Clinical trial NCT04526821: Lactoferrin for Prevention of COVID-19 in Health Care Workers
Official title: Bovine Lactoferrin for the Prevention of COVID-19 Infection in Physicians and Nurses in Hospitals in Lima, Peru: a Double Blinded Randomized Clinical Trial (LF-COVID)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: SARS-CoV-2
Keywords: SARS-CoV-2 Infection
Lactoferrin
Health Care Workers
Lead sponsor: Universidad Peruana Cayetano Heredia
Sponsor class: OTHER
Collaborators: name: Hospital Nacional Arzobispo Loayza
First posted: 2020-08-26
Enrollment: 209
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Clinical trial in health care personnel (physicians, nurses or nurse assistants) to determine the effect of orally-administered bovine lactoferrin to prevent SARS-CoV-2 infection. Participants will be randomized to receive daily bovine lactoferrin plus standard measures during 12 weeks or placebo (maltodextrine) for the prevention of SARS-CoV-2. The target enrollment is 336 participants. Each study participant will be monitored twice a week for symptoms of COVID-19 and if symptoms occur, a RT-PCR will be performed. Additionally, we will evaluate asymptomatic infections, by measuring SARS-CoV-2 serology every 4 weeks.

Detailed description: The SARS-CoV-2 infection has affected more than 100 countries around the world being classified as a pandemic by the World Health Organization. Health care providers are at high risk to become infected with the SARS-CoV-2 due to their continuous exposition to infected patients. Multiple strategies are being developed as potential prophylactic regimens, however to date (4th Aug 2020) none has proven to be effective for preventing the SARS-CoV-2 infection. Lactoferrin, an iron-binding protein with multiple physiological functions (anti-microbial, anti-inflammatory, and immunomodulatory), is one of the most important proteins present in mammalian milk. It has shown to inhibit the SARS entry to target cells by inhibiting the union of the SARS-CoV-2 spike protein with its receptor (ACE-II receptors), blocking the heparan sulfate proteoglycan receptor and it decreases the viral load of SARS-CoV-2 infecting culture cells in in vitro models. The study hypothesis is that lactoferrin given as a daily oral food supplement to health care workers will decrease the frequency of SARS-CoV-2 infection. The investigators will conduct a randomized double blinded placebo control clinical trial in physicians, nurses and nurse assistants who work in areas of care for patients with COVID-19 (emergency, hospitalization, and Intensive Care Unit) in hospitals in Lima, Peru, to determine the effect of bovine lactoferrin on the prevention of COVID-19 infection.

Eligibility criteria: Inclusion Criteria:

* Man or woman over 18 and under 60 years old
* Physicians or nurses or nurse assitant who work in areas of care for patients with COVID-19 (emergency, hospitalization, and Intensive Care Unit) in hospitals in Lima, Peru.
* Healthy participants, without COVID-19 suggestive symptoms
* Participant who wants to participate and signs the informed consent.

Exclusion Criteria:

* Participant who had a previous diagnosis of COVID-19.
* Participant positive in the initial screening for IgM or IgG or a positive RT-PCR for SARS-CoV-2.
* Participant with the following comorbidities: hypertension, coronary heart disease, diabetes mellitus, obesity, chronic lung disease, cancer, kidney failure, or other hematological disease.
* Pregnant woman.
* Participant that are part of another clinical trial or are taking any supplement or preventive treatment for COVID-19.
* Participant with known allergy to cow's milk protein.

Primary outcomes:
measure: Number of COVID-19 infections during the 12 weeks of intervention
timeFrame: Twelve weeks
Secondary outcomes:
measure: Severity of the COVID-19 infection
timeFrame: Twelve weeks
measure: Duration of symptoms of the COVID-19 infection
timeFrame: Twelve weeks
measure: Frecuency of symptoms of the COVID-19 infection
timeFrame: Twelve weeks
Other outcomes:
Locations:
city: Lima
country: Peru
facility: Hospital Nacional Arzobispo Loayza
state: Lim
city: Lima
country: Peru
facility: Hospital Cayetano Heredia
Study officials:
affiliation: Universidad Peruana Cayetano Heredia
name: Theresa J Ochoa, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Legrand D. Overview of Lactoferrin as a Natural Immune Modulator. J Pediatr. 2016 Jun;173 Suppl:S10-5. doi: 10.1016/j.jpeds.2016.02.071.
citation: Baker HM, Baker EN. A structural perspective on lactoferrin function. Biochem Cell Biol. 2012 Jun;90(3):320-8. doi: 10.1139/o11-071. Epub 2012 Jan 31.
citation: Chang R, Ng TB, Sun WZ. Lactoferrin as potential preventative and adjunct treatment for COVID-19. Int J Antimicrob Agents. 2020 Sep;56(3):106118. doi: 10.1016/j.ijantimicag.2020.106118. Epub 2020 Jul 30.
citation: Lang J, Yang N, Deng J, Liu K, Yang P, Zhang G, Jiang C. Inhibition of SARS pseudovirus cell entry by lactoferrin binding to heparan sulfate proteoglycans. PLoS One. 2011;6(8):e23710. doi: 10.1371/journal.pone.0023710. Epub 2011 Aug 22.
citation: Campione E, Cosio T, Rosa L, Lanna C, Di Girolamo S, Gaziano R, Valenti P, Bianchi L. Lactoferrin as Protective Natural Barrier of Respiratory and Intestinal Mucosa against Coronavirus Infection and Inflammation. Int J Mol Sci. 2020 Jul 11;21(14):4903. doi: 10.3390/ijms21144903.
citation: Mirabelli C, Wotring JW, Zhang CJ, McCarty SM, Fursmidt R, Frum T, Kadambi NS, Amin AT, O'Meara TR, Pretto CD, Spence JR, Huang J, Alysandratos KD, Kotton DN, Handelman SK, Wobus CE, Weatherwax KJ, Mashour GA, O'Meara MJ, Sexton JZ. Morphological Cell Profiling of SARS-CoV-2 Infection Identifies Drug Repurposing Candidates for COVID-19. bioRxiv [Preprint]. 2020 Dec 7:2020.05.27.117184. doi: 10.1101/2020.05.27.117184.
citation: Marques de Carvalho CA, da Rocha Matos A, Caetano BC, de Sousa Junior IP, da Costa Campos SP, Geraldino BR, et al. In Vitro Inhibition of SARS-CoV-2 Infection by Bovine Lactoferrin [Internet]. Microbiology; 2020 May [cited 2020 May 25]. Available from: http://biorxiv.org/lookup/doi/10.1101/2020.05.13.093781