Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04475120 |
| Other study ID # |
4220 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2/Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
April 15, 2020 |
| Est. completion date |
July 2, 2020 |
Study information
| Verified date |
May 2021 |
| Source |
University of Rome Tor Vergata |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
COVID-19 is considered an ongoing international global health problem which already caused 12
million confirmed cases. No specific effective treatment has been identified so far, and
available supportive therapies are intended just to severe patients. Asymptomatic and mildly
symptomatic patients remain a transmission reservoir, with possible evolution to the most
severe disease form, without a clear treatment indication.
Lactoferrin (Lf) is a multifunctional glycoprotein, belonging to transferrin family, secreted
by exocrine glands and neutrophils and present in all human secretion. The pleiotropic
activity of Lf is mainly based on its four different functions: chelate two ferric iron per
molecule, interact with anionic molecules, enter inside nucleus and modulate iron
homeostasis. The ability to chelate two ferric ions per molecule is associated to the
inhibition of reactive oxygen species formation as well as this sequestration of iron,
pivotal for bacterial and viral replication, is at the basis of its antibacterial and
antiviral activity. Moreover, Lf exerts its antiviral activity against the majority of the
tested viruses by binding to heparan sulphate, while against few viruses by interacting with
surface components of viral particles. The capability of Lf to exert antiviral activity, by
binding to host cells or viral particles or both, strengthens the idea that this glycoprotein
is "an important brick in the mucosal wall, effective against viral attacks". Lf was able to
block the binding of the spike protein to host cells, indicating that Lf exerted its
inhibitory function at the viral attachment stage. The current accepted model suggests that
Lf could block viral entry by interacting with heparan sulfate proteoglycans (HSPGs), which
mediate the transport of extracellular virus particles from the low affinity anchoring sites
to the high affinity specific entry as ACE-2.
Investigators performed a prospective, interventional pilot study to assess the efficacy of
liposomal lactoferrin in COVID-19 patients with mild-to moderate disease and in COVID-19
asymptomatic patients.
Secondary objectives evaluated the safety and tolerability of liposomal lactoferrin for oral
and intra-nasal use.
Description:
COVID-19 is considered an ongoing international global health problem which already caused 12
million confirmed cases. No specific effective treatment has been identified so far, and
available supportive therapies are intended just to severe patients. Asymptomatic and mildly
symptomatic patients remain a transmission reservoir, with possible evolution to the most
severe disease form, without a clear treatment indication.
Lactoferrin (Lf) is a multifunctional glycoprotein, belonging to transferrin family, secreted
by exocrine glands and neutrophils and present in all human secretion. The pleiotropic
activity of Lf is mainly based on its four different functions: chelate two ferric iron per
molecule, interact with anionic molecules, enter inside nucleus and modulate iron
homeostasis. The ability to chelate two ferric ions per molecule is associated to the
inhibition of reactive oxygen species formation as well as this sequestration of iron,
pivotal for bacterial and viral replication, is at the basis of its antibacterial and
antiviral activity.
Moreover, Lf exerts its antiviral activity against the majority of the tested viruses by
binding to heparan sulphate, while against few viruses by interacting with surface components
of viral particles. The capability of Lf to exert antiviral activity, by binding to host
cells or viral particles or both, strengthens the idea that this glycoprotein is "an
important brick in the mucosal wall, effective against viral attacks". Lf was able to block
the binding of the spike protein to host cells, indicating that Lf exerted its inhibitory
function at the viral attachment stage. The current accepted model suggests that Lf could
block viral entry by interacting with heparan sulfate proteoglycans (HSPGs), which mediate
the transport of extracellular virus particles from the low affinity anchoring sites to the
high affinity specific entry as ACE-2.
Investigators performed a prospective, interventional, pilot study to assess the efficacy of
liposomal lactoferrin in COVID-19 patients with mild-to moderate disease and in COVID-19
asymptomatic patients.
Secondary objectives evaluated the safety and tolerability of liposomal lactoferrin for oral
and intra-nasal use.
Investigators conducted a parallel 3 group clinical trial to investigate the effect and
tolerability of a liposomal bLf formulation as a supplementary nutraceutical agent in COVID19
patients. A total of 92 COVID19 patients, 25/92 asymptomatic and 67/92 mild-to-moderate, were
recruited and divided into 3 groups according to the administered regimen: 32/92 COVID-19
patients, 14 hospitalised and 18 in home-based isolation, received oral and intranasal
liposomal bLF supplement; 32 COVID-19 hospitalised patients were treated with
hydroxychloroquine, azitromicin and lopinavir/darunavir as standard of care treatment (SOC);
twenty eight COVID-19 patients, in home-based isolation did not take any medication against
COVID-19. Furthermore, a group of 32 healthy subjects with negative COVID19 rRT-PCR was added
as a control group for ancillary analysis.
Thirty-two patients (14 hospitalised and 18 in home-based isolation) belonging to the first
group received oral and intranasal liposomal bLf. BLf capsules for oral use containing 100 mg
of bLf encapsulated in liposome while bLf nasal spray had about 8 mg/ml of bLf encapsulated
in liposome. BLf, contained in both products, was tested by SDS-PAGE and silver nitrate
staining and its purity was about 95%. The bLf iron saturation was about 5% as detected via
optical spectroscopy at 468 nm based on an extinction coefficient of 0.54 (100% iron
saturation, 1% solution). The scheduled dose treatment of liposomal bLf for oral use was 1gr
per day for 30 days (10 capsules per day) in addition to the same formulation intranasally
administered 3 times daily (a total of about 16 mg/nostril) Thirty-two hospitalized patients
belonging to the second group were only treated with SOC regimen according to the national
guidelines at the time of the enrollment: lopinavir/ritonavir cps 200/50 mg, 2x2/day
(alternatively darunavir 800 mg 1 cp/day+ritonavir 100 mg 1 cp/day or darunavir/cobicistat
800/150 mg 1 cp/day), chloroquine 500 mg, 1x2/day or hydroxychloroquine cp 200 mg, 1x2/day.
SOC regimen lasted from 5 to 20 days, with timing to be established according to clinical
course.
Twenty-eight patients, in home-based isolation, belonging to the third group did not receive
any therapy.
A control group, comprising 32 healthy volunteers, did not receive any treatment or placebo.
Blood samples and clinical assessments were evaluated at baseline (T0), after 15 days (T1)
and after 30 days (T2).
Eligible patients were over 20 years old, with a confirmed positivity to COVID-19 at the
naso-oro-pharyngeal swab.
Exclusion criteria included pregnant and lactating women, patients taking nitric oxide and
nitrates, patients with reported allergy to milk proteins, patients with a previous history
of bronchial hyperactivity and patients with pre-existing respiratory diseases.
