Clinical Trial: Safety and Efficacy Study of Intravenous Immunoglobulin to Treat Japanese Encephalitis
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: A Randomized Double Blind Placebo Controlled Trial to Assess the Safety and Efficacy of Intravenous Immunoglobulin (IVIG) in Children With Japanese Encephalitis in Nepal
Brief 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.
Detailed Summary:
Japanese encephalitis (JE) is the most important epidemic encephalitis worldwide, causing approximately 35-50,000 cases and 10-15,000 deaths annually. Half of the survivors have severe neuropsychiatric sequelae, posing a large socio-economic burden on communities that can ill afford it. JE virus (JEV, genus flavivirus, family Flaviviridae) has a 50 nm lipoprotein envelope surrounding a nucleocapsid comprised of core protein and 11 KB of single-stranded positive-sense RNA. The genome has 5' and 3' untranslated regions (UTR), and a single open reading frame encoding genes for three structural proteins (core - C, pre-membrane - prM and envelope - E) and 7 non-structural (NS) proteins. The E protein is critical for viral attachment and entry into cells, and along with NS1 and NS3 is a major target of the immune response.
JEV is an arthropod-borne virus (arbovirus), transmitted in an enzootic cycle between birds, pigs and other vertebrates by mosquitoes, especially Culex species. Almost all of the population in affected parts of Asia is infected by early adulthood, but only a small proportion (about 1 in 300) develops clinical features. These may range from a non-specific febrile illness to a severe meningoencephalitis, in which seizures and clinical signs of raised intracranial pressure are common, and carry a poor prognosis. In addition JEV causes a poliomyelitis-like flaccid paralysis. The distribution of the four genotypes of JEV across Asia was thought to explain the clinical epidemiology, but is now thought to be a reflection of the virus' origin in Southeast Asia, and spread from here. However subtle differences in the genome may be important in determining neurological presentations of flaviviruses.
Although there are vaccines against JEV, they are not available for many of the people that need them, because of issues o
Sponsor: University of Liverpool
Current Primary Outcome: Evidence of side effects of study drug such as infusion site reaction, diarrhea, rise in blood pressure and change in urinary output [ Time Frame: Every 12 hours after administration of study drug upto discharge, which is on average eigth day (192 hours) of hospital admission ]
Original Primary Outcome: Same as current
Current Secondary Outcome: Death or neurological sequelae [ Time Frame: At the time of discharge, an expected average of eighth day of admission and again at 6 months after discharge ]
At the time of discharge(expected average of eighth day of admission) or death: Time to death, to recover from coma, to sit independently, to stand independently, to walk at least 5m independently, and to leave hospital.
At 6 months after discharge: history of further seizures, behavioral changes, evidence of recovery of neurological sequelae such as assessment of ability to sit independently, to stand independently, to walk at least 5 meters independently.
Original Secondary Outcome: Same as current
Information By: University of Liverpool
Dates:
Date Received: May 5, 2013
Date Started: May 2009
Date Completion:
Last Updated: May 18, 2013
Last Verified: May 2013
