Delafontaine
City
Saint-Denis
ZIP/Postal Code
93205
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
DE BROUCKER, MD, PhD
Facility Name
CHU Strasbourg
City
Strasbourg
ZIP/Postal Code
67091
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yvon RUCH, MD
Facility Name
CHRU de Nancy, Hopitaux de Brabois
City
Vandoeuvre Les Nancy
ZIP/Postal Code
54511
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Céline PULCINI, Md, PhD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
16675036
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.
Results Reference
background
PubMed Identifier
20952256
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. Erratum In: Lancet Infect Dis. 2011 Feb;11(2):79.
Results Reference
background
PubMed Identifier
18582201
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.
Results Reference
background

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Dexamethasone in Herpes Simplex Virus Encephalitis

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