Diarrhea and Oral Polio Vaccine Immunity

This study has been withdrawn prior to enrollment.
(Study design altered and is no longer a clinical trial.)
Sponsor:
Collaborator:
Tribhuvan University, Nepal
Information provided by (Responsible Party):
Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:
NCT01559636
First received: January 4, 2012
Last updated: January 3, 2013
Last verified: January 2013
  Purpose

Global eradication of poliomyelitis has proven to be elusive. Although 99% of cases have been eliminated since 1988, outbreaks continue to occur in Africa and Asia, and new tools are needed to accelerate eradication. One concern in this effort is that many children in Southeast Asia have decreased immunogenicity to oral poliovirus vaccine (OPV), which may be related to the high rates of diarrheal disease in this population.

This project will evaluate the effect of diarrhea, and treatment of diarrhea, on seroconversion to OPV among children 6-36 months of age who reside in Nepal. Diarrhea is a frequent cause of illness among Nepali children; etiologies are diverse and include parasites, viruses, and bacteria. The investigators will conduct a randomized, controlled clinical trial that will assess whether treatment of diarrhea with a broad-spectrum antimicrobial, nitazoxanide, decreases length of illness, and results in improved immune response to a supplemental dose of OPV. Immune responses will be compared among children with diarrhea who receive nitazoxanide, children with diarrhea who receive the standard of care, and healthy children without diarrheal disease.

The results from this study will result in a better understanding of the factors that may decrease the ability of some children to seroconvert to OPV and be protected from poliomyelitis infection. This study also will provide information that could potentially lead to the introduction of a new agent, nitazoxanide, for diarrheal treatment as well as a poliomyelitis eradication tool in these at-risk populations.


Condition Intervention Phase
Poliomyelitis Seroconversion
Diarrhea
Drug: Nitazoxanide
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Diarrheal Disease, and Treatment for Diarrhea, on Oral Polio Vaccine (OPV) Seroconversion

Resource links provided by NLM:


Further study details as provided by Centers for Disease Control and Prevention:

Primary Outcome Measures:
  • The proportion of children who seroconvert or boost in antibody titers in study arm A (nitazoxanide) compared to study arm B (placebo) [ Time Frame: 4 weeks after date of OPV dose ] [ Designated as safety issue: No ]

    Seropositive: antibody titer of at least 1:8 for poliovirus type 1, 2, or 3

    Seronegative: antibody titer of less than 1:8 for poliovirus type 1, 2, or 3

    Seroconversion: proportion of children who change from seronegative to seropositive to types 1 or 3, four weeks after receipt of bOPV.

    Boost (increase in titer): seropositives at baseline who increase at least 4-fold in antibody titer four weeks after receipt of bOPV.


  • The proportion of children who seroconvert or boost in antibody titers in study arm B (diarrhea, placebo) compared to study arm C (no diarrhea). [ Time Frame: 4 weeks after date of OPV dose ] [ Designated as safety issue: No ]

    Seropositive: antibody titer of at least 1:8 for poliovirus type 1, 2, or 3

    Seronegative: antibody titer of less than 1:8 for poliovirus type 1, 2, or 3

    Seroconversion: proportion of children who change from seronegative to seropositive to types 1 or 3, four weeks after receive bOPV.

    Boost (increase in titer): seropositives at baseline who increase at least 4-fold in antibody titer four weeks after receipt of bOPV.



Secondary Outcome Measures:
  • Proportion of children with a diarrheal etiology that can be treated by nitazoxanide who were seronegative or had a low titer at baseline, who seroconverted or demonstrated a boost in titer, after being treated with nitazoxanide vs. placebo [ Time Frame: 4 weeks after date of OPV dose ] [ Designated as safety issue: No ]
  • Duration of diarrheal illness in study arm A (nitazoxanide) vs. study arm B (placebo) [ Time Frame: From date of first dose (drug or placebo) to date of resolution of diarrhea; participants will be followed for the duration of the study, up to five weeks ] [ Designated as safety issue: No ]
    Diarrhea is defined as three or more loose stools in a 24 hour period

  • Proportion of children in study arm A (nitazoxanide) experiencing side effects vs. study arm B (placebo) [ Time Frame: From date of first dose (drug or placebo) to date of end of therapy (three days expected) ] [ Designated as safety issue: Yes ]
  • Frequencies of parasitic, viral, and bacterial infections isolated in stool among children with diarrhea vs. healthy children [ Time Frame: Date of enrollment ] [ Designated as safety issue: No ]
    One stool sample will be collected from each child the day of enrollment, from children with and without diarrhea.


Enrollment: 0
Study Start Date: May 2012
Estimated Study Completion Date: November 2012
Estimated Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nitazoxanide
Children with diarrhea will have blood and stool sample taken and receive nitazoxanide (as well as zinc and ORS). After completion of therapy, they will receive bOPV. Four weeks later, seroconversion will be measured.
Drug: Nitazoxanide
<12 months of age: 7.5mg/kg per dose, twice daily for 3 days 12-36 months of age: 100 mg per dose, twice daily for 3 days
Other Name: Alinia for Oral Suspension
Placebo Comparator: Placebo suspension
Children with diarrhea will have blood and stool sample taken and receive zinc, ORS and placebo suspension. After 3 days they will receive bOPV. Four weeks later, they will have seroconversion measured.
Drug: Placebo
The placebo will be manufactured with a resulting suspension that is indistinguishable in taste, color and odor from Alinia for Oral Suspension.
No Intervention: Non-diarrhea
Children without diarrhea will have blood and stool sample taken and receive bOPV. Four weeks later another blood sample will be drawn to measure seroconversion.

  Eligibility

Ages Eligible for Study:   6 Months to 36 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • The investigators will be including Nepali infants and children aged at least 6 months and no more than 36 months, who have received ≤3 doses of OPV (cumulative from routine and SIA) and present to outpatient clinics in participating study sites. Whenever possible, the child's immunization status based on the caretaker's report will be cross-checked with available immunization cards.
  • Children receiving nitazoxanide or placebo also must have:
  • Current diarrhea, defined as three loose stools per day in the past 24 hours. This may include children with acute or chronic diarrhea, low grade fever, and those with intermittent vomiting who are able to tolerate oral fluids and do not present with severe dehydration on the initial visit.
  • Non-diarrhea children also must:
  • Present with other, non-diarrheal minor acute complaints. This can include but is not limited to children presenting for non-severe illnesses such as skin problems (e.g., rash), conjunctivitis, and mild cough, congestion, or cold. These children should be diarrhea-free for at least two weeks prior to enrolment.

Exclusion Criteria:

  • Infants younger than 6 months or children older than 36 months
  • Children who have received more than 3 cumulative doses of OPV (including both routine and SIAs)
  • Children who require hospitalization or are deemed too ill to participate by the study site clinician
  • Children with blood in the stool (as this may represent more severe cases including dysentery, or non-infectious severe illnesses such as intussusception)
  • Children who require IV medications for a severe illness (e.g., pneumonia); however, this does not include medications for mild or moderate illnesses, such as paracetamol, ORS, eye ointment, etc.
  • Children who have a chronic underlying illness requiring long term medications
  • Children who are unable to take any oral fluids by mouth, require IV hydration and therefore would be unable to tolerate oral medications in the study
  • Children whose caregivers do not consent, or are not present to give consent, to the study
  • Children who will not be able to return to the clinic to participate the full length of the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01559636

Locations
Nepal
Institute of Medicine
Kathmandu, Nepal
Sponsors and Collaborators
Tribhuvan University, Nepal
Investigators
Principal Investigator: Cristina V Cardemil, MD, MPH Centers for Disease Control and Prevention
  More Information

Additional Information:
No publications provided

Responsible Party: Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier: NCT01559636     History of Changes
Other Study ID Numbers: CDC-458-GID-037
Study First Received: January 4, 2012
Last Updated: January 3, 2013
Health Authority: United States: Federal Government

Keywords provided by Centers for Disease Control and Prevention:
seroconversion
oral polio vaccine
OPV
poliomyelitis
diarrhea

Additional relevant MeSH terms:
Diarrhea
Poliomyelitis
Central Nervous System Diseases
Central Nervous System Infections
Central Nervous System Viral Diseases
Enterovirus Infections
Myelitis
Nervous System Diseases
Neuromuscular Diseases
Picornaviridae Infections
RNA Virus Infections
Signs and Symptoms
Signs and Symptoms, Digestive
Spinal Cord Diseases
Virus Diseases
Nitazoxanide
Anti-Infective Agents
Antiparasitic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014