Gastroenteritis Norovirus Clinical Trial
Official title:
Evaluation of a New Challenge Pool of Norwalk Virus Inoculum (Lot 42399) in Human Subjects
The main objective of this study is to see the number of volunteers that get sick from a Norwalk virus (NV) inoculation with typical symptoms of nausea, vomiting, and diarrhea. If this NV preparation is shown to cause Norwalk illness, then it can be used to test new vaccines in the future. Additionally, researchers hope to determine the lowest dose of NV inoculum that can be given to volunteers and cause illness. Study participants will include 57 healthy adults, ages 18-50. Participants will either be given the NV inoculum or placebo (water without virus). Participants will be hospitalized for a maximum of 7 days and a minimum of 4 days following the NV challenge. Study procedures include physical exam, blood testing, and collection of saliva, urine, and stool samples. Participants will be involved in study related procedures for up to 180 days.
Noroviruses are the cause of most acute, epidemic, non-bacterial gastroenteritis (24-hour intestinal flu) and Norwalk virus (NV) is the prototype strain of this group of viruses. Although NV was identified some 30 years ago, progress in understanding its molecular characteristics has been slow due to the inability to grow the virus in cell culture and the lack of an animal model. As such, most work must be performed in human volunteers. The principal source of virus for research has been stool samples obtained from human volunteers who were experimentally infected with NV (NIH-8fIIa) obtained from the National Institutes for Health (NIH). The quantities of NV were sufficient to characterize the entire genome and significant advances have been made. The original NV challenge pool, obtained from the NIAID/NIH, is no longer available. Using stored stool specimens obtained from an otherwise healthy subject who was infected approximately 14 years ago with NV (NIH-8fIIa), a new pool (filtrate) was produced. This study has been designed to support an IND application, for NV challenge pool Lot 42399, to be submitted by the DMID/NIAID/NIH. The safety and infectivity of the new NV challenge pool will be established by this protocol. The clinical attack rate of Lot 42399 will be determined. Initially, 20 subjects will be challenged with a dose of NV (Lot 42399) that approximates the dose used in previous challenge studies. The predicted rate of infection in this study, defined by fecal viral shedding or seroresponse, is at least 90% of those who receive inoculation. Approximately two-thirds of infected subjects are expected to become symptomatic. Subsequently, smaller groups of subjects will be challenged with lower dosages to determine the Human Infectious Dose 50 percent (HID50). The overall objective of this study is to develop a challenge pool/inoculum of NV. The specific objectives of this clinical study are: to determine the safety and acute toxicity of a new NV challenge pool; to determine the NV clinical attack rate; to determine the infection rate and HID50 of NV Lot 42399; to measure specific immunoglobulin responses to NV Lot 42399 inoculation/infection in blood, saliva and intestinal excretions; and examine peripheral blood mononuclear cells for the presence of NV. Study participants will include 57 healthy adults, ages 18-50. This double-blind study consists of informed consent, a screening and enrollment period, the NV challenge (inpatient NV inoculation phase), and a post challenge follow-up period. Many subjects participating in this study are expected to become ill with typical symptoms and signs of viral gastroenteritis. Subjects will be hospitalized, for up to a maximum of 7 days and minimum of 4 days. Participants will be involved in study related procedures for up to 180 days. ;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator)
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