Topical Antibacterial Agents for Prevention of COVID-19

Study Overview
=================
Brief Summary
-----------------
The primary objective of this study is to determine whether intranasal application of aminoglycoside (Neosporin) increases local nasal innate immune responses compared to placebo control in healthy participants.

Detailed Description
-----------------
The primary objective of this study is to determine whether intranasal application of aminoglycoside (Neosporin) increases local nasal innate immune responses compared to placebo control in healthy participants. This study will evaluate the role of nasally applied neomycin at inducing local antiviral interferon responses that have been associated with protection against SARS-CoV2 ( severe acute respiratory syndrome coronavirus 2). Local interferon immune responses including the nasal compartment are important in driving early protective responses against the virus. Given the current challenges with vaccine access in lower- and middle-income countries (LMIC) as well as varying vaccine acceptance and hesitancy, additional strategies are needed to help curb the spread of SARS-CoV2. There is a need for easily available agents that are low cost and effective at decreasing the effects of SARS-CoV2 exposure. The investigators will evaluate the effectiveness of intranasal Neosporin (which contains neomycin) at inducing interferon responses in human subjects. This will be a proof of concept that such approach will provide local immune response that could be beneficial against the SARS-CoV2 infection. The potential impact of this study is the utilization of existing and available topical medications for the purpose of providing local prophylaxis against SARS-CoV2. The overall hypothesis is that neomycin containing agents such as Neosporin when applied topically in the nose can induce local antiviral interferon responses in adult human subjects. Neosporin will be compared to placebo, control Vaseline (Unilever) or equivalent. A run-in cohort of 6 participants to test optimal sampling and storage conditions will be used. The focus of this study is the randomized double-blinded placebo-controlled trial. The study will enroll an estimated 40 healthy subjects at one study site, Yale University. Local nasal immune responses will be measured using RT-PCR and multiplex ELISA for interferon response. Participants will apply a small amount of the cream (less than a pea size) to the inside of both nostrils, then pinch the nose to spread the cream. Participants will use Neosporin or placebo twice a day for 7 days.

Official Title
-----------------
Topical Antibacterial Agents for Prevention of COVID-19

Conditions
-----------------
COVID-19, SARS-CoV2 Infection

Intervention / Treatment
-----------------
* Drug: Neosporin
* Other: Vaseline


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Completion of written informed consent Covid-negative within 48 hours of enrollment based on PCR or Antigen test. If subjects are found to be positive, the PI will recommend appropriate follow-ups. In good general health as evidenced by medical history Ability to take Nasal medication and be willing to adhere to the nasal agent regimen Exclusion Criteria: Participant with active nasal or respiratory symptoms. Participant with active or chronic respiratory nasal or respiratory infections and or is currently on antibiotics Participant who has been treated with oral or topical antibiotics with the past 14 days Participant who is on intranasal or oral corticosteroids or systemic immunosuppression medication Participant who has immunocompromised conditions such as rheumatological diseases, HIV, cancer on chemotherapy or biologic therapies. Participant who is on any intranasally applied medications (prescription or over the counter) including nonmedical nasal products and the use of Netipot or other nasal flush products. Participant with known allergic history to Neosporin (allergic history to neomycin or bacitracin or polymyxcin or pramoxine or the inactive ingredients that include cocoa butter, cottonseed oil, olive oil, sodium pyruvate, tocopheryl acetate and white petrolatum) Participant with known allergies to aminoglycoside antibiotics (neomycin, tobramycin, gentamycin, others) Participant with history of COVID-19 infection in the past 8 weeks. Participant who is pregnant

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Run-in cohort to test optimal sampling and storage conditions: For 6 participants, the investigator will test 50:50 with Neosporin vs Placebo participant nasal sampling and shipping protocol to evaluate signal to noise of interferon-stimulated genes (ISG) measures. If needed, we will rerun the power calculations.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neosporin<br>Neosporin will be distributed by the Yale Investigational Pharmacy. Subjects are to use Neosporin twice a day for 7 days. | Drug: Neosporin<br>* Neosporin is neomycin, bacitracin and polymyxin B with formulation 3.5mg/400 units/5,000 units. The subject will self-apply a small amount (approximately 0.5 g) of the ointment topically into each nostril (intranasal) twice daily (morning and evening) for seven days. Subjects are to pinch the nose to spread the cream.<br>|
| Placebo Comparator: Vaseline or equivalent<br>Vaseline or equivalent will be distributed by the Yale Investigational Pharmacy. Subjects are to use Vaseline twice a day for 7 days. | Other: Vaseline<br>* The subject will self-apply a small amount (approximately 0.5 g) of the ointment topically into each nostril (intranasal) twice daily (morning and evening) for seven days. Subjects are to pinch the nose to spread the cream.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in in interferon response profile from nasal samples collected measured by a multiplex ELISA assay | Measurement of interferon response from samples collected using a multiplex ELISA to detect which interferon-stimulated genes (ISGs) are present in sample. ISGs measured include Irf7, Oas1a, Oasl2, Cxcl9, and CxcL10 as well as other corresponding interferons such as Ifna, ifnb, and ifnl | From baseline up to Month 1 | 
| Change in in interferon response gene expression profile from nasal samples collected measured by RT-PCR | Measurement of interferon response from samples collected using RT-PCR to detect expression of ISGs. ISGs measured include Irf7, Oas1a, Oasl2, Cxcl9, and CxcL10 as well as other corresponding interferons such as Ifna, ifnb, and ifnl | From baseline up to Month 1 | 
| Change in RNA expression profile of ISGs using RNAseq assay | In a subset of subjects in both arms, RNAseq will be performed to assess the presence and quantity of RNA on samples collected at Day 1 and Day 8. ISGs assessed include Irf7, Oas1a, Oasl2, Cxcl9, and CxcL10 as well as other corresponding interferons such as Ifna, ifnb, and ifnl | Day 1and Day 8 | 
| Change in RNA expression profile of ISGs using single cell RNAseq assay | In a subset of subjects in both arms, single cell RNAseq will be performed to assess the presence and quantity of RNA on single cells from samples collected at Day 1 and Day 8. ISGs assessed include Irf7, Oas1a, Oasl2, Cxcl9, and CxcL10 as well as other corresponding interferons such as Ifna, ifnb, and ifnl | Day 1 and Day 8 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Neosporin, Antibacterial agent, intranasal application