Safety and Immunogenicity of Rotavirus Vaccine (RotaTeq(R)) in Infants With Short Bowel Syndrome
Condition: Short Bowel Syndrome
MeSH terms: Short Bowel Syndrome; Syndrome
Intervention: Oral, live, pentavalent rotavirus vaccine; RotaTeq(R)
Intervention description: Oral vaccine for prevention of rotavirus infection, 3 dose series
Intervention MeSH terms: Vaccines
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 6 Weeks
Maximum age: 18 Months
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Infant

Summary:

      Rotavirus infection is a common pediatric illness and is the leading cause of severe acute
      gastroenteritis (vomiting and diarrhea) in infants and young children. Since February of
      2006, an oral vaccine to prevent rotavirus has been approved by the Food and Drug
      Administration (FDA). The company that makes the oral vaccine is Merck and Company. Since the
      FDA approval, the American Academy of Pediatrics (AAP) and that Advisory Committee on
      Immunization Practices (ACIP) has recommended the use of this oral vaccine in infants. A
      previous rotavirus oral vaccine, Rotashield, was removed from the market for concerns that it
      was causing an increase in a gastrointestinal (GI) disease called intussusception. However,
      the new rotavirus vaccine was studied by the manufacturer and was not found to cause an
      increase in the cases of intussusception. Intussusception is a disease in which a portion of
      the GI tract folds back on itself leading to GI tract obstruction or back-up.

      The manufacturer of the vaccine noted on package insert information that the vaccine was not
      studied, originally, in infants with a history of GI disorders or in infants who have had
      surgery on their abdomen. Currently, there is no information available in the scientific
      literature about the use of the oral rotavirus vaccine in infants with GI diseases or those
      who have had GI surgeries.

      The objective of the study is the assessment of safety and tolerability of the oral RotaTeq®
      vaccine for all infants participating in the study. All infants will be followed for clinical
      adverse events with active safety surveillance for the first 42 days after each dose and also
      monthly afterward for a total of 12 months from the first vaccination date. The secondary
      objective of the study is to quantify the immunologic response will occur in all of the
      infants in the study. Assessment of percentage of the number of infants who have a good
      immune response (three-fold rise in IgA titer or greater) to the complete rotavirus vaccine
      series (three oral vaccines in total) by a blood test to check the rotavirus immunoglobulin A
      (IgA) level in infants with short bowel syndrome compared to normal infants will occur.

      Infants, meeting eligibility criteria and whose parents have signed informed consent will
      have their study information collected. These infants will be tested for the presence of
      pre-vaccine anti-rotavirus antibody, IgA levels, as mentioned above. After the blood is
      obtained, participants will receive their first oral rotavirus vaccine dose between the ages
      of 6 weeks to 12 weeks of life per package insert information. This oral rotavirus vaccine
      may be administered with other routine pediatric vaccines at the participant primary care
      provider's office. The date of the rotavirus vaccine and lot number would be recorded on
      vaccine administration date cards. Most participants will have their vaccines given through
      the Infectious Disease clinic staff at the Children's Hospital of Michigan.

      Subsequent doses of the oral rotavirus vaccine will be given at a minimal interval between
      vaccines of four weeks. The third, and final vaccine dose must be given by 32 weeks of life.
      Any adverse reactions to the vaccine will be reported on the National Vaccine Adverse Event
      Reporting System and MedWatch forms.

      Finally, two weeks after the participants have had all three oral rotavirus vaccine doses,
      the second and final blood draw will take place for measuring the post-vaccine level of
      anti-rotavirus antibody, IgA.

      Participants in the study will be monitored by telephone contacts on days 7, 14, and 42 after
      each dose and within 48 to 72 hours of each dose of the rotavirus vaccine regarding any
      serious adverse events. Each infant will also be assessed in the clinical setting each week
      after a vaccine dose has been given. As above, parents of participants will be asked to fill
      out the vaccine report card and record the child's temperature, and any episodes of vomiting,
      diarrhea, blood in the stools or fussiness for the first seven days. The parents will also be
      asked to record any other events from day 8 through 42 after each vaccine is administered
      such as fever, ear infection, runny nose, etc. Afterward, parents will also have monthly
      phone call safety follow-ups during the 12 month period following the first vaccination. A
      Data Safety and Monitoring Board will oversee the study and it's progress and will have the
      ability to vote to stop the study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Only those participants whose parents give full informed consent will be included in
             the study.

          -  Infants will be eligible for enrolment in the study arm if they have the diagnosis of
             short bowel syndrome (SBS) and are between the ages of 6 and 12 weeks of age before
             the start of the vaccine series.

          -  SBS infants must also be afebrile,

               -  have stable to increasing weight,

               -  have stable electrolytes and be clinically stable for home discharge (or already
                  discharged home), as assessed by the infant's primary care physicians, prior to
                  administration of the oral RotaTeq® vaccine.

          -  Study group infants must have at least 30 cm of residual small intestine with a whole
             colon and intact ileocecal valve or at least 45 cm of residual small intestine (with
             or without a whole colon) and without an ileocecal valve to be included in the study
             based on age-related normal lengths from the literature.

          -  The SBS infant should be at least 10 days post any gastrointestinal surgery at time of
             vaccine administration and be between 10- to 12- weeks of chronological age at time of
             first vaccine administration, and be tolerating at least some oral intake (liquids
             and/or food). The vaccine will not be given in the neonatal intensive care unit for
             the purposes of this study, although the risk of shedding is low with RotaTeq®
             vaccine.

          -  Infants will be eligible for inclusion in the control arm if they have no underlying
             chronic gastrointestinal medical conditions (Gastro-esophageal Reflux Disease (GERD),
             is allowed) and

          -  are between the ages of 6 and 12 weeks of age before the start of the vaccine series.

          -  Normal control arm infants will be estimated gestational age- and age-matched within
             14 days to study arm participants for more accurate comparison between the immune
             responses.

          -  These healthy infants will also receive their first vaccine administration at 10- to
             12-weeks of chronological age, when possible, so that the immune responses between the
             groups will be more comparable.

        Exclusion Criteria:

          -  Infants whose parents do not give full informed consent or whom do not meet inclusion
             criteria will be excluded from participation.

          -  Additionally, Infants who have a demonstrated history of hypersensitivity to any
             vaccine component will be excluded.

          -  Any infant who develops symptoms associated with hypersensitivity reactions after the
             first or second dose of the vaccine will also be excluded from the study and any
             further doses.

          -  Those infants with documented fever of greater than 100.5 degrees F. or severe illness
             by the end of their 12th week of life and who have not yet received the vaccine will
             be excluded.

          -  Any infant who fails to have blood obtained by the third attempt will be automatically
             excluded from the study.

          -  Infants with a history of rotavirus or history of receipt of any rotavirus vaccine
             will be excluded from the study.

          -  Those infants diagnosed with a congenital or acquired immunodeficiency or neoplasm
             will be excluded as will any patient who is potentially immunosuppressed (topical and
             inhaled corticosteroid use would allow for inclusion).

          -  Infants who have received immunoglobulins will also be excluded (history of receipt of
             other blood products is allowed).

          -  Short bowel infants with diagnosed portal hypertension will be excluded.

          -  Also, any short bowel syndrome infant who is listed or will likely need liver/bowel
             transplantation (imminent or evident liver failure due to total parenteral nutrition
             (TPN)-induced liver injury, a total bilirubin level of >7 mg/dl, or stage 2 liver
             fibrosis, or only two central venous access sites remain) will be excluded from the
             study.

          -  In the short bowel syndrome infants, the principal investigator reserves the right to
             exclude any infant on the basis of any clinical safety concern, such as a specific
             additional diagnosis, that exists or develops for the individual infant that may be
             seen as a potential risk factor for a future adverse event.

          -  Those infants with household contacts who have immunosuppressive conditions, such as
             infants residing in a household with an immunocompromised person, including
             individuals with congenital immunodeficiency, HIV infection, leukemia, lymphoma,
             Hodgkin's disease, multiple myeloma, generalized malignancy, chronic renal failure,
             nephritic syndrome, organ or bone marrow transplantation, or with those receiving
             immunosuppressive chemotherapy including long-term systemic corticosteroids will be
             excluded from the study.

          -  Any infant that cannot have adequate follow up for safety by telephone or home visit
             will be excluded from the study.