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Potential Mechanisms for Intussusception After Rotavirus Vaccine-Pilot Study

Primary Purpose

Intussusception, Rotavirus Infections

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Rotarix®,
Rotarix®, with other routine vaccines
RotaTeq®,
RotaTeq®, with other routine vaccines
Sponsored by
Children's Hospital Medical Center, Cincinnati
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Intussusception focused on measuring mechanisms for intussusception, rotavirus vaccine

Eligibility Criteria

42 Days - 90 Days (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. healthy infant 6 to 13 weeks (12 weeks and 6 days) of age at day of rotavirus vaccine administration
  2. free of obvious health problems as established by medical history and confirmed with infant's primary physician prior to Visit 1
  3. parent/legal guardian willing to have infant feed from a bottle for contrast
  4. parent/legal guardian willing and capable of signing informed consent
  5. parent/legal guardian and infant expected to be available for entire study
  6. parent/legal guardian can be reached by telephone
  7. parent/legal guardian expresses willingness to complete study procedures and receive 2 month immunizations, according to recommended schedule

Exclusion Criteria:

  1. gestational age of <37 weeks
  2. infant unable to fast for 4 hours prior to MRI procedure
  3. receipt of any vaccine except initial HBV (must have at least 28 days between HBV and Visit 1 to be included)
  4. history of severe allergic reaction to HBV vaccine
  5. contraindications for any of the routine vaccines

    1. Severe Combined Immune Deficiency
    2. history of intussusception
  6. precautions for either RV1 or RV5 (may interfere with study outcomes)

    a. altered immunocompetence i. infants with primary and acquired immunodeficiency states, cellular immunodeficiency, hypogammaglobulinemic and dysgammaglobulinemic states ii. infants with blood dyscrasias, leukemia, lymphomas, or other malignant neoplasms affecting the bone marrow or lymphatic system iii. infants on immunosuppressive therapy (including high-dose systemic corticosteroids) iv. infants who are HIV-exposed or infected b. acute gastroenteritis c. moderate or severe acute illness with or without fever d. pre-existing chronic gastrointestinal diseases (e.g., congenital malabsorption syndromes, Hirschsprung's disease, or short-gut syndrome) e. infants with spina bifida or bladder exstrophy (latex rubber is contained in the RV1 oral applicator)

  7. sensitivity to latex (latex rubber is contained in the RV1 oral applicator)
  8. febrile illness within previous 14 days (axillary temperature of 100.4◦ F or higher)
  9. history of vomiting (forceful expulsion of partially digested milk/food) and/or diarrhea (3 watery stools) within 14 days of Visit 1
  10. receipt of any steroids, immunoglobulins, other blood products/transfusion
  11. receipt of non-steroidal anti-inflammatory drugs in previous 72 hours (may affect cytokine response)
  12. receipt of an antipyretic medication (acetaminophen or ibuprofen) within 72 hours prior to the first dose of rotavirus vaccine or is already planning to administer a prophylactic antipyretic medication on the day of and the day following vaccination (this exclusion does not apply if the caretaker indicates he/she might administer antipyretics after vaccination to reduce a fever)
  13. is enrolled or plans to enroll in another clinical trial with an investigational product while participating in this study (observational studies are allowed)
  14. any condition which, in the opinion of the investigators, may post a health risk to the subject or interfere with the MRI or vaccine evaluation
  15. currently receiving medication for gastroesophageal reflux (GERD) or any other gastrointestinal condition including colic
  16. infant who is a relative of any research study personnel
  17. allergy to barium
  18. failed newborn hearing screening

    -

Sites / Locations

  • Cincinnati Children's Hosptital Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

Rotarix® alone

Rotarix®,with other routine vaccines

RotaTeq®, alone

RotaTeq®,with other routine vaccines

Arm Description

monovalent rotavirus vaccine (Rotarix®, RV1)

monovalent rotavirus vaccine (Rotarix®, RV1), plus additional immunizations

pentavalent rotavirus vaccine (RotaTeq®, RV5)

pentavalent rotavirus vaccine (RotaTeq®,RV5) plus additional immunizations

Outcomes

Primary Outcome Measures

The Effects of RV1 and RV5 With or Without Other Routine Immunizations on Gastrointestinal Anatomy
Number of subjects with an increase in the number of abdominal lymph nodes, as measured by abdominal ultrasound, or an increase of 1 mm or more of terminal ileum wall thickness, as measured by abdominal MRI, from Day 0 (Visit 1) to Day 4-6 (Visit 2)
The Feasibility of Conducting a Larger Scale Study as Determined by Study Recruitment Rates (Number of Participants Eligible/Participants Who Enrolled)
Study will be determined to be feasible on a larger scale if 10% or more of eligible subjects enroll in the study
The Feasibility of Conducting a Larger Scale Study as Determined by the Percentage of Participants Who Completed All Study Visits
Study will be determined to be feasible on a larger scale if 70% or more of randomized subjects complete all study visits and remain in the study until completion

Secondary Outcome Measures

Full Information

First Posted
June 24, 2015
Last Updated
July 11, 2018
Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
Centers for Disease Control and Prevention
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1. Study Identification

Unique Protocol Identification Number
NCT02542462
Brief Title
Potential Mechanisms for Intussusception After Rotavirus Vaccine-Pilot Study
Official Title
Potential Mechanisms for Intussusception After Rotavirus Vaccine-Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
November 2015 (Actual)
Primary Completion Date
May 2017 (Actual)
Study Completion Date
May 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
Centers for Disease Control and Prevention

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a prospective randomized clinical trial that aims to evaluate the potential effects of the first dose of rotavirus vaccines on gastrointestinal motility and anatomy and blood and stool cytokine responses. It will also assess the association between these outcomes and the pattern of the shedding of vaccine strain rotavirus in the stool. Infants will be randomized to one of four arms: monovalent rotavirus vaccine (Rotarix®, RV1) alone, RV1 with other recommended vaccines, pentavalent rotavirus vaccine (RotaTeq®, RV5) alone, or RV5 with other recommended vaccines. Data derived from the pilot study will be used to assess the feasibility of conducting a larger scale study.
Detailed Description
Healthy infants 6-13 weeks of age will be randomized (1:1:1:1) to receive either, RV1 alone, RV1 with Advisory Committee on Immunization Practices (ACIP) routinely recommended immunizations (Diphtheria, Tetanus and Pertussis (DTaP), Haemophilus influenza type b (Hib), pneumococcal conjugate (PCV13), Hepatitis B (HBV) and inactivated polio (IPV)), RV5 alone or RV5 with ACIP routinely recommended immunizations. Imaging study personnel and parents will be blinded to the rotavirus vaccine type; parents will be informed about the rotavirus vaccine type at the completion of the study. Up to 100 infants will be enrolled. Recruitment and enrollment will occur prior to the first clinic visit. There will be four study visits including the recruitment/enrollment visit and three clinic visits. Infants will be randomized to either RV1, RV1 plus other immunizations, RV5 alone, or RV5 plus other immunizations. Clinic Visit 1 (day 0) will include blood, saliva, stool and breast milk collection . The MRI and ultrasound will be performed prior to vaccination. Children will receive the immunizations to which they are randomized. Imaging personnel and parents will be blinded to rotavirus vaccine type; they will be informed about other vaccines administered. A second MRI and ultrasound will be performed at Clinic Visit 2 (day 5) and blood and stool samples collected. Parents will be unblinded at the completion of Clinic Visit 3 (day 14). Arrangements will be made to get remaining doses of same rotavirus vaccine. Daily stool samples will be collected at home during the 15 day study period (on vaccination day 0 and for next 14 days). A memory aid will be completed to collect reactogenicity data on days 0 and for the next 14 days. Remaining stools and reactogenicity data from parents will be collected at Visit 3. The investigators will assess blood and stool cytokine responses and intestinal anatomy and motility after rotavirus vaccination by comparing pre-vaccination with post-vaccination responses in the study infants. Cytokines and intestinal anatomy and motility will be assessed at baseline (Visit 1, the day of vaccine receipt) and 5 days after vaccination (Visit 2). For both blood and stool, the following cytokines will be tested: IL-2, IL-6, IL-7, IL-8, IL-15, INF-γ and TNF-α. Additional biomarkers may be studied.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Intussusception, Rotavirus Infections
Keywords
mechanisms for intussusception, rotavirus vaccine

7. Study Design

Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Care ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
144 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Rotarix® alone
Arm Type
Active Comparator
Arm Description
monovalent rotavirus vaccine (Rotarix®, RV1)
Arm Title
Rotarix®,with other routine vaccines
Arm Type
Active Comparator
Arm Description
monovalent rotavirus vaccine (Rotarix®, RV1), plus additional immunizations
Arm Title
RotaTeq®, alone
Arm Type
Active Comparator
Arm Description
pentavalent rotavirus vaccine (RotaTeq®, RV5)
Arm Title
RotaTeq®,with other routine vaccines
Arm Type
Active Comparator
Arm Description
pentavalent rotavirus vaccine (RotaTeq®,RV5) plus additional immunizations
Intervention Type
Drug
Intervention Name(s)
Rotarix®,
Other Intervention Name(s)
Rotavirus vaccine
Intervention Description
Single oral dose of licensed rotavirus vaccine given alone
Intervention Type
Drug
Intervention Name(s)
Rotarix®, with other routine vaccines
Other Intervention Name(s)
Rotavirus vaccine
Intervention Description
Single oral dose of licensed rotavirus vaccine given with other routine vaccines
Intervention Type
Drug
Intervention Name(s)
RotaTeq®,
Other Intervention Name(s)
Rotavirus vaccine
Intervention Description
Single oral dose of licensed rotavirus vaccine given alone
Intervention Type
Drug
Intervention Name(s)
RotaTeq®, with other routine vaccines
Other Intervention Name(s)
Rotavirus vaccine
Intervention Description
Single oral dose of licensed rotavirus vaccine given with other routine vaccines
Primary Outcome Measure Information:
Title
The Effects of RV1 and RV5 With or Without Other Routine Immunizations on Gastrointestinal Anatomy
Description
Number of subjects with an increase in the number of abdominal lymph nodes, as measured by abdominal ultrasound, or an increase of 1 mm or more of terminal ileum wall thickness, as measured by abdominal MRI, from Day 0 (Visit 1) to Day 4-6 (Visit 2)
Time Frame
4- 6 days
Title
The Feasibility of Conducting a Larger Scale Study as Determined by Study Recruitment Rates (Number of Participants Eligible/Participants Who Enrolled)
Description
Study will be determined to be feasible on a larger scale if 10% or more of eligible subjects enroll in the study
Time Frame
15 months
Title
The Feasibility of Conducting a Larger Scale Study as Determined by the Percentage of Participants Who Completed All Study Visits
Description
Study will be determined to be feasible on a larger scale if 70% or more of randomized subjects complete all study visits and remain in the study until completion
Time Frame
15 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
42 Days
Maximum Age & Unit of Time
90 Days
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: healthy infant 6 to 13 weeks (12 weeks and 6 days) of age at day of rotavirus vaccine administration free of obvious health problems as established by medical history and confirmed with infant's primary physician prior to Visit 1 parent/legal guardian willing to have infant feed from a bottle for contrast parent/legal guardian willing and capable of signing informed consent parent/legal guardian and infant expected to be available for entire study parent/legal guardian can be reached by telephone parent/legal guardian expresses willingness to complete study procedures and receive 2 month immunizations, according to recommended schedule Exclusion Criteria: gestational age of <37 weeks infant unable to fast for 4 hours prior to MRI procedure receipt of any vaccine except initial HBV (must have at least 28 days between HBV and Visit 1 to be included) history of severe allergic reaction to HBV vaccine contraindications for any of the routine vaccines Severe Combined Immune Deficiency history of intussusception precautions for either RV1 or RV5 (may interfere with study outcomes) a. altered immunocompetence i. infants with primary and acquired immunodeficiency states, cellular immunodeficiency, hypogammaglobulinemic and dysgammaglobulinemic states ii. infants with blood dyscrasias, leukemia, lymphomas, or other malignant neoplasms affecting the bone marrow or lymphatic system iii. infants on immunosuppressive therapy (including high-dose systemic corticosteroids) iv. infants who are HIV-exposed or infected b. acute gastroenteritis c. moderate or severe acute illness with or without fever d. pre-existing chronic gastrointestinal diseases (e.g., congenital malabsorption syndromes, Hirschsprung's disease, or short-gut syndrome) e. infants with spina bifida or bladder exstrophy (latex rubber is contained in the RV1 oral applicator) sensitivity to latex (latex rubber is contained in the RV1 oral applicator) febrile illness within previous 14 days (axillary temperature of 100.4◦ F or higher) history of vomiting (forceful expulsion of partially digested milk/food) and/or diarrhea (3 watery stools) within 14 days of Visit 1 receipt of any steroids, immunoglobulins, other blood products/transfusion receipt of non-steroidal anti-inflammatory drugs in previous 72 hours (may affect cytokine response) receipt of an antipyretic medication (acetaminophen or ibuprofen) within 72 hours prior to the first dose of rotavirus vaccine or is already planning to administer a prophylactic antipyretic medication on the day of and the day following vaccination (this exclusion does not apply if the caretaker indicates he/she might administer antipyretics after vaccination to reduce a fever) is enrolled or plans to enroll in another clinical trial with an investigational product while participating in this study (observational studies are allowed) any condition which, in the opinion of the investigators, may post a health risk to the subject or interfere with the MRI or vaccine evaluation currently receiving medication for gastroesophageal reflux (GERD) or any other gastrointestinal condition including colic infant who is a relative of any research study personnel allergy to barium failed newborn hearing screening -
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mary A. Staat, MD, MPH
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Karen Broder, MD
Organizational Affiliation
Centers for Disease Control and Prevention
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cincinnati Children's Hosptital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Potential Mechanisms for Intussusception After Rotavirus Vaccine-Pilot Study

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