COVID-19Phase 1/2NCT04731116
Cannabidiol Treatment for Severe and Critical Coronavirus (COVID-19) Pulmonary Infection
A Phase 1/2 study testing Cannabidiol in people with COVID-19, run by Rabin Medical Center at 1 site in Israel.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19
- What is being tested?
- Cannabidiol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteIsrael
- Study dates
- 10 Jan 2021to 30 Apr 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- Respiratory rate ≥ 30/min.
- 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.
Who cannot join
- Allergy to CBD
- Documented infection
- Pregnant and lactating women
- Predicted clinically that there is no hope of survival
- GI intolerance
Trial locations and contacts
1 site in 1 country.
Israel1 site, 1 recruiting
- Recruiting
Rabin Medical Center
Petah Tikva
Ilya Kagan, MD, 972-50-4065483, Ilyak@clalit.org.il
Moshe Yeshurun, MD, moshey@clalit.org.il
About this study
Official title: Cannabidiol Treatment for Severe and Critical COVID-19 Pulmonary Infection
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.
Read the detailed description
Study objectives:
- Describe the impact of CBD on the cytokine profile in patients with severe and critical COVID-19 infection.
- 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.
- Conditions
- COVID-19
- Being tested
- Cannabidiol
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CannabidiolDrug
Oral Cannabidiol 150 mg twice daily during 14 days
| Study group | Role | What they receive |
|---|---|---|
| CANNABIDIOL | Experimental | CANNABIDIOL 5% 3 ml twice daily for 14 days. Receives: Drug: Cannabidiol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum C-reactive protein (CRP) level
Units of measurement mg%
Measured: Daily measurement during 14 days
Serum ferritin level
Units of measurement mg%
Measured: Daily measurement during 14 days
Serum Interferon gamma-induced protein 10 (IP10) level
Units of measurement pg/ml
Measured: Daily measurement during 14 days
Serum IL-6 level
Units of measurement pg/ml
Measured: Daily measurement during 14 days
Serum TNF-related apoptosis-inducing ligand (TRAIL)
Units of measurement pg/ml
Measured: Daily measurement during 14 days
Secondary outcomes (9)
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.
Measured: 14 days
Patient adherence to the study protocol
Number of cannabidiol doses actually taken by the patient divided by 28 (number of planned doses)
Measured: 14 days
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
Measured: 14 days
Length of ventilation for ventilated patients
Number of days patient in need of mechanical ventilation
Measured: 28 days
Length of stay in the ICU
Number of days the patient stays in ICU
Measured: 28 days
Survival by day 28
Patient alive (yes/no) on day 28
Measured: 28 days
Remission of respiratory symptoms
Patient without dyspnea and saturation above 93% at room air.
Measured: 28 days
Documented infections up to discharge
Any documented infection in addition to COVID
Measured: 28 days
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.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2021
- Study start10 Jan 2021
- Primary completion31 Dec 2021 (estimated)
- Study completion30 Apr 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rabin Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, moshe yeshurun, Rabin Medical Center
- Investigators
- Ilya Kagan, MD, Principal investigator, Rabin Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04731116
- Sponsor's protocol ID
- 0245-20-RMC
- Status last verified
- Jan 2021
- First submitted
- 28 Jan 2021
- Last updated
- 29 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 26033282
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cannabidiol Treatment for Severe and Critical COVID-19 Pulmonary Infection
- ClinicalTrials.gov ID
- NCT04731116
- Acronym / sponsor ID
- 0245-20-RMC
- Conditions
- COVID-19
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Rabin Medical CenterUniversity, hospital or other
- Study start
- 10 Jan 2021 (actual)
- Primary completion
- 31 Dec 2021 (estimated)
- Study completion
- 30 Apr 2022 (estimated)
- First posted
- 29 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Describe the impact of CBD on the cytokine profile in patients with severe and critical COVID-19 infection.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CANNABIDIOL | Experimental | Drug: CannabidiolCANNABIDIOL 5% 3 ml twice daily for 14 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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:
- 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.
Key exclusion criteria (5 listed)
- Allergy to CBD
- Documented infection
- Pregnant and lactating women
- Predicted clinically that there is no hope of survival
- GI intolerance
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CannabidiolOral Cannabidiol 150 mg twice daily during 14 days | Drug | CANNABIDIOL |
Primary outcome
Serum C-reactive protein (CRP) level
Time frame: Daily measurement during 14 days
Units of measurement mg%
Serum ferritin level
Time frame: Daily measurement during 14 days
Units of measurement mg%
Serum Interferon gamma-induced protein 10 (IP10) level
Time frame: Daily measurement during 14 days
Units of measurement pg/ml
Serum IL-6 level
Time frame: Daily measurement during 14 days
Units of measurement pg/ml
Serum TNF-related apoptosis-inducing ligand (TRAIL)
Time frame: Daily measurement during 14 days
Units of measurement pg/ml
9 secondary outcomes
Study drug related adverse events
Time frame: 14 days
Patient adherence to the study protocol
Time frame: 14 days
Ratio of arterial oxygen partial pressure (PaO2) to fractional inspired oxygen (FiO2) ratio (PaO2/FiO2 ratio) for ventilated patients
Time frame: 14 days
Length of ventilation for ventilated patients
Time frame: 28 days
Length of stay in the ICU
Time frame: 28 days
Survival by day 28
Time frame: 28 days
Remission of respiratory symptoms
Time frame: 28 days
Documented infections up to discharge
Time frame: 28 days
Sequential organ failure assistance (SOFA) score
Time frame: 28 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2021.
- Background: PubMed 26033282Yeshurun 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ilya Kagan, MD principal investigator
Rabin Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Cannabidiol in people with COVID-19, run by Rabin Medical Center at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ilya Kagan, MD (972-50-4065483, Ilyak@clalit.org.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum C-reactive protein (CRP) level (time frame: Daily measurement during 14 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04731116, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2021.