Colonization, Asymptomatic Clinical Trial
— SAMSAMOfficial title:
Studying Respiratory Infections and Colonisation in Children Using Daily Minimally-invasive Nasal Sampling
| NCT number | NCT06049537 |
| Other study ID # | P21.067 |
| Secondary ID | |
| Status | Completed |
| Phase | |
| First received | |
| Last updated | |
| Start date | January 21, 2022 |
| Est. completion date | November 27, 2023 |
| Verified date | December 2023 |
| Source | Leiden University Medical Center |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Observational |
Rationale: Respiratory tract infections (RTI) are a major cause of morbidity in young children in high- income countries and the major cause of mortality in developing countries. Causative bacteria and viruses are regular residents of the nasopharynx of asymptomatic individuals (colonization) and live there together with other presumed harmless commensals, without causing disease. These non-pathological infections/colonization episodes are important for transmission, intermediate step to disease and boost immune responses. The investigators recently validated the use of minimally-invasive nasal sampling methods that can be done at home for the study of host and microbial parameters in adults and children. In this study the investigators will focus on the daily microbial and immunological composition of the nasopharynx during health in relation to symptoms. Primary objective: Associate acquisition of pneumococcal colonisation with levels of pre-existing polysaccharide specific memory B cells. Secondary objectives include: Validate the use of synthetic absorptive matrices (SAM) for detection of respiratory pathogens versus nasopharyngeal swabs (NPS) and saliva; Assess dynamics of URT infection/colonisation and examine its relationship with symptoms, host responses and microbiota; Measure transmission between children and parents and immune responses in parents. Study design: Prospective community-based cohort study.total of 45 children, aged 1-5 years old attending daycare or (pre-)school, will be included, including a pilot of 10 children to assess tolerability. If there are insufficient pneumococcal acquisitions in the study to assess the primary outcome, additional children can be recruited in groups of 3 or 4 children (up to 10). For a subset of participating children, both parents will be asked to self-collect daily saliva during the study. Primary study parameters: Frequency of systemic polysaccharide specific B cells in children that become colonised during the study versus children that do not become colonised Secondary study parameters: Dynamics of respiratory bacteria and viruses during URT infection/colonisation. Presence and load for bacteria and viruses in children in SAM versus saliva and NPS. Local microbiota and immune profiles and association with infection/colonisation and symptomology. For a subset of parents, daily presence and load of bacteria and viruses as well as host immune factors measured in saliva.
| Status | Completed |
| Enrollment | 46 |
| Est. completion date | November 27, 2023 |
| Est. primary completion date | November 27, 2023 |
| Accepts healthy volunteers | |
| Gender | All |
| Age group | 1 Year to 5 Years |
| Eligibility | Inclusion Criteria: - Written informed consent obtained from all legal representatives, for example both parents. - Child aged 1-5 years of age attending day care, peuterspeelzaal or school at least 2 (half) days a week. - Parents ability and willingness to adhere to protocol-specified procedures, including availability of a freezer at home to store samples. This does not include donation of saliva by parents themselves, which is related to a secondary endpoint. Exclusion Criteria: - History of respiratory tract infections requiring hospitalization - Current use of antibiotics, or antibiotics use in past four weeks - Use of immune-altering medication (such as steroids, including inhaled corticosteroid) - No history of severe concomitant disease (severe congenital heart disease, bronchopulmonary dysplasia, prematurity <32 weeks, cystic fibrosis, sickle cell disease, congenital or acquired immunodeficiency disorders, cardiovascular disease, neuromuscular disorders, oncology patients or major congenital anomalies) |
| Country | Name | City | State |
|---|---|---|---|
| Netherlands | Spaarne Gasthuis | Hoofddorp |
| Lead Sponsor | Collaborator |
|---|---|
| Leiden University Medical Center | Spaarne Gasthuis |
Netherlands,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Frequency of systemic polysaccharide specific B cells in children that become colonised during the study versus children that do not become colonised | up to study completion, 28 or 29 days | ||
| Secondary | The number of participants with pneumococcal colonisation presence over time. | lyta, piab and serotype-specific qPCR | up to study completion, 28 or 29 days | |
| Secondary | Pneumococcal colonisation density over time. | lyta, piab and serotype-specific qPCR | up to study completion, 28 or 29 days | |
| Secondary | The number of participants with presence of other bacteria and viruses | Presence of other respiratory bacteria (such as Haemophilus influenzae and Staphylococcus aureus) and viruses (such as coronaviruses and influenza virus) during URT infection/colonisation, measured by molecular methods. | up to study completion, 28 or 29 days | |
| Secondary | Density of other bacteria and viruses | Density of other respiratory bacteria (such as Haemophilus influenzae and Staphylococcus aureus) and viruses (such as coronaviruses and influenza virus) during URT infection/colonisation, measured by molecular methods. | up to study completion, 28 or 29 days | |
| Secondary | Local microbiome composition measured by 16S | Relative abundance of ASV | up to study completion, 28 or 29 days | |
| Secondary | Nasal and systemic antibodies titres specific for identified pathogens, measured using ELISA or antigen arrays | antigen-specific IgG, IgA and IgM titres | up to study completion, 28 or 29 days | |
| Secondary | Nasal cytokine levels, assessed using multiplex assays such as Luminex | Individual cytokines will be reported in absolute or relative values | up to study completion, 28 or 29 days | |
| Secondary | Symptom questionnaires | Symptoms are scaled on presence/absence | up to study completion, 28 or 29 days | |
| Secondary | Evaluation/Sample tolerability questionnaires | scale includes completely disagree, disagree, neutral, agree, completely agree for each question | day 28, last visit | |
| Secondary | Presence of bacteria and viruses in saliva of a subset of parents on a daily interval | Measured using molecular methods | up to study completion, 28 or 29 days | |
| Secondary | Density of bacteria and viruses in saliva of a subset of parents on a daily interval | Measured using molecular methods | up to study completion, 28 or 29 days |