Efficacy and Safety of Ozonised Oil (HOO) in COVID-19 Patients (HOO-COVID)

• ClinicalTrials.gov Identifier: NCT04651387
• Recruitment Status: Withdrawn
• First Posted: December 3, 2020
• Last Update Posted: January 26, 2022
• Sponsor: Neuromed IRCCS
• Information provided by (Responsible Party): Licia Iacoviello, Neuromed IRCCS

Study Description

Brief Summary:

The anti-viral efficacy of ozone against RNA viruses is already established. Ozone gas have been already proposed as possible therapy for Covid-19 infection with insofar limited success. The development of ozonized oil (HOO) solved this problems making ozone highly stable and bioavailable due to its bound with the lipid carrier. HOO administration is totally noninvasive occurring by oral administration of pills or as nasal spray.

HOO regimen could be proposed as complimentary therapeutic treatment for Covid-19 infection, without the need of any modifications of the established standard therapeutic protocols. This complimentary treatment, could be helpful to (a) decrease the severity of the diseases lowering the number of Covid-19 patients requiring high-intensity therapies; (b) fasten qPCR negativization after disease and time-span of hospital recovery.

The objective of this study is to investigates the effectiveness of combined use of "HOO capsules" and "HOO oropharyngeal and nasal spray" as a therapeutic supplement in the treatment of patients with confirmed COVID-19, who are moderately ill.

Condition or disease	Intervention/treatment	Phase
SARS-CoV Infection	Dietary Supplement: Ozonized oil (HOO	Not Applicable

Detailed Description:

The anti-viral efficacy of ozone against RNA viruses is already established. Ozone gas have been already proposed as possible therapy for Covid-19 infection with insofar limited success. Indeed, in this form, ozone is extremely volatile and its beneficial effects are only transient. Furthermore, in these studies ozone was administered by auto-hemo-transfusion, an invasive approach that cannot be pursued for preventive purposes in healthy subjects or in severely affected patients. The development of ozonized oil (HOO) solved this problems making ozone highly stable and bioavailable due to its bound with the lipid carrier. HOO administration is totally noninvasive occurring by oral administration of pills or as nasal spray.

A challenge test was developed to identify new strategies to prevent Covid-19 infection. Sensitive cells expressing the ACE2 receptor were challenged with oro-pharyngeal containing high viral loads of Covid-19 and the amount of viral RNA able to penetrate inside the cells quantified by qPCR. The ability to inhibit viral infection by UV radiation, hydrogen peroxide, anti-spike Covid-19 antibodies and HOO was comparatively evaluated. The only agent able to fully neutralize Covid-19 was HOO.

The HOO efficacy in preventing finding is due to (a) the high sensitivity of Covid-19 to oxidative stress; (b) the high lipophilicity of Covid-19 and the wide exposure of its lipid envelope for the interaction with lipohilic HOO; (c) the sensitivity of Covid-19 spike proteins to oxidative stress induced by HOO due to their high abundancy of neutrophilic sulphur-rich sites; (d) the HOO capacity to penetrate inside the cells arresting Covid-19 intra-cellular assembly; (e) HOO anti-inflammatory properties causing inhibition of pulmonary macrophage activation, thromboxane release and consequent pulmonary thrombo-embolism, a severe complication occurring in Covid-19 patients; (f) the increased oxygen availability in lung parenchyma.

HOO regimen could be proposed as complimentary therapeutic treatment for Covid-19 infection, without the need of any modifications of the established standard therapeutic protocols. This complimentary treatment, could be helpful to (a) decrease the severity of the diseases lowering the number of Covid-19 patients requiring high-intensity therapies; (b) fasten qPCR negativization after disease and time-span of hospital recovery.

The objective of this study is to investigates the effectiveness of combined use of "HOO capsules" and "HOO oropharyngeal and nasal spray" as a therapeutic supplement in the treatment of patients with confirmed COVID-19, who are moderately ill.

This study is conducted as an open-label, prospective, controlled, multi-center randomized clinical trial on 74 COVID-19 patients (both sex , aged 18-80 years).

In addition to the routine standard treatments for COVID-19, in the intervention group, combined use of "HOO capsules" and "HOO oropharyngeal and nasal spray" will be administered 3 times per day and will be prescribed for 2 weeks (14 days). For the control group, the placebo will be not considered and they will follow the routine standard treatments for COVID-19.

The study is aimed at defining if HOO therapy decreases the viral load of SARS-CoV-2 (main outcome). Additionally, secondary objectives will be the assessment of the temporal profile of viral load, the proportion of patients with virological clearance, the hospitalization duration stay, intensive care admission and time to, the COVID-19 Severity and in-hospital mortality.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Efficacy and Safety of Ozonised Oil (HOO) as Adjuvant Nutrition Supplement in COVID-19 Patients With Mild-to-Moderate Disease - HOO-COVID Project
• Estimated Study Start Date: July 2021
• Estimated Primary Completion Date: December 2021
• Estimated Study Completion Date: December 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intervention group; In addition to the routine standard treatments for COVID-19, in the intervention group, combined use of "HOO capsules" and "HOO oropharyngeal and nasal spray" will be administered	Dietary Supplement: Ozonized oil (HOO; In addition to the routine standard treatments for COVID-19, in the intervention group, combined use of "HOO capsules" and "HOO oropharyngeal and nasal spray" will be administered 3 times per day (after breakfast, lunch, dinner, possibly with a delay of one hour from the routine treatment) and will be prescribed for 2 weeks (14 days). Posology: 3 HOO capsules plus 3 HOO intranasal administrations for each naris plus 3 HOO oropharyngeal administrations.
No Intervention: Control group; For the control group, the placebo will be not considered and they will follow the routine standard treatments for COVID-19.

Outcome Measures

Primary Outcome Measures :

1. Viral load of SARS-CoV-2 [ Time Frame: up to one week ]
   The study is aimed at defining if HOO therapy decreases the viral load of SARS-CoV-2 at day 7.

Secondary Outcome Measures :

1. The temporal profile of viral load of SARS-CoV-2 [ Time Frame: up to four weeks ]
   The temporal profile of viral load at baseline, day 7, 14 and 28
2. The proportion of patients with virological clearance [ Time Frame: up to four weeks ]
   The proportion of patients with virological clearance at day 14 and 28
3. SaO2 [ Time Frame: up to four weeks ]
   Increasing SaO2, day 7, 14 and 28
4. hospitalization stay [ Time Frame: through study completion, an average of 3 months ]
   The hospitalization duration stay
5. Intensive care [ Time Frame: through study completion, an average of 3 months ]
   Intensive care admission and time to
6. COVID-19 Severity Score [ Time Frame: up to four weeks ]
   The COVID-19 Severity Score at day 14 and 28 Score definition: 1 is "no limitation of activities"; 2 is "limitation of activities"; 3 is "hospitalized, no oxygen therapy"; 4 is " hospitalized, oxygen by mask or nasal prongs"; 5 is "non-invasive ventilation or high-flow oxygen"; 6 is "intubation and mechanical ventilation"; 7 is "ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)", and 8 is "death".
7. in-hospital mortality [ Time Frame: through study completion, an average of 3 months ]
   Death occurred during hospitalization.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Real time PCR-approved positive COVID-19 test (nasopharyngeal swabs).
• Both gender
• Age between 18 and 80 years
• Lack of participation in other clinical trials
• COVID-19 Severity Score ≤ 5
• Hospitalized ≤48 hours.
• Signing informed consent and willingness of the participant to accept randomization to any assigned treatment

Exclusion Criteria:

• Pregnancy and breastfeeding.
• BMI ≥35 kg/m2
• Severe and critical COVID-19 pneumonia (COVID-19 Severity Score > 5)
• Patient connected to the ventilator
• SaO2 less than 80%
• Having liver failure, chronic hepatitis, cirrhosis, and cholestatic liver diseases
• Any severe medical condition with a prognosis of < 6 months
• Alcohol and drug abuse (during the last 30 days)
• History of known allergy to peanuts

Contacts and Locations

Sponsors and Collaborators

Neuromed IRCCS

Investigators

• Principal Investigator: Licia Iacoviello, MD, PhD; IRCCS Neuromed

More Information

• Responsible Party: Licia Iacoviello, Professor, Neuromed IRCCS
• ClinicalTrials.gov Identifier: NCT04651387
• Other Study ID Numbers: DEP_052020
• First Posted: December 3, 2020
• Last Update Posted: January 26, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Licia Iacoviello, Neuromed IRCCS:

ozone therapy, decrease of viral load of SARS-CoV-2

Additional relevant MeSH terms:

Severe Acute Respiratory Syndrome; Respiratory Tract Infections; Infections; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases