Standardized Olive Leaf Capsules; as a Co-therapy in the Treatment of COVID-19 Patients

• ClinicalTrials.gov Identifier: NCT04873349
• Recruitment Status: Not yet recruiting
• First Posted: May 5, 2021
• Last Update Posted: May 7, 2021
• Sponsor: Shimaa M. Abdelgawad
• Information provided by (Responsible Party): Shimaa M. Abdelgawad, Fayoum University

Study Description

Brief Summary:

Starting from December 2019, novel coronavirus disease 2019 (COVID-19) pandemic has caused a tremendous economic loss and unprecedented health crisis across the globe. Discovering an effective and safe drug candidates for the treatment of COVID-19 and its associated symptoms became a global urgent demand especially due to limited data that have been released regarding the vaccine efficacy and safety in humans. Reviewing the recent research, Olive leaf was selected as a potential co-therapy supplement for the treatment and the improvement of clinical manifestations in COVID-19 patients. Olive leaves reported to be rich in phenolic compounds such as oleuropein, hydroxy tyrosol, verbascoside, apigenin-7-glucoside and luteolin-7-glucoside which has been reported as anti-SARS-CoV-2 metabolites in recent In silico, computational and in vitro studies. In addition, olive leaf extract was previously reported in several in vivo studies for its anti-inflammatory, analgesic, antipyretic, immunomodulatory and anti-thrombotic activities which is of a great benefit in the control of associated inflammatory cytokine storm and disseminated intravascular coagulation in COVID-19 patients.

A placebo-controlled, randomized clinical trial at Fayoum University Hospital in Egypt will be conducted. RT-PCR confirmed COVID-19 adults showing mild to moderate disease will be enrolled in the study. Patients presenting with multi-organ failure, ventilator support, and chronic diseases (except diabetes mellitus and hypertension) were excluded. Patients were randomly assigned in 1:1 ratio to receive standardized olive leaves capsules (containing 20-50% oleuropein) or placebo up-to 10 days along with standard care. The expected outcomes included symptom alleviation, viral clearance, improvement of analysis (CBC, CRP, LDH, ESR, Ferritin, D-dimer, creatinine, ALT and AST) and a 30-day mortality in intention-to-treat population.

Condition or disease	Intervention/treatment	Phase
Covid19; COVID-19 Respiratory Infection; Symptoms and Signs; COVID-19 Acute Bronchitis; Disseminated Intravascular Coagulation	Dietary Supplement: Nusapure standardized olive leaves capsule, 750 mg (50% oleuropein)	Phase 2

Detailed Description:

Objectives:

We will evaluate the efficacy of standardized olive leaf capsules as additive therapy to the standard therapeutic regimen (for a period 10 days) on clinical symptoms, viral clearance, improvement of analysis:

1. Complete blood count (CBC).
2. C-Reactive Protein (CRP)
3. Lactate dehydrogenase (LDH).
4. Erythrocyte Sedimentation rate (ESR).
5. Serum Ferritin
6. D-dimer
7. Serum creatinine.
8. Alanine Amino Transferase (ALT) and Aspartate Amino Transferase (AST).
9. Also, a 30-day mortality in patients with confirmed COVID-19, who are mild to moderately ill.

Trial design:

This is a single-center, randomized, double-blind, placebo-controlled clinical trial with a parallel-group design conducted at Fayoum university Hospital, Fayoum, Egypt.

Research Plan and Methodology 1-Complete patient history will be recorded (other diseases, current medications, age, sex, etc.) 2-Clinical investigation of patients by the physicians at Chest Department, Fayoum University Hospital including measurements such as Temperature and Oxygen saturation.

3-Patients will be tested for infection by PCR and all patients to be enrolled at the study should show positive PCR result.

4-The following analysis will be carried out for all the patients included in the study; CBC, CRP, LDH, ESR, Ferritin, D-dimer, creatinine, ALT and AST before treatment and for follow up every five days.

5- A computerized tomography (CT) scan could be performed on chest before and after treatment.

Participants:

All outpatients admitted to Chest Diseases Departments of Fayoum university Hospital, will be screened for the following criteria.

Inclusion criteria:

1. Adults.
2. Confirmed SARS-CoV-2 diagnosis (positive polymerase chain reaction by nasopharyngeal swab).
3. Mild to Moderate COVID-19 patients.
4. No history of the current use of olive leaf capsules supplement.

Exclusion criteria:

1. Severe and critical COVID-19 patients who need hospitalization.
2. Patients need ventilatory support or showing chronic obstructive pulmonary disease (COPD).
3. Patients showing any chronic disease (except hypertension and diabetes mellitus).
4. Patients who have multiorgan failure.

3. Use of alcohol, other investigational medicines, and illegal drugs (during the last 30 days).

Intervention and comparator:

A total of 60 patients randomized into two groups (30 in each group). The patients will be divided into 2 groups Intervention group: All patients receive the standard treatment regimen for COVID-19, according to the Egyptian Ministry of Health protocol, along with 2-3 capsules/day of standardized olive leaf containing 20-50% oleuropein (500-750 mg oleuropein daily) for a period of ten days.

Control group: The standard therapeutic regimen for COVID-19 along with placebo capsules daily for a period of ten days.

Main outcomes:

The main outcomes are the improvement of clinical symptoms, as well as oxygen saturation, viral clearance, improvement of analysis (CBC, CRP, LDH, ESR, Ferritin, D-dimer, creatinine, ALT and AST) within 10 days of randomization in patients with confirmed COVID-19, who are mild to moderately ill.

Randomization:

Included patients will be allocated to one of the study arms using block randomization in a 1:1 ratio (each block consists of 10 patients). This randomization method ensures a balanced allocation between the arms during the study. A web-based system will generate random numbers for the allocation sequence and concealment of participants. Each number relates to one of the study arms.

Ethical considerations All participants should Sign informed consent and show willingness to accept randomization to any assigned treatment arm.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: Assessment of the Clinical Effectiveness of Standardized Olive Leaf Capsules; as a Co-therapy in the Treatment of Non-hospitalized COVID-19 Patients; a Randomized Clinical Trial
• Estimated Study Start Date: May 10, 2021
• Estimated Primary Completion Date: July 30, 2021
• Estimated Study Completion Date: September 30, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Olive leaf capsules; Non-hospitalized COVID-19 patients who have positive PCR results and show mild to moderate clinical manifestations and symptoms (20-30 patients) will receive a 50% standardized olive leaf capsule 750 mg (700 mg oleuropein/day; the active principle in olive leaf) two times daily for a period of ten days alongside with the Egyptian protocol medications. All the active comparator participants should be adults, with no chronic diseases (except hypertension and diabetes), non addict or alcoholics.	Dietary Supplement: Nusapure standardized olive leaves capsule, 750 mg (50% oleuropein); two study groups; test group will receive Nusapure standardized olive leaves capsule, 750 mg (50% oleuropein) while placebo group will receive starch group
Placebo Comparator: Starch capsules; Non-hospitalized COVID-19 patients who have positive PCR results and show mild to moderate clinical manifestations and symptoms (20-30 patients) will receive a placebo starch capsules (750 mg) two times daily for a period of ten days alongside with the Egyptian protocol medications. All the placebo comparator participants should be adults, with no chronic diseases (except hypertension and diabetes), non addict or alcoholics.	Dietary Supplement: Nusapure standardized olive leaves capsule, 750 mg (50% oleuropein); two study groups; test group will receive Nusapure standardized olive leaves capsule, 750 mg (50% oleuropein) while placebo group will receive starch group

Outcome Measures

Primary Outcome Measures :

1. Improving the clinical symptoms in mild to moderate COVID -19 patients [ Time Frame: 5 days after treatment ]
   It is expected that the examined drug will alleviate symptoms such as fever, cough, sore throat and muscles ache
2. Viral clearance in mild to moderate COVID -19 patients [ Time Frame: 10 days after treatment ]
   It is expected that the examined drug will make the Polymerase chain reaction (PCR ) results for the test group negative within 10 days of treatment
3. improvement of analysis (CBC, CRP, LDH, ESR, Ferritin, D-dimer, creatinine, ALT and AST) [ Time Frame: 5-10 days after treatment ]
   It is expected that the treatment will improve the lab analysis for treatment group such as increase lymphocyte count in complete blood count (CBC), prevent elevation and/or decrease the following elevated values of: D-dimer, C-Reactive protein (CRP), Lactate dehydrogenase (LDH), Erythrocyte sedimentation rate (ESR), creatinine, Alanine Amino Transferase (ALT) and Aspartate Amino Transferase (AST).

Secondary Outcome Measures :

1. evaluate 30-day mortality rate in patients with confirmed COVID-19 moderately ill [ Time Frame: 30 days after treatment ]
   It is expected that the drug will reduce the conversion in cases from moderate to sever cases and so decrease the mortality rate

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Adults.
2. Confirmed SARS-CoV-2 diagnosis (positive polymerase chain reaction by nasopharyngeal swab).
3. Mild to Moderate COVID-19 patients.
4. No history of the current use of olive leaf capsules supplement.

Exclusion Criteria:

1. Severe and critical COVID-19 patients who need hospitalization.
2. Patients need ventilatory support or showing chronic obstructive pulmonary disease (COPD).
3. Patients showing any chronic disease (except hypertension and diabetes mellitus).
4. Patients who have multiorgan failure.

3. Use of alcohol, other investigational medicines, and illegal drugs (during the last 30 days).

Contacts and Locations

No Contacts or Locations Provided

More Information

• Responsible Party: Shimaa M. Abdelgawad, Assisting lecturer, Pharmacognosy Department, Faculty of Pharmacy, Fayoum University, Egypt, Fayoum University
• ClinicalTrials.gov Identifier: NCT04873349
• Other Study ID Numbers: EC 2121
• First Posted: May 5, 2021
• Last Update Posted: May 7, 2021
• Last Verified: May 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• 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.: Yes

Keywords provided by Shimaa M. Abdelgawad, Fayoum University:

COVID-19, Infection, Bronchitis, Coagulation, Symptoms

Additional relevant MeSH terms:

COVID-19; Respiratory Tract Infections; Bronchitis; Disseminated Intravascular Coagulation; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Blood Coagulation Disorders; Hematologic Diseases; Hemorrhagic Disorders; Thrombophilia; Oleuropein; Anti-Infective Agents; Antihypertensive Agents; Vasodilator Agents