New Challenge Pool of Norwalk Virus Inoculum
Condition: Gastroenteritis Norovirus
MeSH terms: Gastroenteritis
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Placebo; Norwalk Virus
Intervention type(s): Drug; Biological
Intervention description(s): 120 mL of the sodium bicarbonate solution, followed by 82 mL of sterile water, United States Pharmacopeia (USP) without virus; followed by 500 mg of sodium bicarbonate aqueous solution taken 5 minutes after placebo inoculation.; Prepared and packaged from liquid feces (DC544) by clarification, centrifugation, and serial dilutions; desired doses [reverse transcription polymerase chain reaction (RT-PCR) Units] 4800, 48, 4.8, 0.48.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Keywords: Norovirus, calicivirus, gastroenteritis, Norwalk virus, challenge