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

COVID-19 Clinical Trial

— COVID-19_LF  

Official title:

Clinical Assessment of Oral Lactoferrin as a Safe Antiviral and Immunoregulatory Therapy in Patients Diagnosed With COVID-19 Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04412395
• Other study ID #: COVID-19_LF
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: February 1, 2022
• Est. completion date: December 30, 2022

Study information

• Verified date: November 2021
• Source: National Research Centre, Egypt
• Contact: Rehab Hegazy, PhD
• Phone: +201001507676
• Email: rehab_hegazy[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 516
• Est. completion date: December 30, 2022
• Est. primary completion date: August 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Communicable Diseases
• Corona Virus Infection
• Coronavirus Infection
• Coronavirus Infections
• COVID-19
• Infections
• Middle East Respiratory Syndrome (MERS)
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• SARS-CoV 2
• Syndrome

Intervention

Dietary Supplement:
• Lactoferrin (Apolactoferrin)
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.

Drug:
• Placebo of excipient(s) will be administered
Placebo of the equivalent excipient will be administered to placebo group

Locations

Country	Name	City	State
Egypt	Clinical Trial Unit National Research Center	Cairo
Egypt	Clinmax CRO (Clinical Research Organization)	Cairo
Egypt	Egyptian Military Medical Services (Hospitals)	Cairo
Egypt	National Research Center, Egypt (Clinical and Molecular Pharmacology)	Cairo	Giza

Sponsors (2)

Lead Sponsor	Collaborator
National Research Centre, Egypt	Egyptian Military Medical Services

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival rate.	Comparing the influence of the intervention on the Survival rate.	up to 8 weeks.
Primary	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.	up to 4 weeks.
Primary	The number of patients with PCR negative results.	Comparing the influence of the intervention on the PCR negative results.	up to 4 weeks.
Secondary	Mean change in the disease severity (clinical assessment).	Recording the changes from severe to moderate or mild and the time taken.	up to 4 weeks.
Secondary	Mean change in blood pressure.	Recording the changes in blood pressure mmHg.	up to 4 weeks.
Secondary	Mean change in heart beats.	Recording the changes in heart rate in beat/second.	up to 4 weeks.
Secondary	Mean change in body temperature.	Recording the changes in body temperature in Celsius.	up to 4 weeks.
Secondary	Mean change in body respiratory rate.	Recording the changes in the respiratory rate in breath/minute.	up to 4 weeks.
Secondary	Mean change in oxygen saturation.	Recording the changes in arterial oxygen saturation in mmHg.	up to 4 weeks.
Secondary	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).	up to 4 weeks.
Secondary	Mean change in complete blood picture (CBC).	Recording the changes in complete blood picture (CBC) in cells per liter.	up to 4 weeks.
Secondary	Mean change in C reactive protein (CRP).	Recording the changes in C reactive protein (CRP) in mg/L.	up to 4 weeks.
Secondary	Mean change in erythrocyte sedimentation rate (ESR).	Recording the changes in erythrocyte sedimentation rate (ESR) in mm/hr.	up to 4 weeks.
Secondary	Mean change in D-dimer.	Recording the changes in D-dimer in ng/mL.	up to 4 weeks.
Secondary	Mean change in ferritin.	Recording the changes in ferritin in ng/mL.	up to 4 weeks.
Secondary	Mean change in liver Albumin.	Recording the changes in liver Albumin in g/L.	up to 4 weeks.
Secondary	Mean change in total and direct Bilirubin.	Recording the changes in total and direct Bilirubin in mg/dL.	up to 4 weeks.
Secondary	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).	up to 4 weeks.
Secondary	Mean change in aspartate aminotransferase (AST).	Recording the changes in aspartate aminotransferase (AST) in IU/L.	up to 4 weeks.
Secondary	Mean change in Alanine Aminotransferase (ALT).	Recording the changes in Alanine Aminotransferase (ALT) in IU/L.	up to 4 weeks.
Secondary	Mean change in Blood Urea Nitrogen (BUN).	Recording the changes in Blood Urea Nitrogen (BUN) in mg/dL.	up to 4 weeks.
Secondary	Mean change in Serum Creatinine.	Recording the changes in Serum Creatinine in mg/dL.	up to 4 weeks.
Secondary	Mean change in Serum Creatinine clearance.	Recording the changes in Serum Creatinine in ml/min.	up to 4 weeks.
Secondary	Mean change in Glomerular filtration rate (GFR ).	Recording the changes in Glomerular filtration rate (GFR ) ml/min/m2.	up to 4 weeks.
Secondary	The mean change in serum interleukin-1 (IL-1).	Recording the changes in interleukin-1 (IL-1) in pg/ml.	up to 4 weeks.
Secondary	The mean change in serum interleukin-6 (IL-6).	Recording the changes in interleukin-6 (IL-6) in pg/ml.	up to 4 weeks.
Secondary	The mean change in serum interleukin-10 (IL-10).	Recording the changes in interleukin-10 (IL-10) in pg/ml.	up to 4 weeks.
Secondary	The mean change in serum tumor necrosis factor-alpha (TNF alpha).	Recording the changes in tumor necrosis factor-alpha (TNF alpha) in ng/ml.	up to 4 weeks.
Secondary	Mean changes in immunoglobulin G (IgG).	Recording the changes in immunoglobulin G (IgG) in ng/ml.	up to 4 weeks.
Secondary	Mean changes in immunoglobulin M (IgM).	Recording the changes in immunoglobulin M (IgM) in ng/ml.	up to 4 weeks.
Secondary	The mean change in PCR viral load.	Recording the changes in PCR viral load in copies/mL.	up to 4 weeks.
Secondary	Mean change in lung CT manifestation.	Recording the changes in lung CT.	up to 4 weeks.
Secondary	Nature and severity of Adverse Events.	Recording any unexpected Adverse Events of the intervention.	up to 4 weeks.
Secondary	Time for lung recovery.	Recording the changes (the average time of lung imaging recovery), as assessed by lung CT.	up to 8 weeks.
Secondary	The number of missed drug doses among each treatment group.	Recording the changes the event of missed drug doses.	up to 4 weeks.