Cannabidiol Treatment for Severe and Critical Coronavirus (COVID-19) Pulmonary Infection

COVID-19 Clinical Trial

Official title:

Cannabidiol Treatment for Severe and Critical COVID-19 Pulmonary Infection

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04731116
• Other study ID #: 0245-20-RMC
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 10, 2021
• Est. completion date: April 30, 2022

Study information

• Verified date: January 2021
• Source: Rabin Medical Center
• Contact: Ilya Kagan, MD
• Phone: 972-50-4065483
• Email: Ilyak[@]clalit.org.il
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Current management of COVID-19 (coronavirus) is mainly supportive, and respiratory failure from acute respiratory distress syndrome (ARDS) is the leading cause of mortality. Cytokines and chemokines are thought to play an important role in immunity and immunopathology during virus infections. Patients with severe COVID-19 have higher serum levels of pro-inflammatory cytokines (TNF-α, IL-1 and IL-6) and chemokines (IL-8) compared to individuals with mild disease or healthy controls, similar to patients with severe acute respiratory syndrome (SARS).

Cannabidiol (CBD), a nonpsychotropic ingredient of Cannabis sativa, possesses potent anti-inflammatory and immunosuppressive properties. These effects are mediated by T cell attrition and by inhibition of pro-inflammatory cytokine release (tumor necrosis factor-a, Interferon gamma, IL-1b, IL-6, and IL-17) and stimulation of anti-inflammatory cytokine production (IL-4, IL-5, IL-10, and IL-13). In a number of phase 2 trials involving more than 100 patients, our group was able to show the safety and efficacy of CBD in the prevention and treatment of graft-versus-host disease.

Based on these data, we will test the cytokine profile, safety and efficacy of CBD treatment in patients with severe and critical COVID-19 infection.

Description:

Study objectives:

1. Describe the impact of CBD on the cytokine profile in patients with severe and critical COVID-19 infection.

2. Explore the safety and efficacy of CBD treatment in patients with severe and critical COVID-19 pulmonary Infection.

Methods:

This is a single center, prospective open label phase 1/2-study which will be conducted in a Corona isolation ward.

Investigational therapy:

Cannabidiol 5% dissolved in olive oil, will be given orally or through a nasogastric tube at a dose of 150 mg twice daily during 14 days or until discharge (the earliest). This dose is based on safety data generated from more than 100 transplanted patients. Treatment duration may be extended up to 28 days according to the physician discretion. In case of intolerance to the dose of 150 mg twice daily, the dose of CBD will be reduced to the maximal tolerated dose.

In the case of grade 4 side effects related to CBD or in the case of inability to provide the CBD during more the 3 days, the patient will be withdrawn from the study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: April 30, 2022
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Laboratory-confirmed novel COVID-19 infection as determined by polymerase chain reaction, or other commercial or public health assay in oropharyngeal specimen within 72 hours prior to hospitalization.

• Patients with severe disease defined as individuals with pneumonia and one or more of the following criteria:

1. Respiratory rate = 30/min.

2. Oxygen saturation at room air less than 93%.

• Patients with critical disease defined as individuals with respiratory failure requiring mechanical ventilation

• Age18 years and older

• Informed consent has to be obtained from all patients. The patient will sign the Informed Consent Form before entering the study.

• Some patients are expected to be unable to legally consent due to critical illness, and sedation. In case a legal guardian exists, approach for consent will be made.

Exclusion Criteria:

• Allergy to CBD

• Documented infection

• Pregnant and lactating women

• Predicted clinically that there is no hope of survival

• GI intolerance

Related Conditions & MeSH terms

• COVID-19
• Infection

Intervention

Drug:
• Cannabidiol
Oral Cannabidiol 150 mg twice daily during 14 days

Locations

Country	Name	City	State
Israel	Rabin Medical Center	Petach Tikva

Sponsors (1)

Lead Sponsor	Collaborator
Rabin Medical Center

Country where clinical trial is conducted

Israel, 

References & Publications (1)

Yeshurun M, Shpilberg O, Herscovici C, Shargian L, Dreyer J, Peck A, Israeli M, Levy-Assaraf M, Gruenewald T, Mechoulam R, Raanani P, Ram R. Cannabidiol for the Prevention of Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation: Results of a Phase II Study. Biol Blood Marrow Transplant. 2015 Oct;21(10):1770-5. doi: 10.1016/j.bbmt.2015.05.018. Epub 2015 May 30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum C-reactive protein (CRP) level	Units of measurement mg%	Daily measurement during 14 days
Primary	Serum ferritin level	Units of measurement mg%	Daily measurement during 14 days
Primary	Serum Interferon gamma-induced protein 10 (IP10) level	Units of measurement pg/ml	Daily measurement during 14 days
Primary	Serum IL-6 level	Units of measurement pg/ml	Daily measurement during 14 days
Primary	Serum TNF-related apoptosis-inducing ligand (TRAIL)	Units of measurement pg/ml	Daily measurement during 14 days
Secondary	Study drug related adverse events	Number of participants with grade 3-4 study drug-related side effects as assessed by Common Terminology Criteria for Adverse Event (CTCAE) version 5.0 during treatment.	14 days
Secondary	Patient adherence to the study protocol	Number of cannabidiol doses actually taken by the patient divided by 28 (number of planned doses)	14 days
Secondary	Ratio of arterial oxygen partial pressure (PaO2) to fractional inspired oxygen (FiO2) ratio (PaO2/FiO2 ratio) for ventilated patients	Daily measurement of ratio of arterial oxygen partial pressure (PaO2) to fractional inspired oxygen (FiO2) ratio (PaO2/FiO2 ratio) for ventilated patients	14 days
Secondary	Length of ventilation for ventilated patients	Number of days patient in need of mechanical ventilation	28 days
Secondary	Length of stay in the ICU	Number of days the patient stays in ICU	28 days
Secondary	Survival by day 28	Patient alive (yes/no) on day 28	28 days
Secondary	Remission of respiratory symptoms	Patient without dyspnea and saturation above 93% at room air.	28 days
Secondary	Documented infections up to discharge	Any documented infection in addition to COVID	28 days
Secondary	Sequential organ failure assistance (SOFA) score	Sequential organ failure assistance score calculation:range 0 to 24. A higher score is associated with higher risk of ICU mortality.	28 days