Clinical trial NCT06452069: Efficacy and Safety Study of Essential Oil-Based Preparation Administered to COVID-19 Patients
Official title: A Multicentre, Randomised, Prospective Study Investigating the Efficacy and Safety of an Essential Oil-Based Preparation Administered to Mild and Moderately Severe COVID-19 Positive Patients
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: COVID-19 Respiratory Infection
COVID-19
Keywords: Essential Oil, antiviral, Main Protease, COVID 19
Lead sponsor: Biodex S.A
Sponsor class: INDUSTRY
Collaborators: name: Gama CRO Tıbbi IIac Arastirma Org.Tic.Ltd.Sti
First posted: 2024-06-11
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter, Randomized, Prospective Study
Primary purpose: TREATMENT

Brief summary: The aim of this study was to compare the efficacy and safety of the essential oil-based product in patients with mild to moderate symptomatic COVID-19 Positive infection confirmed by PCR. A computational simulation approach of the molecular interaction (binding) of the main components of essential oils exhibiting antiviral activity with known intracellular protein targets of SARS-CoV-2 (nsp5: Main Protease) was adopted as a rationale for this study. SARS-CoV-2, a single-stranded RNA virus, has four major structural proteins Spike (S), Membrane (M), Envelope glycoprotein (E) and Nucleocapsid (N) protein and non-structural proteins (nsp). These non-structural proteins, of which there are 16 in total in the genome of the virus, play key roles in the mechanisms of the virus life cycle, including replication, transcription, protein synthesis and modification of RNA. Main protease (Main protease, Mpro, 3CLpro), virus Since they are directly involved in the maturation of these nsp proteins, which have an important role in many mechanisms of the life cycle, they have been the target enzyme in the development of new antiviral drugs for the treatment of COVID-19. In this study, our main rationale is to investigate the effect of essential oils on nsp5: Main Protease enzyme activations.

Detailed description: The indiscriminate use of antimicrobial agents has led to the emergence of a number of drug-resistant bacteria, fungi and viruses. To overcome the increasing resistance of pathogenic microbes, more effective antimicrobial agents with new modes of action must be developed.

Medicinal plants used in traditional medicines to treat infectious diseases are an abundant source of new bioactive secondary metabolites. Therefore, in the last few years, various medicinal plants and plant extracts have been screened for their antimicrobial activities . Essential oils obtained from aromatic medicinal plants (e.g. fennel (Foeniculum vulgare), mint (Mentha piperita), thyme (Thymus vulgaris)) have been shown to have antimicrobial activity against gram-positive and gram-negative bacteria as well as yeasts, It has been reported to be active against fungi and viruses. They are mixtures of different lipophilic and volatile substances such as monoterpenes, sesquiterpenes and/or phenylpropanoids and have a pleasant odour. They are also part of the pre-formed defence system of higher plants are thought to be . Monoterpenes have been widely studied, especially for their antiviral properties.

Nowadays, the use of essential oils is becoming increasingly widespread both in pharmacies and in various stores. The use of essential oils for therapeutic purposes is expanding. The molecules that make up certain essential oils have shown various antiviral properties:

* Either by neutralising the virus before it enters the cell,
* By changing the capsid or envelope of the virus,
* Either by binding to receptors used by viruses and preventing their access to cells.

Herbal products are an important source of herbal remedies and other medicines. Essential oils have shown various pharmacological activities, such as antiviral activity, and have therefore been implicated in SARS-CoV- It has been suggested to have potential activity against 2. Essential oils can easily penetrate the viral membrane due to their lipophilicity and can cause rupture of the viral membrane.

In addition, crude essential oils often have many active components that can act on different parts of the virus, including cell entry, translation, transcription and assembly. Anti-inflammatory, immune regulation on the respiratory system of the host, have other beneficial pharmacological effects, including bronchiectasis and mucolytics.

Essential oils have many advantages because they promise volatile antiviral molecules, making them useful either alone or in combination with other chemotherapeutic drugs, making them potential drug targets for the prevention and treatment of COVID-19.

In this study, a computational simulation approach of the molecular interaction (binding) of the main components of essential oils exhibiting antiviral activity with known intracellular protein targets of SARS-CoV-2 (nsp5: Master Protease) was adopted as a rationale. A single-chain.

The RNA virus SARS-CoV-2 has four main structural proteins Spike (S), Membrane (M), Envelope glycoprotein (E) and Nucleoapsid (N) proteins and non-structural proteins (nsp) .

These non-structural proteins, of which there are 16 in total in the genome of the virus, play a key role in the mechanisms of the virus life cycle, including replication, transcription, protein synthesis and modification of RNA. Main protease (Mpro, 3CLpro) has been the target enzyme for the development of new antiviral drugs for the treatment of COVID-19 , as they are directly involved in the maturation of these nsp proteins, which have an important role in many mechanisms of the virus life cycle. Our main rationale in this study is to investigate the effect of essential oils on nsp5: Main Protease enzyme activations.

Eligibility criteria: Inclusion Criteria:

* Patients must be between 18\<X\< 65 years of age.
* The participant must be willing and able to give written informed consent. The volunteer must provide his/her consent on his or her behalf, a legally acceptable representative (i.e., an International Harmonization Council \[ICH\] and adopted by local law as appropriate can be used) must give informed consent on his/her behalf.
* PCR test COVID-19 positive diagnosis and mild to moderate disease stage is required.
* The participant must agree not to receive vaccines administered for COVID-19 during the study.

Exclusion Criteria:

* Patients \< 18 years of age,
* Positive diagnosis of severe COVID-19 with symptoms of basic severity: patients with respiratory distress, signs of mental confusion and impaired consciousness that develop depending on the severity of the stage of the disease,
* Patients on active antiviral therapy,
* Patients with creatine clearance \< 30 ml/min and renal impairment,
* NYHA III-IV, Stage D heart failure patients requiring frequent hospitalization,
* Uncontrolled coagulopathy,
* Patients with advanced liver failure,
* Patients with active infections such as hepatitis B, hepatitis C and HIV, diseases requiring systemic treatment,
* Patients with active malignancy and known history of cancer,
* Those who do not have sufficient psychic state to disrupt working rounds,
* Active drug users,
* Known hypersensitivity and allergic reaction to the components of the preparation,
* Current participation in another interventional treatment study with an investigational agent,
* Recent use of the investigational product within 28 days of the first dose of the investigational product use or presence of a research device during screening,
* Pregnant or breastfeeding women,
* Patients who did not give written informed consent.

Primary outcomes:
measure: Clinical and virological cure rate in patients with PCR-confirmed mild to moderate symptomatic COVID-19 Positive infection treated with an essential oil-based product
timeFrame: 0th Day
measure: Clinical and virological cure rate in patients with PCR-confirmed mild to moderate symptomatic COVID-19 Positive infection treated with an essential oil-based product
timeFrame: 2nd Day
measure: Clinical and virological cure rate in patients with PCR-confirmed mild to moderate symptomatic COVID-19 Positive infection treated with an essential oil-based product
timeFrame: 6th Day
measure: Clinical and virological cure rate in patients with PCR-confirmed mild to moderate symptomatic COVID-19 Positive infection treated with an essential oil-based product
timeFrame: 10th Day
measure: TClinical and virological cure rate in patients with PCR-confirmed mild to moderate symptomatic COVID-19 Positive infection treated with an essential oil-based product.
timeFrame: 20th Day
measure: Clinical recovery defined by the absence of clinical signs of infection
timeFrame: 0th Day
measure: Clinical recovery defined by the absence of clinical signs of infection
timeFrame: 2nd Day
measure: Clinical recovery defined by the absence of clinical signs of infection
timeFrame: 6th Day
measure: Clinical recovery defined by the absence of clinical signs of infection
timeFrame: 10th Day
measure: Clinical recovery defined by the absence of clinical signs of infection
timeFrame: 20th Day
measure: Aggravation of the clinical picture
timeFrame: 0th Day
measure: Aggravation of the clinical picture
timeFrame: 2nd Day
measure: Aggravation of the clinical picture
timeFrame: 6th Day
measure: Aggravation of the clinical picture
timeFrame: 10th Day
measure: Aggravation of the clinical picture
timeFrame: 20th Day
measure: Virological evaluation
timeFrame: 0th Day
measure: Virological evaluation
timeFrame: 6th Day
measure: Virological evaluation
timeFrame: 10th Day
measure: Virological evaluation
timeFrame: 20th Day
Secondary outcomes:
measure: Evaluation of time from inclusion to recovery in days
timeFrame: 0th Day
measure: Evaluation of time from inclusion to recovery in days
timeFrame: 6th Day
measure: Evaluation of time from inclusion to recovery in days
timeFrame: 10th Day
measure: Evaluation of time from inclusion to recovery in days
timeFrame: 20th Day
measure: Incidence of adverse events and serious advers event
timeFrame: 0th Day
measure: Incidence of adverse events and serious advers event
timeFrame: 2nd Day
measure: Incidence of adverse events and serious advers event
timeFrame: 6th Day
measure: Incidence of adverse events and serious advers event
timeFrame: 10th Day
measure: Incidence of adverse events and serious advers event
timeFrame: 20th Day
Other outcomes:
Locations:
city: Istanbul
country: Turkey
facility: Bağcılar Training and Research Hospital
state: Bagcılar
city: Istanbul
country: Turkey
facility: Gaziosmanpaşa Training and Research Hospital
state: Gaziosmanpaşa
city: Kocaeli
country: Turkey
facility: Kocaeli City Hospital
state: İzmit
city: Istanbul
country: Turkey
facility: Göztepe Süleyman Yalçın City Hospital
state: Kadıköy
city: Istanbul
country: Turkey
facility: Kartal Dr. Lütfi Kırdar City Hospital
state: Kartal
city: Antalya
country: Turkey
facility: Akdeniz University
state: Konyaaltı
city: Istanbul
country: Turkey
facility: Süreyyapaşa Chest Disease and Thoracic Surgery Training and Research Hospital
state: Maltepe
city: Istanbul
country: Turkey
facility: Umraniye Training and Research Hospital
state: Umraniye
city: Antalya
country: Turkey
facility: Antalya Atatürk Public Hospital
city: Istanbul
country: Turkey
facility: Cemil Taşcıoğlu City Hospital
state: Şişli
Study officials:
affiliation: Bagcilar Training and Research Hospital
name: Kanat Tayfun, MD
role: PRINCIPAL_INVESTIGATOR
References: