Clinical trial NCT04731116: Cannabidiol Treatment for Severe and Critical Coronavirus (COVID-19) Pulmonary Infection
Official title: Cannabidiol Treatment for Severe and Critical COVID-19 Pulmonary Infection
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: COVID-19
Lead sponsor: Rabin Medical Center
Sponsor class: OTHER
First posted: 2021-01-29
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Serum C-reactive protein (CRP) level
timeFrame: Daily measurement during 14 days
measure: Serum ferritin level
timeFrame: Daily measurement during 14 days
measure: Serum Interferon gamma-induced protein 10 (IP10) level
timeFrame: Daily measurement during 14 days
measure: Serum IL-6 level
timeFrame: Daily measurement during 14 days
measure: Serum TNF-related apoptosis-inducing ligand (TRAIL)
timeFrame: Daily measurement during 14 days
Secondary outcomes:
measure: Study drug related adverse events
timeFrame: 14 days
measure: Patient adherence to the study protocol
timeFrame: 14 days
measure: Ratio of arterial oxygen partial pressure (PaO2) to fractional inspired oxygen (FiO2) ratio (PaO2/FiO2 ratio) for ventilated patients
timeFrame: 14 days
measure: Length of ventilation for ventilated patients
timeFrame: 28 days
measure: Length of stay in the ICU
timeFrame: 28 days
measure: Survival by day 28
timeFrame: 28 days
measure: Remission of respiratory symptoms
timeFrame: 28 days
measure: Documented infections up to discharge
timeFrame: 28 days
measure: Sequential organ failure assistance (SOFA) score
timeFrame: 28 days
Other outcomes:
Locations:
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
Study officials:
affiliation: Rabin Medical Center
name: Ilya Kagan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.