No registrations found.
ID
Source
Brief title
Health condition
COVID-19
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoints: We investigated whether inhalation of enoxaparin by human study participants blocks binding of SARS-CoV-2 to human nasal epithelial cells. Binding of both SARS-CoV-2 pseudovirus (pg/mL) and the authentic virus, hCoV-19/Italy (TCID/ml) to nasal epithelial cells obtained from volunteers after their nasal cavity was exposed to either LMWH enoxaparin or placebo (saline NaCl 0,9%).
Pseudovirus binding was detected by p24 ELISA whereas authentic SARS-CoV-2 binding was detected by RT-PCR measurement of ORF1b/GAPDH.
Timepoints: Virusbinding happens on the same day as cells are obtained from study participants to ensure maximum viability of cells, virus exposure happens for 4 hours at 4C after which all cells are lysed to prevent further infection.
Secondary outcome
Secondary endpoints: We characterized the nasal cell populations and the effect on inhalation on lymphocyte influx, as well as on expression of ACE-2 and heparan sulfates. We investigated the effectiveness of inhalation of enoxaparin by comparing inhalation with in vitro addition of enoxaparin prior to SARS-CoV-2 binding.
Timepoints: Phenotyping happens the same day that cells are obtained from study participants to ensure maximum viability of cells.
Background summary
SARS-COV-2 utilise various receptors on the human cell surface to facilitate virus-binding and cellular entry. While angiotensin converting enzyme 2 (ACE-2) has been known for a long time little is understood about other receptors. Syndecans are transmembrane receptors that have, according to published work in the AMC, a role in viral-binding and cellular infection similar to ACE-2 (for SARS-CoV-2 they are required as a co-receptor for infection via ACE-2). Syndecans are (made up of) heparansulfates, which provides with an interesting mechanism for potential virus block.
Low molecular weight heparins (LMWHs), which have been extensively used in the clinic as anticoagulants are chemically speaking very similar. Previous (unpublished) works by the department of experimental immunology in the AMC Amsterdam has shown that on cell lines LMWHs can be used to prevent virusbinding by SARS-CoV-2 through competitive agonism.
We hypothesise that LMWHs can offer a similar protection in vivo when applied to the nasal epithelium, thereby providing an effective, cheap and safe prevention against infection from SARS-CoV-2, or similar virusses.
Study objective
Low molecular weight heparins able to block virusbinding from SARS-CoV-2 ex-vivo through competitive agonism, our hypothesis is that applying LMWHs using a spray to the nasal epithelium offers similar protection as has been previously observed in primary cells and cell lines.
Study design
Medication is given sequentially every 10 minutes over a period of 30 minutes.
Cells are withdrawn after 30 minutes, stored in medium to keep the populations healthy and brought to a BSL-3 lab where virus exposure occurs. Viral binding occurs for 4 hours after which all cellular material is lysed to prevent further binding.
Intervention
Intervention medication: 4500IE enoxaparin (in 300uL solution)
Control medication: NaCl 0,9% (in 300uL water)
Inclusion criteria
In order to be eligible for participation, a participant must:
- be able to provide written informed consent (Verbal informed consent or deferred informed concent will be used for the initial screening visit, where written informed consent will be obtained).
- be physically healthy (as defined by not suffering from any illness or disease obstructing general daily functioning)
- be aged between 18 – 65 years
- be sufficiently well versed in the Dutch language, subject to the opinion of the Investigator
Exclusion criteria
If any of the following apply to someone wishing to participate, he/she is rendered ineligible for participation, a participant:
- is unlikely to comply with study procedures, as deemed by the recruiting research doctor/nurse
- has mental disorders that in the view of the investigator would interfere with adherence to study procedures or might impair a decision to participate in the study
- has a known allergy or intolerance to LWWH or heparine-related products, as well as a medical history of heparine inducted thrombocytopenia (HIT).
- has any relevant clinical medical condition that is in the opinion of the investigator to make a volunteer unsuitable for participation in the study (under which underlying haematological disorders or bleeding disorder.
- has (anamnestic) evidence of a respiratory infection in the 4 weeks prior to enrolment.
- has a tympanic temperature exceeding 38,5 degrees Celsius during the screening and clinical visits.
- has frequent nosebleeds (>1/ month).
Design
Recruitment
IPD sharing statement
Plan description
Anonymised viral binding data will be displayed using a patient trial number to, in published data, compare cells treated with enoxaparin or placebo medication.
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL9430 |
| Other | METC AMC : METC 2020_223 |