Nasal Flu Vaccine for COPD

Overseen By Caleb Hemphill

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of North Carolina, Chapel Hill

Must not be taking: Antibiotics, Prednisone, Corticosteroids, others

Disqualifiers: Asthma, Immunosuppression, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 3 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a nasal flu vaccine in people with COPD, a lung condition that makes breathing difficult, to observe their nasal immune system's response. It examines individuals with frequent COPD flare-ups, those without, and healthy individuals for comparison. The study aims to understand how the nasal immune system and flu virus behave differently in each group. Ideal participants are those diagnosed with COPD who have experienced two or more flare-ups requiring antibiotics or steroids in the past year, or have infrequent flare-ups, and have been symptom-free for the last four weeks. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking medical research.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop using certain medications. You cannot participate if you use regular suppressive antibiotics, daily oral prednisone, intranasal corticosteroids within 30 days prior to screening, or chronic immunosuppression within 30 days prior to screening. Additionally, you cannot use blood thinners beyond full dose aspirin.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that the Live Attenuated Influenza Vaccine (LAIV) is generally safe for most people. Studies involving groups such as asthma patients indicate that LAIV is well-tolerated. Most participants did not experience major safety issues, though some might have mild side effects like a runny nose or sore throat.

For individuals with Chronic Obstructive Pulmonary Disease (COPD), regular flu vaccines are often recommended to help prevent serious flu-related complications. Although specific safety data for LAIV in COPD patients is limited, the vaccine has been used in other groups with similar conditions without major issues.

As this study is in its early phase, researchers are closely monitoring safety. The safety results from these early studies are crucial before proceeding further. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for COPD?

Researchers are excited about the nasal flu vaccine for COPD because it offers a unique delivery method that could enhance convenience and compliance compared to traditional flu shots. Unlike standard care options that typically involve injectable vaccines, this treatment uses a live attenuated influenza vaccine (LAIV) administered through the nose. This approach could potentially provide a more natural immune response and is less invasive, making it particularly appealing for individuals with COPD who often face respiratory challenges. Additionally, the nasal route might offer faster protection by targeting the respiratory tract directly, which is crucial for COPD patients who are prone to lung infections.

What evidence suggests that this nasal flu vaccine might be an effective treatment for COPD?

Research has shown that the flu vaccine can benefit people with chronic obstructive pulmonary disease (COPD). This trial will evaluate the nasal flu vaccine, LAIV, in different groups: those with frequent exacerbations, those with infrequent exacerbations, and healthy controls. Studies have found that the flu shot can reduce the number of flare-ups or symptom worsening. These benefits appear in people with COPD who receive annual vaccinations. No strong evidence suggests that the flu shot causes more flare-ups immediately after administration. Overall, the flu vaccine is recommended for people with COPD to help protect against the flu and reduce complications. ^{1 3 4 6 7}

Who Is on the Research Team?

Michael B Drummond, MD

Principal Investigator

University of North Carolina, Chapel Hill

Are You a Good Fit for This Trial?

This trial is for adults over 40 with COPD, who've had two or more flare-ups in the past year requiring treatment. They must have stable blood pressure and oxygen levels, no recent tobacco use, and not be on certain medications like nasal steroids or immunosuppressants. People with asthma, recent respiratory infections, or those who can't avoid contact with immunocompromised individuals after vaccination are excluded.

Inclusion Criteria

If you are in the healthy control group, your blood pressure should be between 90/55 and 160/90.

I do not have any nasal symptoms according to a questionnaire.

Individual in the healthy control group must complete informed consent

Exclusion Criteria

I was hospitalized due to COVID-19.

You have had severe allergic reactions to certain things in the past.

I have not used any chronic immunosuppression medication in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Enrollment

Baseline assessment of nasal inflammatory state and collection of nasal and blood samples

1 day

1 visit (in-person)

Treatment

Participants receive the nasal influenza vaccine and undergo nasal and blood sampling on specified days

3 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LAIV

Trial Overview The study tests how a live attenuated influenza vaccine (LAIV) affects the nasal immune response in people with COPD. It compares those who frequently have exacerbations to those who don't by measuring cytokines, immune cells in the nose, and viral replication markers following LAIV exposure.

How Is the Trial Designed?

Group I: Healthy Control Experimental Treatment 1 Intervention

Individuals with spirometry-confirmed normal lung function and no asthma history

Group II: COPD Infrequent Exacerbators Experimental Treatment 1 Intervention

Individuals with less than two episodes of worsening in COPD symptoms requiring treatment with antibiotics and/or steroids in the prior 12 months

Group III: COPD Frequent Exacerbators Experimental Treatment 1 Intervention

Individuals with two or more episodes of worsening in COPD symptoms requiring treatment with antibiotics and/or steroids in the prior 12 months

LAIV is already approved in United States, European Union, Canada for the following indications:

Approved in United States as FluMist for:

• Prevention of influenza A and B in individuals 2 through 49 years of age

Approved in European Union as Fluenz for:

• Prevention of influenza A and B in children and adolescents from 24 months to less than 18 years of age

Approved in Canada as FluMist for:

• Prevention of influenza A and B in individuals 2 through 59 years of age

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a study involving 198 patients with cystic fibrosis who received the live-attenuated intranasal influenza vaccine (LAIV), there was a higher risk of reporting serious adverse events (SAEs) and solicited symptoms within the first 6 days post-vaccination, but most were not causally related to the vaccine and were short-lived.

Importantly, the study found no increase in the frequency of antibiotic prescriptions for respiratory conditions following LAIV administration, indicating that the vaccine does not lead to more severe respiratory issues in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events following live-attenuated intranasal influenza vaccination of children with cystic fibrosis: Results from two influenza seasons. Boikos, C., Joseph, L., Scheifele, D., et al.[2018]

In a study of 125 patients with COPD, influenza vaccination resulted in a 27% rate of local adverse reactions, significantly higher than the 6% in the placebo group, but systemic reactions were similar between both groups (76% vs. 81%).

The vaccination did not lead to significant changes in lung function, dyspnoeic symptoms, or exercise capacity, nor did it increase the incidence of acute respiratory illness, indicating that it is safe for patients with COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects associated with influenza vaccination in patients with COPD: a randomized controlled study. Wongsurakiat, P., Maranetra, KN., Gulprasutdilog, P., et al.[2006]

Inactivated influenza vaccines significantly reduced the number of exacerbations in people with COPD, particularly late exacerbations occurring three or more weeks after vaccination, based on data from 11 RCTs involving 6750 participants, with 2469 specifically having COPD.

While there were more mild and transient local adverse reactions reported in vaccinated individuals, there was no evidence of increased early exacerbations or mortality associated with the vaccination, indicating that the benefits of vaccination may outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influenza vaccine for chronic obstructive pulmonary disease (COPD). Kopsaftis, Z., Wood-Baker, R., Poole, P.[2022]

In a study of 153 patients with chronic obstructive pulmonary disease (COPD), combined vaccination with the pneumococcal vaccine (PCV13) and the influenza vaccine significantly reduced clinical impairment and stabilized respiratory function compared to those vaccinated with only the pneumococcal vaccine.

The dual vaccination approach not only lowered the risk of adverse events and hospitalizations due to exacerbations but also resulted in substantial cost savings for the healthcare system, averaging 80-83% per year per patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Analysis of the effectiveness of joint or sequential vaccination with pneumococcal and influenza vaccines in patients with chronic obstructive pulmonary disease]. Ignatova, GL., Antonov, VN., Blinova, EV.[2020]

Influenza vaccination is crucial for individuals with serious medical conditions like COPD, as it significantly reduces the risk of illness, hospitalization, and death associated with influenza infections.

Despite limited specific studies on COPD patients, there is sufficient evidence to recommend annual inactivated influenza vaccinations for this group to improve their quality of life and decrease healthcare costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influenza: the virus and prophylaxis with inactivated influenza vaccine in "at risk" groups, including COPD patients. Hovden, AO., Cox, RJ., Haaheim, LR.[2021]

In a study of older adults with chronic obstructive pulmonary disease (COPD) in Ontario, Canada, the seasonal influenza vaccine was associated with a 22% reduction in hospitalizations due to laboratory-confirmed influenza, indicating its effectiveness in this vulnerable population.

When accounting for potential misclassification of vaccination status, the effectiveness of the vaccine increased to 43%, highlighting the importance of vaccination while also suggesting a need for improved vaccine formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influenza Vaccine Effectiveness in Preventing Hospitalizations in Older Patients With Chronic Obstructive Pulmonary Disease. Gershon, AS., Chung, H., Porter, J., et al.[2021]

Influenza vaccination significantly reduces exacerbations in COPD patients, particularly those with severe airflow limitation (FEV1 < 50%), and shows a trend towards reducing hospitalizations.

The study analyzed data from 2831 COPD patients and found no significant impact of vaccination on all-cause mortality, highlighting the importance of vaccination in preventing complications rather than affecting overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of influenza vaccination on clinical outcomes of chronic obstructive pulmonary disease: A systematic review and meta-analysis. Bao, W., Li, Y., Wang, T., et al.[2021]

Influenza vaccination in COPD patients showed a moderate effectiveness of 40% in preventing laboratory-confirmed influenza during the current season, based on a study of 1761 patients over multiple seasons in Spain.

Increasing influenza vaccination coverage among COPD patients could prevent approximately 13.7% of influenza cases, highlighting the importance of vaccination in reducing exacerbations and improving health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic obstructive pulmonary disease and influenza vaccination effect in preventing outpatient and inpatient influenza cases. Martínez-Baz, I., Casado, I., Navascués, A., et al.[2022]

The study found that the bivalent live attenuated influenza A virus vaccine (CAV) was safe for use in individuals with COPD when administered alongside the trivalent inactivated influenza virus vaccine (TVV).

Participants showed a significant increase in mucosal immune responses, specifically anti-HA immunoglobulin A (IgA) antibodies, after receiving both CAV and TVV, suggesting that the combination may enhance immune protection compared to TVV alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influenza virus vaccination of patients with chronic lung disease. Gorse, GJ., Otto, EE., Daughaday, CC., et al.[2019]

Influenza vaccination significantly reduces the incidence of influenza-related acute respiratory illness (ARI) in patients with COPD, showing a vaccine effectiveness of 76% overall and up to 85% in patients with severe COPD.

While the vaccine is effective against influenza-related ARI, it does not prevent other types of ARI, indicating that vaccination is crucial for COPD patients to specifically guard against influenza complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute respiratory illness in patients with COPD and the effectiveness of influenza vaccination: a randomized controlled study. Wongsurakiat, P., Maranetra, KN., Wasi, C., et al.[2019]

FluMist is an effective intranasal vaccine for preventing influenza A and B, showing good tolerance in healthy individuals aged 5-49 years based on clinical trials.

The vaccine offers a painless alternative to traditional injections, although barriers such as patient eligibility, cost, and insurance coverage may affect its acceptance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influenza vaccination for the pediatric patient: a focus on the new intranasal, cold-adapted, live attenuated vaccine. Ellis, JM., Reilly, JC., Salazar, JC.[2021]

FluMist, a live-attenuated influenza vaccine, maintains genetic and phenotypic stability during its manufacturing process, ensuring that critical mutations for cold adaptation, temperature sensitivity, and attenuation are preserved.

Full genome sequencing of multiple influenza strains showed that all vaccine intermediates retained their essential characteristics, confirming the vaccine's safety and efficacy in providing protection against influenza.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic stability of live, cold-adapted influenza virus components of the FluMist/CAIV-T vaccine throughout the manufacturing process. Buonagurio, DA., Bechert, TM., Yang, CF., et al.[2008]

In a study of 88 patients with chronic obstructive pulmonary disease (COPD), a single dose of the trivalent seasonal influenza vaccine (TIV) resulted in 100% seropositive rates for all influenza strains tested, indicating strong immune response.

The study found high seroprotection rates (over 93%) and significant increases in antibody levels after vaccination, supporting the recommendation for influenza vaccination in COPD patients to help protect them from influenza and its complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity of trivalent seasonal influenza vaccine in patients with chronic obstructive pulmonary disease. Li, Y., Ma, Y., An, Z., et al.[2023]

Citations

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Live, Attenuated Influenza Vaccine Safety in Asthmatic ... The authors concluded that there was little-to-no difference in patient-important safety outcomes between the vaccines in 86.7% of patients with ...