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Efficacy and Safety of Liposomal Lactoferrin in COVID-19 Patients With Mild-to-Moderate Disease and in COVID-19 Asymptomatic Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04475120
Recruitment Status : Completed
First Posted : July 17, 2020
Last Update Posted : May 14, 2021
Sponsor:
Information provided by (Responsible Party):
Elena Campione, University of Rome Tor Vergata

Brief 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.


Condition or disease Intervention/treatment Phase
Covid19 Drug: liposomal lactoferrin Drug: SOC therapy Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 92 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Interventional Pilot Study to Assess the Use of Oral and Intra-nasal Liposomal Lactoferrin in COVID-19 Patients With Mild-to-Moderate Disease and in COVID-19 Asymptomatic Patients
Actual Study Start Date : April 15, 2020
Actual Primary Completion Date : July 2, 2020
Actual Study Completion Date : July 2, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Liposomal Lacroferrin
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)
Drug: liposomal lactoferrin
oral and intra-nasal formulation

Active Comparator: SOC therapy
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.
Drug: SOC therapy
oral administration

No Intervention: Home-based isolation
Twenty-eight patients, in home-based isolation, belonging to the third group did not receive any therapy.
No Intervention: Healthy volunteers
A control group, comprising 32 healthy volunteers, did not receive any treatment or placebo.



Primary Outcome Measures :
  1. Rate of viral clearance Time to viral clearance [ Time Frame: 30 days ]
    time to naso-oro-pharingeal swab negativization


Secondary Outcome Measures :
  1. Time to clinical improvement [ Time Frame: 30 days ]
    time to improvement of clinical symptoms and blood parameters



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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Eligible patients were over 20years old, with a confirmed positivity to COVID-19 at the oropharyngeal swab

Exclusion Criteria:

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. COVID-19 patients requiring intensive care or mechanical ventilation were excluded.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04475120


Locations
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Italy
University of Rome Tor Vergata
Rome, Italy, 00133
Sponsors and Collaborators
University of Rome Tor Vergata
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Responsible Party: Elena Campione, Associate Professor, University of Rome Tor Vergata
ClinicalTrials.gov Identifier: NCT04475120    
Other Study ID Numbers: 4220
First Posted: July 17, 2020    Key Record Dates
Last Update Posted: May 14, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Study Protocol

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Lactoferrin
Anti-Infective Agents