New Challenge Pool of Norwalk Virus Inoculum

• Status: Completed
• Trial end date: 2012-09-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Criteria

Inclusion Criteria:

• 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.

• 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.

Exclusion Criteria:

• 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.

• 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)