Safety and Efficacy Study of Intravenous Immunoglobulin to Treat Japanese Encephalitis

Summary

Japanese encephalitis is caused by a viral infection of the brain transmitted by the bite of an infected mosquito. Patients with Japanese encephalitis can rapidly develop worsening conscious level and seizures. Around a third will die from the infection and half of survivors have serious long-term neurological disability. The majority of those affected are children. There are many causes of viral encephalitis, however Japanese encephalitis virus is the most common cause worldwide with over 60,000 cases annually. It occurs over much of Asia and the geographical range is expanding. There is no specific treatment for Japanese encephalitis virus, although several have been trialed. In this study we examined the effect of a new treatment, called intravenous immunoglobulin, on children with Japanese encephalitis in Nepal. Prior studies have suggested intravenous immunoglobulin may neutralize Japanese encephalitis virus and suppress damaging inflammation in the brain. It has previously been used in individual cases but never examined in a randomized trial. There was recently a trial of IVIG in West Nile encephalitis in the United States, in which Professor Solomon was on the Scientific Advisory Committee. In this study we will look if intravenous immunoglobulin is safe in this context, and that this treatment may alter the way the immune system manages the infection. Therefore, in this pilot study we will test the hypothesis that IVIG can be safely given to children with suspected JE, with no increased risk of serious adverse events compared with placebo. The aim of this proposal is to conduct a pilot safety and tolerability randomized placebo controlled trial of intravenous immunoglobulin (IVIG) in patients with Japanese encephalitis, to explore the relationship between JEV viral load, pro-inflammatory markers called cytokines and blood brain barrier markers, and the effect of IVIG on these relationships.

Conditions

• Japanese Encephalitis

Interventions

DRUG

Intravenous immunoglobulin [ImmunoRel™ (batch 20081217)]

IVIG group received 400mg/kg/day intravenous at the rate of 0.01 to 0.02 ml/kg body weight/minute for 5 days or appearance of side effect or adverse events. Placebo group received 0.9% saline intravenous at similar rate.

Sponsors & Collaborators

• Kanti Children's Hospital

  collaborator OTHER

• B.P. Koirala Institute of Health Sciences

  collaborator OTHER

• University of Liverpool

  lead OTHER

Principal Investigators

• Tom Solomon, MRCP, PhD · Director,Institute of Infection and Global Health, University of Liverpool, Apex Building, 8 West Derby Street, Liverpool, L69 7BE, UK , Head- Liverpool Brain Infection Group

• Ajit Rayamajhi, MBBS, MD · Institute of Infection and Global Health, University of Liverpool, Liverpool, UK & Kanti Children's Hospital, Maharajgunj, Kathmandu, Nepal

• Sam Nightingale, MRCP · Institute of Infection and Global Health, University of Liverpool, Apex Building, 8 West Derby Street, Liverpool, L69 7BE, UK

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

1 Year

Max Age

14 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-05-31

Primary Completion

2009-08-31

Completion

2009-08-31

Countries

• Nepal

Study Locations