Clinical Assessment of Oral Lactoferrin as a Safe Antiviral and Immunoregulatory in Treating COVID-19 Disease

National Research Centre, Egypt516 enrolled

Overview

The aim of the study is to clinically use bovine Lf as a safe antiviral adjuvant for treatment and to assess the potential in reducing mortality and morbidity rates in COVID-19 patients. The study was approved by the ethical committee of the Egyptian Center for Research and Regenerative Medicine in 11-5-2020.

The World Health Organization (WHO) declared the coronavirus (SARS-CoV-2, COVID-19) outbreak a Public Health Emergency of International Concern with a pandemic spread. The situation is rapidly evolving, which raises the approach of reproposing already approved drugs to meet the emerging challenge and to save time and money. Lactoferrin (Lf) is a natural glycoprotein that broadly distributed within the body fluids and found predominantly in milk. It represents a known component of the innate immune system. The antiviral activity of Lf has been reported against many viruses, including SARS-CoV-1, through blocking the viral receptors on the host cells preventing them from entry and replication. Markedly, data reveals that Lf interacts with Heparan Sulfate Proteoglycans (HSPGs) and Angiotensin Converting Enzyme 2 (ACE2) receptors that are reported as SARS-CoV-2-binding sites to enter the host cell, suggesting a potential significance of Lf as an antiviral against SARS-CoV-2. Moreover, the immunoregulatory effects of Lf can protect against the cytokine-storm and thrombotic complications that result from the COVID-19-induced over-stimulated inflammatory response and exaggerated immune reactions. In addition, Lf can decrease the free iron toxicity caused by the virus as it has a strong iron chelating ability. Lf is a safe approved food supplement that is available in the markets for enhancement of immunity and for treatment of anemia. The aim of this study is to perform a randomized, double-blind, placebo-controlled, two arms, clinical trial to assess oral enteric-coated tablet of bovine apolactoferrin (the low iron-content form of Lf) as a safe antiviral and immunoregulatory therapy in patients diagnosed with COVID-19 disease.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

Interventions

Lactoferrin (Apolactoferrin)DIETARY_SUPPLEMENT

Apolactoferrin is an iron-free Lactoferrin (with very low iron saturation). Lactoferrin (Lf) is a natural glycoprotein that is found predominantly in milk. Lf represents a known component of the innate immune system present in neutrophil-specific granules and broadly distributed within the body fluids and exocrine secretions.

Placebo of excipient(s) will be administeredDRUG

Placebo of the equivalent excipient will be administered to placebo group

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients tested positive (PCR) for SARS-CoV-2 and clinically symptomatic. * Adult patients with age \>18 years. * Patients willing and able to sign the study informed consent form. Exclusion Criteria: * Critically severe disease patients (having Respiratory failure requiring mechanical ventilation, or signs of septic shock or multiple organ failure requiring ICU admission). * Patients who are unconscious * Patients who have convulsions * Patients suffering from central cyanosis with SPO2\< 90% (for asthmatic patients with SPO2\<88%) * Pregnant or lactating women * Patients with a known history of pro-inflammatory diseases (patients with autoimmune diseases, patients receiving chemotherapy for cancer, patients with malabsorption, patients with inflammatory bowel disease, Crohn's disease or ulcerative colitis). * History or suspected immunosuppressive or immunodeficient state including HIV infection, or chronic immunosuppressant medication (more than 14 days) within the past 3 months (inhaled and topical steroids are allowed). * Patients with severe renal impairment (GFR \<60 ml/min/1.73m2 as measured by the Cockcroft-Gault formula). * Patient with severe hepatic impairment, biliary cirrhosis or cholestasis * Patients who received immunoregulatory therapy within one month before the start of the study. * Patients with Known or suspected allergy or any contraindications to Lactoferrin. * Any condition, according to the judgment of the investigator, would interfere with the patient's ability to comply with all study requirements or that would place the patient at unacceptable risk by his/her participation in the study.

Locations (4)

National Research Center, Egypt (Clinical and Molecular Pharmacology)

Cairo, Giza Governorate, Egypt

Clinmax CRO (Clinical Research Organization)

Cairo, Egypt

Clinical Trial Unit National Research Center

Cairo, Egypt

Egyptian Military Medical Services (Hospitals)

Cairo, Egypt

Outcomes

Primary Outcomes

Survival rate.

Comparing the influence of the intervention on the Survival rate.

Time frame: up to 8 weeks.

Rate of disease remission.

For mild/moderate symptoms patients: fever, cough and other symptoms relieved with improved lung CT \- For severe symptoms patients: fever, cough and other symptoms relieved with improved lung CT, and oxygen saturation by pulse oximetry (SPO2 )\> 93% for nonasthmatic patients, and from 88-92% in asthmatic patients.

Time frame: up to 4 weeks.

The number of patients with PCR negative results.

Comparing the influence of the intervention on the PCR negative results.

Time frame: up to 4 weeks.

Secondary Outcomes

Mean change in the disease severity (clinical assessment).

Recording the changes from severe to moderate or mild and the time taken.

Time frame: up to 4 weeks.

Mean change in blood pressure.

Recording the changes in blood pressure mmHg.

Time frame: up to 4 weeks.

Mean change in heart beats.

Recording the changes in heart rate in beat/second.

Time frame: up to 4 weeks.

Mean change in body temperature.

Recording the changes in body temperature in Celsius.

Time frame: up to 4 weeks.

Mean change in body respiratory rate.

Recording the changes in the respiratory rate in breath/minute.

Time frame: up to 4 weeks.

Mean change in oxygen saturation.

Recording the changes in arterial oxygen saturation in mmHg.

Time frame: up to 4 weeks.

Mean change in the ratio in arterial oxygen partial pressure to fractional inspired oxygen (PF ratio).

Recording the changes in the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PF ratio).

Time frame: up to 4 weeks.

Mean change in complete blood picture (CBC).

Recording the changes in complete blood picture (CBC) in cells per liter.

Time frame: up to 4 weeks.

Mean change in C reactive protein (CRP).

Recording the changes in C reactive protein (CRP) in mg/L.

Time frame: up to 4 weeks.

Mean change in erythrocyte sedimentation rate (ESR).

Recording the changes in erythrocyte sedimentation rate (ESR) in mm/hr.

Time frame: up to 4 weeks.

Mean change in D-dimer.

Recording the changes in D-dimer in ng/mL.

Time frame: up to 4 weeks.

Mean change in ferritin.

Recording the changes in ferritin in ng/mL.

Time frame: up to 4 weeks.

Mean change in liver Albumin.

Recording the changes in liver Albumin in g/L.

Time frame: up to 4 weeks.

Mean change in total and direct Bilirubin.

Recording the changes in total and direct Bilirubin in mg/dL.

Time frame: up to 4 weeks.

Mean change in prothrombin time (PT) and partial thromboplastin time (PTT ).

Recording the changes in prothrombin time (PT), partial thromboplastin time (PTT ) in seconds and calculating International Normalized Ratio (INR).

Time frame: up to 4 weeks.

Mean change in aspartate aminotransferase (AST).

Recording the changes in aspartate aminotransferase (AST) in IU/L.

Time frame: up to 4 weeks.

Mean change in Alanine Aminotransferase (ALT).

Recording the changes in Alanine Aminotransferase (ALT) in IU/L.

Time frame: up to 4 weeks.

Mean change in Blood Urea Nitrogen (BUN).

Recording the changes in Blood Urea Nitrogen (BUN) in mg/dL.

Time frame: up to 4 weeks.

Mean change in Serum Creatinine.

Recording the changes in Serum Creatinine in mg/dL.

Time frame: up to 4 weeks.

Mean change in Serum Creatinine clearance.

Recording the changes in Serum Creatinine in ml/min.

Time frame: up to 4 weeks.

Mean change in Glomerular filtration rate (GFR ).

Recording the changes in Glomerular filtration rate (GFR ) ml/min/m2.

Time frame: up to 4 weeks.

The mean change in serum interleukin-1 (IL-1).

Recording the changes in interleukin-1 (IL-1) in pg/ml.

Time frame: up to 4 weeks.

The mean change in serum interleukin-6 (IL-6).

Recording the changes in interleukin-6 (IL-6) in pg/ml.

Time frame: up to 4 weeks.

The mean change in serum interleukin-10 (IL-10).

Recording the changes in interleukin-10 (IL-10) in pg/ml.

Time frame: up to 4 weeks.

The mean change in serum tumor necrosis factor-alpha (TNF alpha).

Recording the changes in tumor necrosis factor-alpha (TNF alpha) in ng/ml.

Time frame: up to 4 weeks.

Mean changes in immunoglobulin G (IgG).

Recording the changes in immunoglobulin G (IgG) in ng/ml.

Time frame: up to 4 weeks.

Mean changes in immunoglobulin M (IgM).

Recording the changes in immunoglobulin M (IgM) in ng/ml.

Time frame: up to 4 weeks.

The mean change in PCR viral load.

Recording the changes in PCR viral load in copies/mL.

Time frame: up to 4 weeks.

Mean change in lung CT manifestation.

Recording the changes in lung CT.

Time frame: up to 4 weeks.

Nature and severity of Adverse Events.

Recording any unexpected Adverse Events of the intervention.

Time frame: up to 4 weeks.

Time for lung recovery.

Recording the changes (the average time of lung imaging recovery), as assessed by lung CT.

Time frame: up to 8 weeks.

The number of missed drug doses among each treatment group.

Recording the changes the event of missed drug doses.

Time frame: up to 4 weeks.

Clinical Assessment of Oral Lactoferrin as a Safe Antiviral and Immunoregulatory in Treating COVID-19 Disease

Overview

Conditions

Interventions

Eligibility

Locations (4)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts