Diarrhea and Oral Polio Vaccine Immunity
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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 |
- 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.
- 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 |
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 LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT01559636
| Nepal | |
| Institute of Medicine | |
| Kathmandu, Nepal | |
| 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 February 26, 2015