A Pilot Study of Influenza Viruses Isolated From Immunocompromised Children and Adolescents

Influenza, Human Clinical Trial

Official title:

A Pilot Study of Influenza Viruses Isolated From Immunocompromised Children and Adolescents

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02352389
• Other study ID #: FLUMUT
• Status: Completed
• Start date: March 30, 2015
• Est. completion date: December 8, 2022

Study information

• Verified date: December 2023
• Source: St. Jude Children's Research Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of the proposed study is to gather critical information that may be useful in designing effective prevention and treatment strategies for control of seasonal influenza and an influenza pandemic. In particular, the critical questions are related to the virus' ability to adapt to efficient replication and spread in humans.

Influenza is a contagious respiratory illness caused by influenza A and B viruses. Influenza infections result in about 230,000 hospitalizations and 36,000 deaths annually in the United States. Children with cancer are more likely to have serious influenza and complications than those who have no underlying medical problems. They are also more likely to have prolonged influenza illnesses and to shed influenza viruses from their noses for long periods of time (sometimes for months). Recent studies suggest that influenza viruses may also be carried and shed from the gastrointestinal tract. New types of influenza viruses emerge frequently through mutations that occur when the viruses replicate. These mutations allow the virus to escape from killing by the immune system and are, in large part, responsible for seasonal epidemics of influenza that occur in the fall or winter months. It is possible that viruses can mutate when they are carried in the respiratory or gastrointestinal tracts for long periods, potentially giving rise to viruses that spread more easily to other persons, cause more severe disease, lead to new influenza epidemics or make the viruses resistant to drugs used to treat influenza.

Researchers at St. Jude Children's Research Hospital want to learn about how influenza viruses mutate in immunocompromised children. They will investigate how long children with cancer carry influenza viruses in their nose, throat and gastrointestinal tract and the characteristics of any mutations that are found in these viruses.

Description:

Participants will have nasal, oral and stool specimens obtained at the time they are diagnosed with influenza infections, and 7, 14, 21 and 28 days later. The genome of influenza viruses that are isolated from these participants will be sequenced and compared to one another and to standard influenza strains.

PRIMARY OBJECTIVE:

• To determine the proportion of pediatric oncology patients with nasal and oropharyngeal shedding of influenza viruses at 7, 14, 21 and 28 days following the diagnosis of infection.

SECONDARY OBJECTIVES:

• To determine the proportion of gastrointestinal shedding of human influenza viruses.

• To determine the frequency and pattern of mutations in influenza viruses isolated from pediatric oncology patients.

• To explore the biological consequences of mutations in influenza viruses isolated from pediatric oncology patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: December 8, 2022
• Est. primary completion date: December 8, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

Inclusion Criteria:

• Less than 22 years of age.

• Currently receiving active therapy for malignant disease at St. Jude, excepting surgical therapy only, or has received a hematopoietic stem cell transplant in the last 6 months.

• Subject has had a positive test for influenza (by direct fluorescent antibody, nucleic acid amplification test or viral culture) within 72 hrs of the time of enrollment.

• Agrees to participate in the study.

• Able to understand and comply with planned study procedures.

• Is available for all study visits.

Exclusion Criteria:

• Contraindication to nasal (mid-turbinate) swabs (e.g. nasal lesion or obstruction)

• Has any condition that would, in the opinion of the investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.

• Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.

• Previous enrollment on study.

Related Conditions & MeSH terms

• Influenza, Human

Intervention

Other:
• Blood sample
Blood samples will be drawn and analyzed at Day 0, 7, 14, 21, and 28
• Nasal swab
Obtained on Day 0, 7, 14, 21 and 28.
• Oropharyngeal swab
Obtained on Day 0, 7, 14, 21 and 28.
• Stool sample
Obtained on Day 0, 7, 14, 21 and 28.
• Symptom checklist
Obtained on Day 0, 7, 14, 21 and 28.

Locations

Country	Name	City	State
United States	St. Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
St. Jude Children's Research Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with nasal shedding of influenza viruses	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as the proportion of pediatric oncology patients with nasal shedding of influenza viruses and its 95% confidence interval at days 7, 14, 21, and 28 days will be provided.	Day 0
Primary	Proportion of patients with nasal shedding of influenza viruses	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as the proportion of pediatric oncology patients with nasal shedding of influenza viruses and its 95% confidence interval at days 7, 14, 21, and 28 days will be provided.	Day 7
Primary	Proportion of patients with nasal shedding of influenza viruses	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as the proportion of pediatric oncology patients with nasal shedding of influenza viruses and its 95% confidence interval at days 7, 14, 21, and 28 days will be provided.	Day 14
Primary	Proportion of patients with nasal shedding of influenza viruses	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as the proportion of pediatric oncology patients with nasal shedding of influenza viruses and its 95% confidence interval at days 7, 14, 21, and 28 days will be provided.	Day 21
Primary	Proportion of patients with nasal shedding of influenza viruses	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as the proportion of pediatric oncology patients with nasal shedding of influenza viruses and its 95% confidence interval at days 7, 14, 21, and 28 days will be provided.	Day 28
Primary	Proportion of patients with oropharyngeal shedding of influenza viruses	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as the proportion of pediatric oncology patients with oropharyngeal shedding of influenza viruses and its 95% confidence interval at days 7, 14, 21, and 28 days will be provided.	Day 0
Primary	Proportion of patients with oropharyngeal shedding of influenza viruses	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as the proportion of pediatric oncology patients with oropharyngeal shedding of influenza viruses and its 95% confidence interval at days 7, 14, 21, and 28 days will be provided.	Day 7
Primary	Proportion of patients with oropharyngeal shedding of influenza viruses	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as the proportion of pediatric oncology patients with oropharyngeal shedding of influenza viruses and its 95% confidence interval at days 7, 14, 21, and 28 days will be provided.	Day 14
Primary	Proportion of patients with oropharyngeal shedding of influenza viruses	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as the proportion of pediatric oncology patients with oropharyngeal shedding of influenza viruses and its 95% confidence interval at days 7, 14, 21, and 28 days will be provided.	Day 21
Primary	Proportion of patients with oropharyngeal shedding of influenza viruses	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as the proportion of pediatric oncology patients with oropharyngeal shedding of influenza viruses and its 95% confidence interval at days 7, 14, 21, and 28 days will be provided.	Day 28
Secondary	Frequency of gastrointestinal shedding of human influenza virus	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as proportion of gastrointestinal shedding of human influenza viruses and its 95% confidence interval at days 7, 14, 21, and 28 days will be provided. Frequency of gastrointestinal shedding of human influenza virus and its 95% confidence interval at days 7, 14, 21, and 28 days will be provided.	Day 0
Secondary	Frequency of gastrointestinal shedding of human influenza virus	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as proportion of gastrointestinal shedding of human influenza viruses and its 95% confidence interval at days 7, 14, 21, and 28 days will be provided. Frequency of gastrointestinal shedding of human influenza virus and its 95% confidence interval at days 7, 14, 21, and 28 days will be provided.	Day 7
Secondary	Frequency of gastrointestinal shedding of human influenza virus	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as proportion of gastrointestinal shedding of human influenza viruses and its 95% confidence interval at days 7, 14, 21, and 28 days will be provided. Frequency of gastrointestinal shedding of human influenza virus and its 95% confidence interval at days 7, 14, 21, and 28 days will be provided.	Day 14
Secondary	Frequency of gastrointestinal shedding of human influenza virus	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as proportion of gastrointestinal shedding of human influenza viruses and its 95% confidence interval at days 7, 14, 21, and 28 days will be provided. Frequency of gastrointestinal shedding of human influenza virus and its 95% confidence interval at days 7, 14, 21, and 28 days will be provided.	Day 21
Secondary	Frequency of gastrointestinal shedding of human influenza virus	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as proportion of gastrointestinal shedding of human influenza viruses and its 95% confidence interval at days 7, 14, 21, and 28 days will be provided. Frequency of gastrointestinal shedding of human influenza virus and its 95% confidence interval at days 7, 14, 21, and 28 days will be provided.	Day 28
Secondary	Frequency of mutations in influenza viruses	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as proportion of human influenza viruses with mutations and its 95% confidence interval at days 7, 14, 21, and 28 days will be provided.	Day 0
Secondary	Frequency of mutations in influenza viruses	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as proportion of human influenza viruses with mutations and its 95% confidence interval at days 7, 14, 21, and 28 days will be provided.	Day 7
Secondary	Frequency of mutations in influenza viruses	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as proportion of human influenza viruses with mutations and its 95% confidence interval at days 7, 14, 21, and 28 days will be provided.	Day 14
Secondary	Frequency of mutations in influenza viruses	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as proportion of human influenza viruses with mutations and its 95% confidence interval at days 7, 14, 21, and 28 days will be provided.	Day 21
Secondary	Frequency of mutations in influenza viruses	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as proportion of human influenza viruses with mutations and its 95% confidence interval at days 7, 14, 21, and 28 days will be provided.	Day 28
Secondary	Number of mutations by type in influenza viruses	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as the type of mutations observed in human influenza viruses at days 7, 14, 21, and 28 days will be provided to show the pattern of mutations. Genetic variants are defined to meet a minimum minor allele frequency of 20%.	Day 0
Secondary	Number of mutations by type in influenza viruses	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as the type of mutations observed in human influenza viruses at days 7, 14, 21, and 28 days will be provided to show the pattern of mutations. Genetic variants are defined to meet a minimum minor allele frequency of 20%.	Day 7
Secondary	Number of mutations by type in influenza viruses	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as the type of mutations observed in human influenza viruses at days 7, 14, 21, and 28 days will be provided to show the pattern of mutations. Genetic variants are defined to meet a minimum minor allele frequency of 20%.	Day 14
Secondary	Number of mutations by type in influenza viruses	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as the type of mutations observed in human influenza viruses at days 7, 14, 21, and 28 days will be provided to show the pattern of mutations. Genetic variants are defined to meet a minimum minor allele frequency of 20%.	Day 21
Secondary	Number of mutations by type in influenza viruses	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as the type of mutations observed in human influenza viruses at days 7, 14, 21, and 28 days will be provided to show the pattern of mutations. Genetic variants are defined to meet a minimum minor allele frequency of 20%.	Day 28
Secondary	Biological consequences of mutations in influenza viruses	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as the proportion of mutations observed in human influenza viruses at days 7, 14, 21, and 28 days that are associated with antiviral resistance will be provided to show the biological consequences. Two-sample t-tests or Wilcoxon rank-sum tests will be performed as appropriate to compare isolates to parental influenza isolates from the same patients.	Day 0
Secondary	Proportion of mutations in influenza viruses by collection site	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as the proportion of mutations observed in human influenza viruses at days 7, 14, 21, and 28 days that are associated with antiviral resistance will be provided to show the biological consequences. Two-sample t-tests or Wilcoxon rank-sum tests will be performed as appropriate to compare isolates to parental influenza isolates from the same patients.	Day 7
Secondary	Proportion of mutations in influenza viruses by collection site	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as the proportion of mutations observed in human influenza viruses at days 7, 14, 21, and 28 days that are associated with antiviral resistance will be provided to show the biological consequences. Two-sample t-tests or Wilcoxon rank-sum tests will be performed as appropriate to compare isolates to parental influenza isolates from the same patients.	Day 14
Secondary	Proportion of mutations in influenza viruses by collection site	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as the proportion of mutations observed in human influenza viruses at days 7, 14, 21, and 28 days that are associated with antiviral resistance will be provided to show the biological consequences. Two-sample t-tests or Wilcoxon rank-sum tests will be performed as appropriate to compare isolates to parental influenza isolates from the same patients.	Day 21
Secondary	Proportion of mutations in influenza viruses by collection site	Day 0 is collected within 72 hours of diagnosis of influenza. Descriptive statistics, such as the proportion of mutations observed in human influenza viruses at days 7, 14, 21, and 28 days that are associated with antiviral resistance will be provided to show the biological consequences. Two-sample t-tests or Wilcoxon rank-sum tests will be performed as appropriate to compare isolates to parental influenza isolates from the same patients.	Day 28

External Links

•   Clinical Trials Open at St. Jude
•   St. Jude Children's Research Hospital