Nasal Bacteria Transfer for Neonatal Infections

Overseen By Danielle Koontz

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Johns Hopkins University

Disqualifiers: S. aureus colonization, Immunodeficiency, Respiratory illness, others

Compensation: Varies

Number of Visits: 6

Duration: 1 day

175 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to protect newborns in the NICU from infections by transferring beneficial bacteria from a parent's nose to the baby's nose. Researchers aim to determine if this transfer, known as Nasal Microbiota Transplant (NMT), can increase the variety of good bacteria in babies, potentially boosting their health. The trial includes three groups: one receives a single transfer, another receives multiple transfers, and the last receives a placebo (a harmless substitute). Suitable candidates for this trial are newborns staying in the NICU for more than a week, who are not currently carrying the specific bacteria S. aureus, and have a parent without recent cold or flu symptoms. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that this Nasal Microbiota Transplant is safe for neonates?

Research is exploring whether Nasal Microbiota Transplant (NMT) can safely increase bacterial diversity in a newborn's nose. Early studies have examined how a parent's nasal bacteria might transfer to their baby to aid this diversity. These initial findings suggest that NMT is generally well-tolerated, but limited safety data is available due to the study's early stage.

More advanced research in similar areas, such as microbiota transplants for other conditions, has shown these procedures can be safe. However, because this is a new application, monitoring for side effects is crucial. For those considering participation in such a trial, the research is designed to closely monitor for any issues and ensure optimal safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about using Nasal Microbiota Transplant (NMT) for neonatal infections because it introduces beneficial bacteria directly from a parent's nose to their newborn. Unlike traditional antibiotics that target and kill bacteria indiscriminately, NMT aims to build a healthy bacterial environment in the baby's nasal passages, potentially preventing infections naturally. This method could offer a more targeted approach to fostering a protective microbiome, reducing the need for antibiotics, and possibly decreasing antibiotic resistance. Additionally, the process is quick and non-invasive, involving just a simple swab, making it an appealing option for newborns.

What evidence suggests that this trial's treatments could be effective for neonatal infections?

Research shows that nasal microbiota transplantation (NMT) could help treat conditions like chronic rhinosinusitis by introducing beneficial bacteria to the nose. Studies have found that NMT can increase bacterial diversity in the nose, which is linked to better health. In this trial, some newborns will receive a Single NMT, while others will receive a Repeat NMT. A wide range of nasal bacteria might protect newborns from infections. Although specific data on newborns remains limited, transferring bacteria from a parent to a child could enhance the child's bacterial diversity. Early results appear promising, but further research is needed to confirm these benefits for newborns. ^{4 6 7 8 9}

Who Is on the Research Team?

Aaron Milstone

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for newborns at risk of nasal infections. It's testing if a parent-to-child nasal microbiota transplant (NMT) can transfer healthy bacteria from parents to their baby to boost the baby's immune system.

Inclusion Criteria

Parent/Adult provider is able to provide informed consent

Neonate has anticipated NICU length of stay > 7 days

Neonate is not colonized with S. aureus on baseline screening

Exclusion Criteria

Parent/adult provider tests positive on baseline screening test for a respiratory pathogen

Parent/adult provider is not able to provide written informed consent

Parent/adult provider had positive COVID-19 test in prior 21 days

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Eligible neonates undergo a nasal microbiota transplant (NMT) from parent to child

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

5 visits (in-person) on Day 2, 4, 7, 10, 14

What Are the Treatments Tested in This Trial?

Interventions

• Nasal Microbiota Transplant (NMT)

Trial Overview The study compares two groups: one receives a single NMT, while the other gets repeated NMTs. The goal is to see which method better increases the diversity of good bacteria in babies' noses.

How Is the Trial Designed?

Group I: Single NMT Experimental Treatment 1 Intervention

Swab parent nares then insert swab directly into neonate nares once.

Group II: Repeat NMT Experimental Treatment 1 Intervention

Swab parents nares then insert swab directly into neonate nares multiple times.

Group III: Placebo Placebo Group 1 Intervention

Insert a sterile swab into neonate nares.

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Published Research Related to This Trial

In children with purulent nasopharyngitis (NPT), the presence of potential respiratory pathogens like Streptococcus pneumoniae and Haemophilus influenzae increases, while beneficial organisms that could inhibit these pathogens are often absent.

Current evidence suggests that using antibiotics may not effectively shorten the duration of NPT, indicating a need for careful consideration in the management of this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microbial dynamics of purulent nasopharyngitis in children. Brook, I.[2019]

The study analyzed the nasal microbiota of 122 infants over 18 months, revealing that infants with rhinitis showed a decrease in bacterial diversity compared to healthy controls, suggesting a potential link between microbiome development and respiratory issues.

Specific bacterial families, such as Oxalobacteraceae and Aerococcaceae, were more abundant in infants with rhinitis and wheeze, while healthy infants had higher levels of Corynebacteriaceae, indicating that the composition of the nasal microbiome may influence susceptibility to respiratory disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Establishment of the nasal microbiota in the first 18 months of life: Correlation with early-onset rhinitis and wheezing. Ta, LDH., Yap, GC., Tay, CJX., et al.[2022]

The study will involve 20 healthy pregnant women who will receive a nasal inoculation of Neisseria lactamica to investigate if this leads to neonatal colonization after birth, potentially reducing the risk of Neisseria meningitidis infections in infants.

Safety and microbiome evolution will be assessed through various sample collections over one month postpartum, with the study approved by the ethics committee, indicating a structured approach to understanding the impact of maternal microbiota on infant health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlled human infection with Neisseria lactamica in late pregnancy to measure horizontal transmission and microbiome changes in mother-neonate pairs: a single-arm interventional pilot study protocol. Theodosiou, AA., Laver, JR., Dale, AP., et al.[2023]

Fecal Microbiota Transplantation (FMT) administered by enema significantly reduced intestinal inflammation and improved histological damage in a mouse model of Necrotizing Enterocolitis (NEC), suggesting it may be an effective treatment strategy.

In contrast, FMT given by gavage worsened inflammation and did not improve the condition, highlighting the importance of the method of administration in the efficacy of FMT for NEC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation by enema reduces intestinal injury in experimental necrotizing enterocolitis. Liu, J., Miyake, H., Zhu, H., et al.[2020]

Fecal microbiota transplantation (FMT) is highly effective for treating Clostridium difficile infection (CDI), with a 90% resolution of diarrhea reported in 867 patients across 33 studies, and a 94% resolution after repeated FMT in a randomized controlled trial with 16 participants.

FMT shows promise in treating ulcerative colitis, with remission rates varying from 0% to 68% in 106 patients, while its efficacy in Crohn's disease, chronic constipation, pouchitis, and irritable bowel syndrome remains inconclusive due to limited data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review. Rossen, NG., MacDonald, JK., de Vries, EM., et al.[2022]

In patients with allergic rhinitis (AR), the nasal microbiome showed a higher dominance of Staphylococcus species, particularly Staphylococcus aureus and Staphylococcus epidermidis, which may influence allergic responses.

Staphylococcus aureus from AR patients was found to reduce levels of IL-33, a key cytokine involved in allergic inflammation, suggesting that this nasal commensal can mediate anti-allergic effects and modulate Th2 inflammation in allergic rhinitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Symbiotic microbiome Staphylococcus aureus from human nasal mucus modulates IL-33-mediated type 2 immune responses in allergic nasal mucosa. Jeon, YJ., Gil, CH., Won, J., et al.[2021]

Faecal microbiota transplantation (FMT) is being established as a safe second-line treatment for recurrent Clostridium difficile infections, with a comprehensive framework developed to ensure donor screening and clinical application comply with the European Tissue Act.

The framework includes rigorous donor recruitment and screening processes, laboratory protocols for processing faecal samples, and a structured follow-up system to monitor patient outcomes, ensuring safety and traceability in FMT procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Faecal microbiota transplantation: establishment of a clinical application framework. Jørgensen, SMD., Hansen, MM., Erikstrup, C., et al.[2022]

A study of 58 children aged 4 to 7 years found that distinct nasopharyngeal microbiota structures are linked to the risk of upper respiratory infections (URI) and sinusitis, with four different microbiota clusters identified.

Children with a nasopharyngeal microbiota dominated by Moraxella (Cluster I) had a significantly increased risk of URI and sinusitis, suggesting that the composition of nasal bacteria can influence respiratory health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moraxella-dominated pediatric nasopharyngeal microbiota associate with upper respiratory infection and sinusitis. McCauley, KE., DeMuri, G., Lynch, K., et al.[2022]

Hospitalized neonates who did not acquire Staphylococcus aureus nasal colonization had a higher abundance of beneficial bacterial species that can help prevent S. aureus colonization, suggesting a protective role of the nasal microbiota.

After treatment with intranasal mupirocin, cases showed an increase in Rothia mucilaginosa, indicating that certain bacteria may thrive post-treatment, which could influence future strategies for preventing S. aureus infections in vulnerable infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Association Between the Developing Nasal Microbiota of Hospitalized Neonates and Staphylococcus aureus Colonization. Khamash, DF., Mongodin, EF., White, JR., et al.[2022]

Fecal microbiota transplantation (FMT) is a generally safe and well-tolerated procedure for treating recurrent Clostridioides difficile infections, even in high-risk patients, with most short-term risks being mild and related to delivery methods.

Recent concerns have emerged regarding serious adverse events linked to FMT products from stool banks that do not screen for multi-drug resistant organisms, highlighting the need for improved safety protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation: Is It Safe? Park, SY., Seo, GS.[2021]

In a long-term follow-up study of 84 patients (45 receiving faecal microbiota transplantation (FMT) and 39 receiving antibiotics), FMT was found to be a safe and effective treatment for recurrent C. difficile infection, with no significant differences in severe disease incidence between the two groups over an average of 3.8 years.

Patients who received FMT reported significantly faster improvements in bowel habits and better mental health compared to those treated with antibiotics, indicating that FMT may offer additional benefits beyond just treating the infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The long-term effects of faecal microbiota transplantation for gastrointestinal symptoms and general health in patients with recurrent Clostridium difficile infection. Jalanka, J., Hillamaa, A., Satokari, R., et al.[2022]

Citations

1. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/alr.23122

Upper airway microbiome transplantation for patients with ... Two hundred and four species were common to all groups and termed core microbiota. Species identified in more than one group, but not all, were ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36515012/

Upper airway microbiome transplantation for patients with ... Outcome measures were 22-item Sino-Nasal Outcome Test (SNOT-22) ... MeSH terms. Anti-Bacterial Agents / therapeutic use; Chronic Disease; Humans; Microbiota* ...

3. withpower.com withpower.com/trial/phase-1-staphylococcus-aureus-4-2024-a1eb9

Nasal Bacteria Transfer for Neonatal Infections The study analyzed the nasal microbiota of 122 infants over 18 months, revealing that infants with rhinitis showed a decrease in bacterial diversity compared to ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0966842X24003263

Nasal microbiota transplantation: a gateway to novel ... Two recent studies have highlighted the potential of nasal microbiota transplantation (NMT) to treat chronic rhinosinusitis (CRS).

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03122795

Sinonasal Microbiome Transplant as a Therapy for Chronic ... A number of studies aimed at investigating the microbiota of the nose and paranasal sinuses in health and disease has been published with very varying outcomes.

6. academic.oup.com academic.oup.com/ofid/article/11/11/ofae644/7848525

Association of Neonatal and Maternal Nasal Microbiome ... This preliminary study characterized the biodiversity of nasal microbiota comparing neonates in the neonatal intensive care unit and their mothers.

7. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05695196/feasibility-and-safety-study-of-parent-to-child-nasal-microbiota-transplant

Feasibility and Safety Study of Parent-to-Child Nasal ... This feasibility and safety pilot study looks to determine whether transferring a parents healthy, diverse nasal microbiota to the participant's infant(s) will ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06283355?cond=Parents+and+Children&aggFilters=status%3Arec

Comparing Single Versus Repeat NMT on the Diversity of ... This study aims to determine whether a parent-to-child nasal microbiota transplant (NMT) can seed and engraft parental organisms into the ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2590097825000345

Nasal–Gut Microbiome Axis in Health and Disease A relatively nascent but promising concept is the nasal-gut microbiome axis, which posits that interactions between the nasal and gut microbiota ...