Gastroenteritis NorovirusPhase 1NCT00138476
New Challenge Pool of Norwalk Virus Inoculum
A Phase 1 study testing Norwalk Virus in people with Gastroenteritis Norovirus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Gastroenteritis Norovirus
- What is being tested?
- Norwalk Virus
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 57 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2004to Sep 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subjects must be 18 to 50 years of age and in good health as determined by medical history and physical examination.
- Subjects must sign informed consent prior to study initiation.
- All screening clinical laboratory test results within the protocol-defined normal range. Subjects with a history of positive Hepatitis A antibody or vaccination and normal liver transaminases (serum) may be accepted.
- If the subject is a woman, a negative serum pregnancy test within 3 days of inoculation and negative urine or blood pregnancy test on day of inoculation.
- Subjects must be able to demonstrate a sufficient understanding of the study protocol and the ability to follow all required study procedures, including measures to prevent Norwalk Virus (NV) contamination of the environment and spread of NV infection and illness to the community. The prospective subjects must pass (> 75 percent correct responses, or 21 of 27 questions answered correctly) a written examination before enrollment. The exam will contain 27 multiple choice or true/false questions on all aspects of the study protocol. Subjects will be re-instructed about any question they may have answered incorrectly.
- Subjects must be available to return for follow-up visits following discharge from the General Clinical Research Center (GCRC) and deliver specimens to the investigator promptly.
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- Agree to storage of unused, identifiable clinical specimens for an indefinite period at Baylor College of Medicine for use in future research.
- Subject must express the H type-1 oligosaccharide (as measured by positive salivary secretor status).
- Must use acceptable form of birth control, if female. The only acceptable birth control methods are oral contraceptives, intrauterine devices (IUDs), contraceptive implants under the skin, or contraceptive injections, and condoms with foam.
Who cannot join
- Living with or having daily contact with children age 10 years or less or a woman known to be pregnant. This includes contact at home, school, day-care, or equivalent facilities.
- Living with or having daily contact with childcare workers.
- Living with or having daily contact with elderly persons, aged 70 years or more, or the infirmed, diapered individuals, persons with disabilities or incontinent persons. This includes work or visits to nursing homes and day-care or equivalent facilities.
- Evidence of recent (within 3 months), or of current nonbacterial gastroenteritis suggestive of Norwalk Virus (NV) infection [vomiting or unformed or watery stools (>2 during a 24 hour period)].
- History of chronic functional dyspepsia, chronic gastroesophageal reflux disease, peptic ulcer disease, gastrointestinal hemorrhage, gall bladder disease, inflammatory bowel disease, irritable bowel syndrome, frequent diarrhea, or diverticulitis anytime during the subject's lifetime.
- Positive serological tests for hepatitis viruses B (core and/or surface antigen serology) and/or C, human immunodeficiency virus (HIV)-1, or syphilis. Prior to HIV-1 testing, subjects will be counseled by a qualified clinical investigator as to the purpose and meaning of such testing. Any subject with a positive test will be referred to the local HIV-1 clinic or his/her private practitioner.
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- Pregnant or lactating woman.
- History of drug or alcohol dependence, or significant acute or chronic medical or psychiatric illness that could limit the subject's ability to complete the study and/or compromise the objectives of the study. One positive CAGE questionnaire response is exclusionary.
- Regular use of medication, such as, but not limited to, corticosteroids, anti-diarrhea medications, opioids, immunosuppressive agents, nonsteroidal anti-inflammatory drugs, antipyretics, and anticoagulants (e.g., warfarin or heparin or gold salts). Oral contraceptives are permitted.
- Use of antibiotics within 14 days of inoculation.
- Use of an investigational drug within 30 days prior to the start of study drug.
- Evidence of renal disease, as indicated by (any of the following) , serum sodium, or serum potassium outside normal laboratory range, or BUN or serum creatinine >upper limit of normal range, or uric acid >8.5 mg/dL.
- A baseline serum amylase value of 115 IU/L or greater or a baseline serum lipase value of 210 IU/L or greater.
- Evidence of cardiovascular disease, as indicated by (any of the following) blood pressure >150/90 mm HG in two measurements on different days, hospitalization for myocardial infarction, arrhythmia, syncope, or murmur (non-functional) detected on physical examination.
- Evidence of liver or other reticuloendothelial disease as indicated by (any of the following) serum alanine aminotransferase (ALT) > 1.25 times normal, aspartate aminotransferase (AST) > 1.25 times normal, alkaline phosphatase > 1.25 times normal, hepatosplenomegaly, jaundice, or lymphadenopathy on physical examination.
- Evidence of hematologic, rheumatologic, or immunologic disease, as indicated by (any of the following) white blood cell count <3.0 thous./cu.mm, white blood cell count >11.0 thousand/cu.mm, neutropenia (<1500/cu.mm), hemoglobin outside laboratory normal range, history of more than 3 hospitalizations for invasive bacterial infections (pneumonia, meningitis), acute or chronic dermatitis (e.g., eczema, seborrhea, psoriasis) or collagen vascular disease [e.g., systemic lupus erythematosus (SLE) or dermatomyositis].
- History or evidence of diabetes mellitus or hyperglycemia (e.g., random glucose >120 mg/dL).
- The presence of other serious chronic illness (i.e., malignancy other than a resolved skin lesion, neurological condition or malnutrition).
- Bacterial gastroenteritis or positive fecal culture for salmonella, campylobacter, E. coli 0157:H7, and Shigella; positive fecal screen for ova and parasites with fecal white cell examination.
- Employment in the food service industry, such as restaurants, or cafeteria facilities. Specifically, this will include persons whose employment requires food processing in the 4 weeks following inoculation.
- Health-care workers with patient contact expected in the 4 weeks following inoculation.
- Expected contact (through employment or at home) with immunocompromised persons (HIV-positive, receiving immunosuppressive medications such as oral steroids, anti-neoplastic agents) in the 4 weeks following inoculation.
- Employment as an airline flight attendant scheduled to work in the 4 weeks following inoculation. Persons planning on taking a cruise in the 4 weeks following inoculation.
- Persons who have consumed or plan to consume raw shellfish (e.g., oysters) within 7 days prior to enrollment or throughout the study.
- Other conditions that in the opinion of the investigator might jeopardize the safety or rights of a volunteer subject participating in the trial or would render the subject unable to comply with the study protocol.
- Expresses blood group B histoblood group antigen (blood group B or AB)
Trial locations and contacts
1 site in 1 country.
United States1 site
Baylor College of Medicine - Molecular Virology and Microbiology
Houston, Texas, 77030-3411
About this study
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.
Read the 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.
- Conditions
- Gastroenteritis Norovirus
- Being tested
- Placebo, Norwalk Virus
- Keywords
- Norovirus, calicivirus, gastroenteritis, Norwalk virus, challenge
- Medical subject headings
- Gastroenteritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
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.
Norwalk VirusBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| Group 4: 0.48 RT-PCR units or Placebo | Experimental | Group 4: dosage group of 10 subjects will receive 0.48 RT-PCR units of Lot 42399 NV or placebo control (8 subjects will receive NV and 2 subjects will receive placebo control). Receives: Drug: Placebo; Biological: Norwalk Virus |
| Group 3: 4.8 RT-PCR units or Placebo | Experimental | Group 3: dosage group of 12 subjects will receive 4.8 RT-PCR units of Lot 42399 NV or placebo control (10 subjects will receive NV and 2 subjects will receive placebo control). Receives: Drug: Placebo; Biological: Norwalk Virus |
| Group 2: 48 RT-PCR units or Placebo | Experimental | Group 2: dosage group of 12 subjects will receive 48 RT-PCR units of Lot 42399 NV or placebo control (10 subjects will receive NV and 2 subjects will receive placebo control). Receives: Drug: Placebo; Biological: Norwalk Virus |
| Group 1: 4800 RT-PCR units or Placebo | Experimental | Group 1: dosage group of 11 subjects will receive 4800 reverse transcription polymerase chain reaction (RT-PCR) units of Lot 42399 Norwalk Virus (NV) or placebo control (9 subjects will receive NV and 2 subjects will receive placebo control). Receives: Drug: Placebo; Biological: Norwalk Virus |
| Validation Group: 4.8 and 0.48 RT-PCR units | Experimental | Validation Group: dosage group of 12 subjects, 4 will receive 4.8 RT-PCR units and 8 will receive 0.48 RT-PCR units of Lot 42399 NV. No placebo control. Receives: Biological: Norwalk Virus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the clinical attack rate for viral gastroenteritis induced by Norwalk Virus (NV) Lot 42399.
Measured: Up to 7 days or until clinical symptoms of diarrhea and vomiting have resolved.
Safety and acute toxicity of a new Norwalk virus challenge pool (Lot 42399) through clinical and laboratory monitoring of subjects.
Measured: Screening Days 30, 90, and 180
Determine the human infectious dose 50 percent of NV Lot 42399 based on viral shedding as measured by reverse transcription polymerase chain reaction (RT-PCR), by antigen shedding or by NV seroresponse by enzyme-linked immunosorbent assay (ELISA).
Measured: Screening, Days 2, 3, 4, 5, 6, 7, 14, 30, and 180.
Secondary outcomes (4)
Measure specific IgG and IgA immunoglobulin responses to NV Lot 42399 inoculation/infection by ELISA, in serum, saliva and stool.
Measured: Screening, Days 0, 1, 2, 3, 4, 5, 6, 7, 8-13, 14, 15-21, 28, 30, 35, 42, 49, 56 and 180.
Examine peripheral blood mononuclear cells for the presence of NV genome by RT-PCR.
Measured: Screening, Days 2, 7, 14, 30 and 180.
Examine a variety of serum cytokine responses including interferon alpha, interleukin-10, C-reactive protein, TNF-alpha and IL-6 to NV infection and correlate acute, convalescent, and recovery cytokine levels with illness severity.
Measured: Screening, Days 1, 2, 3, 4, 5, 6, 7, 30, 90, and 180.
Examine stool by immune electron microscopy for NV particles.
Measured: Screening, Days 0, 1, 2, 3, 4, 5, 6, 7, 8-13, 14, 15-21, 28+/-3, 30, 35+/-3, 42+/-3, 49+/-3, and 56+/-3.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2005 (estimated)
- Study startAug 2004
- Primary completionApr 2012
- Study completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Gastroenteritis NorovirusStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00138476
- Sponsor's protocol ID
- 99-036
- Other IDs
- BCM-IRB 10690; GCRC 2027, HHSN272200800002C
- Status last verified
- Apr 2012
- First submitted
- 26 Aug 2005
- Last updated
- 9 May 2014
- Results posted
- No
Publications
Atmar RL, Opekun AR, Gilger MA, Estes MK, Crawford SE, Neill FH, Ramani S, Hill H, Ferreira J, Graham DY. Determination of the 50% human infectious dose for Norwalk virus. J Infect Dis. 2014 Apr 1;209(7):1016-22. doi: 10.1093/infdis/jit620. Epub 2013 Nov 18.
PubMed 24253285Reeck A, Kavanagh O, Estes MK, Opekun AR, Gilger MA, Graham DY, Atmar RL. Serological correlate of protection against norovirus-induced gastroenteritis. J Infect Dis. 2010 Oct 15;202(8):1212-8. doi: 10.1086/656364.
PubMed 20815703
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of a New Challenge Pool of Norwalk Virus Inoculum (Lot 42399) in Human Subjects
- ClinicalTrials.gov ID
- NCT00138476
- Acronym / sponsor ID
- 99-036
- Conditions
- Gastroenteritis Norovirus
- Keywords
- Norovirus, calicivirus, gastroenteritis, Norwalk virus, challenge
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Aug 2004
- Primary completion
- Apr 2012 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 30 Aug 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Group 4: 0.48 RT-PCR units or Placebo | Experimental | Drug: Placebo, Biological: Norwalk VirusGroup 4: dosage group of 10 subjects will receive 0.48 RT-PCR units of Lot 42399 NV or placebo control (8 subjects will receive NV and 2 subjects will receive placebo control). |
| Group 3: 4.8 RT-PCR units or Placebo | Experimental | Drug: Placebo, Biological: Norwalk VirusGroup 3: dosage group of 12 subjects will receive 4.8 RT-PCR units of Lot 42399 NV or placebo control (10 subjects will receive NV and 2 subjects will receive placebo control). |
| Group 2: 48 RT-PCR units or Placebo | Experimental | Drug: Placebo, Biological: Norwalk VirusGroup 2: dosage group of 12 subjects will receive 48 RT-PCR units of Lot 42399 NV or placebo control (10 subjects will receive NV and 2 subjects will receive placebo control). |
| Group 1: 4800 RT-PCR units or Placebo | Experimental | Drug: Placebo, Biological: Norwalk VirusGroup 1: dosage group of 11 subjects will receive 4800 reverse transcription polymerase chain reaction (RT-PCR) units of Lot 42399 Norwalk Virus (NV) or placebo control (9 subjects will receive NV and 2 subjects will receive placebo control). |
| Validation Group: 4.8 and 0.48 RT-PCR units | Experimental | Biological: Norwalk VirusValidation Group: dosage group of 12 subjects, 4 will receive 4.8 RT-PCR units and 8 will receive 0.48 RT-PCR units of Lot 42399 NV. No placebo control. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Subjects must be 18 to 50 years of age and in good health as determined by medical history and physical examination.
- Subjects must sign informed consent prior to study initiation.
- All screening clinical laboratory test results within the protocol-defined normal range. Subjects with a history of positive Hepatitis A antibody or vaccination and normal liver transaminases (serum) may be accepted.
- If the subject is a woman, a negative serum pregnancy test within 3 days of inoculation and negative urine or blood pregnancy test on day of inoculation.
- Subjects must be able to demonstrate a sufficient understanding of the study protocol and the ability to follow all required study procedures, including measures to prevent Norwalk Virus (NV) contamination of the environment and spread of NV infection and illness to the community. The prospective subjects must pass (> 75 percent correct responses, or 21 of 27 questions answered correctly) a written examination before enrollment. The exam will contain 27 multiple choice or true/false questions on all aspects of the study protocol. Subjects will be re-instructed about any question they may have answered incorrectly.
Key exclusion criteria (26 listed)
- Living with or having daily contact with children age 10 years or less or a woman known to be pregnant. This includes contact at home, school, day-care, or equivalent facilities.
- Living with or having daily contact with childcare workers.
- Living with or having daily contact with elderly persons, aged 70 years or more, or the infirmed, diapered individuals, persons with disabilities or incontinent persons. This includes work or visits to nursing homes and day-care or equivalent facilities.
- Evidence of recent (within 3 months), or of current nonbacterial gastroenteritis suggestive of Norwalk Virus (NV) infection [vomiting or unformed or watery stools (>2 during a 24 hour period)].
- History of chronic functional dyspepsia, chronic gastroesophageal reflux disease, peptic ulcer disease, gastrointestinal hemorrhage, gall bladder disease, inflammatory bowel disease, irritable bowel syndrome, frequent diarrhea, or diverticulitis anytime during the subject's lifetime.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo120 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. | Drug | Group 1: 4800 RT-PCR units or Placebo, Group 2: 48 RT-PCR units or Placebo, Group 3: 4.8 RT-PCR units or Placebo, Group 4: 0.48 RT-PCR units or Placebo |
| Norwalk VirusPrepared 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. | Biological | Group 1: 4800 RT-PCR units or Placebo, Group 2: 48 RT-PCR units or Placebo, Group 3: 4.8 RT-PCR units or Placebo, Group 4: 0.48 RT-PCR units or Placebo, Validation Group: 4.8 and 0.48 RT-PCR units |
Primary outcome
Determine the clinical attack rate for viral gastroenteritis induced by Norwalk Virus (NV) Lot 42399.
Time frame: Up to 7 days or until clinical symptoms of diarrhea and vomiting have resolved.
Safety and acute toxicity of a new Norwalk virus challenge pool (Lot 42399) through clinical and laboratory monitoring of subjects.
Time frame: Screening Days 30, 90, and 180
Determine the human infectious dose 50 percent of NV Lot 42399 based on viral shedding as measured by reverse transcription polymerase chain reaction (RT-PCR), by antigen shedding or by NV seroresponse by enzyme-linked immunosorbent assay (ELISA).
Time frame: Screening, Days 2, 3, 4, 5, 6, 7, 14, 30, and 180.
4 secondary outcomes
Measure specific IgG and IgA immunoglobulin responses to NV Lot 42399 inoculation/infection by ELISA, in serum, saliva and stool.
Time frame: Screening, Days 0, 1, 2, 3, 4, 5, 6, 7, 8-13, 14, 15-21, 28, 30, 35, 42, 49, 56 and 180.
Examine peripheral blood mononuclear cells for the presence of NV genome by RT-PCR.
Time frame: Screening, Days 2, 7, 14, 30 and 180.
Examine a variety of serum cytokine responses including interferon alpha, interleukin-10, C-reactive protein, TNF-alpha and IL-6 to NV infection and correlate acute, convalescent, and recovery cytokine levels with illness severity.
Time frame: Screening, Days 1, 2, 3, 4, 5, 6, 7, 30, 90, and 180.
Examine stool by immune electron microscopy for NV particles.
Time frame: Screening, Days 0, 1, 2, 3, 4, 5, 6, 7, 8-13, 14, 15-21, 28+/-3, 30, 35+/-3, 42+/-3, 49+/-3, and 56+/-3.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2014.
- Results publication: PubMed 24253285Atmar RL, Opekun AR, Gilger MA, Estes MK, Crawford SE, Neill FH, Ramani S, Hill H, Ferreira J, Graham DY. Determination of the 50% human infectious dose for Norwalk virus. J Infect Dis. 2014 Apr 1;209(7):1016-22. doi: 10.1093/infdis/jit620. Epub 2013 Nov 18.
- Derived from this study: PubMed 20815703Reeck A, Kavanagh O, Estes MK, Opekun AR, Gilger MA, Graham DY, Atmar RL. Serological correlate of protection against norovirus-induced gastroenteritis. J Infect Dis. 2010 Oct 15;202(8):1212-8. doi: 10.1086/656364.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Norwalk Virus in people with Gastroenteritis Norovirus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine the clinical attack rate for viral gastroenteritis induced by Norwalk Virus (NV) Lot 42399. (time frame: Up to 7 days or until clinical symptoms of diarrhea and vomiting have resolved.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00138476, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2014.