Cannabidiol (CBD) in Patients With Mild to Moderate Symptoms of Coronavirus 2019: A Randomized, Double-blind, Placebo-controlled Clinical Trial
试验速览
- 阶段
- 2 期
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Prevention of severe/critical stage of Covid19
研究概览
简要总结
The aim of this work is to conduct a randomized, double-blind, placebo-controlled clinical trial to assess the efficacy and safety of cannabidiol (CBD - 300 mg a day) in patients infected with SARS-CoV-2.
The specific objectives are to assess whether, in patients with mild and moderate forms of SARS-CoV-2, daily use of CBD 300 mg for fourteen days is capable of:
i) decrease viral load; ii) modify inflammatory parameters, such as cytokines, measured from serum; iii) reduce clinical and emotional symptoms through daily clinical evaluation; iv) improve sleep; v) reduce hospitalization and worsen the severity of the disease; v) Monitor the possible adverse effects of CBD use in these patients.
详细描述
The present study will be a single-center, randomized, parallel, double-blind, placebo-controlled clinical trial of CBD in patients with mild to moderate SARS-CoV-2 infection. The investigators will use random stratification by minimizing the sample to stratify all eligible patients according to gender, age, disease severity (mild or moderate) and presence of comorbidity (controlled diabetes and/or hypertension), followed by random designation (in a ratio 1: 1) in each stratum to ensure a balanced distribution of disease severity among treatment groups (CBD plus symptomatic clinical and pharmacological measures) and control (symptomatic clinical and pharmacological measures and placebo). All patients will receive the clinical and pharmacological measures standardized by the Brazilian Ministry of Health's practical guidelines for diagnosis and treatment for mild and moderate cases for SARS-CoV-2 (https://portalarquivos.saude.gov.br/images/pdf /2020/April/18/Dirursos-Covid19.pdf). In other words, the following pharmacological measures: "prescription of drugs for symptom control, if there is no contraindication, with the possibility of intercalating antipyretic drugs in cases of difficult control of fever. • Oral antipyretic: 1st option: Paracetamol 500-1000 mg/dose (maximum 3mg / day) • 2nd option: Dipyrone 500-1000 mg VO (maximum dose in adults 4 grams)", and clinical measures:" Home isolation by 14 days from the date of onset of symptoms; review every 48 hours, preferably by phone, providing face-to-face assistance, if necessary; maintain rest, a balanced diet and a good supply of fluids; isolation from home contacts for 14 days".
Thus, all patients will receive clinical and pharmacological measures of symptoms. Patients in the investigational treatment group will also receive CBD within 24 hours after randomization, with a daily dose of 300mg / day (two 150mg doses; 1mL of the formulation) for 14 days. Patients in the placebo group will also receive, within 24 hours after randomization, 1mL of the same investigational medication vehicle (medium/coconut chain triglyceride oil - MCT) for 14 days, using a dosing device/syringe indistinguishable from the CBD medication. Patients, nursing staff, laboratory technicians, doctors who will carry out the assessments, researchers, and statisticians will be blind to the treatment group and will not know about the treatment information.
Secretions from the upper respiratory tract, lower respiratory tract, or both, by swab, will be obtained from each patient in the screening (day -3 to day 1) during treatment and post-treatment follow-up at the patient's home on days 1, 2, 3, 4, 5, 7, 10, 14, 21, and 28, to test the viral load and SARS-CoV-2 genotyping. On all these dates, nurses will visit home to collect swab (only from the oropharynx, to minimize discomfort), blood and will be evaluated at each visit for vital signs, pulse oximetry, odor test, and treatment guidelines. Each patient will also receive a digital thermometer to measure the axillary temperature in case of suspected fever and daily measurement immediately before lunch and dinner.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients of both sexes, older than 18 years of age, with SARS-CoV-2 infection confirmed in upper or lower respiratory tract secretion, through reverse transcription followed by polymerase chain reaction (RT- PCR), with mild or moderate manifestations of Covid-19, who wish to participate, and consent by signing the informed consent form and not involved in another clinical trial during the study period
- •Pneumonia assessed clinically and / or radiologically will not be mandatory for inclusion
- •Have a telephone (cellular or landline) that may be available to receive daily calls throughout the study period.
- •Willingness to voluntarily participate in the study to accept randomization for either treatment arm.
- •Signing of the approved Free and Informed Consent Form (ICF) by the Research Ethics Committee (CEP) and CONEP
排除标准
- •Age below 18 years
- •Patients who do not want or can fulfill the necessary home isolation for at least 14 days
- •Chronic clinical conditions, severe or not compensated, such as: insulin-dependent diabetes (types 1 or 2); uncontrolled hypertension, lung disease such as asthma or COPD; hematological and liver diseases, chronic kidney disease in advanced stage (grades 3, 4 and 5), metabolic disorders and immunosuppression
- •Use of any medication with potential interaction with CBD (such as chloroquine, clobazan, warfarin, or valproic acid) or history of undesirable reactions prior to the use of this cannabinoid
- •Inability to use oral medication
- •Pregnancy or lactation
- •History of alcohol or drug addiction
- •Smoking in the last three years
- •Marijuana use in the last three months
- •Inability to cooperate with researchers due to cognitive impairment or mental state
- •Patients with severe forms of SARS-CoV-2, (on screening, inclusion or initial visit)
研究组 & 干预措施
Cannabidiol (CBD)
50 cases in the CBD group plus pharmacological and clinical measures. Patients in the investigational treatment group will receive CBD within 24 hours after randomization, with a daily dose of 300mg / day (two 150mg doses; 1mL of the formulation) for 14 days.
干预措施: Cannabidiol (Drug)
Placebo (PLB)
50 in the placebo group plus pharmacological and clinical measures. Patients in the placebo group will also receive, within 24 hours after randomization, 1mL of the same investigational medication vehicle (medium / coconut chain triglyceride oil - MCT) for 14 days
干预措施: PLACEBO (Other)
结局指标
主要结局
Prevention of severe/critical stage of Covid19
时间窗: Up to 28 days
Deterioration in clinical status from mild/moderate to severe/critical over time during the study period
Time to CoVid19 symptoms relief and number of participants with negative Clinical CoVid19 symptoms as assessed by CTCAE v5.0
时间窗: Up to 28 days
Clinical CoVid19 symptoms Clinical improvement
次要结局
- Increment of odor detection sensitivity(Through study completion, over time during the study period (day 0-28)])
- Change in proinflammatory cytokine concentration(Up to 28 days)
- Describe the parenchymal lung damage induced by COVID-19 through a qualitative analysis with chest CT(14 days)
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0(Up to 28 days)
- Time to clinical improvement with CTCAE v5.0 CoVid19 symptoms to 0(Up to 28 days)
- Number of participants that need hospitalisation(Up to 28 days)
- 28-day mortality(Up to 28 days)
- Time to positive-to-negative saliva 2019-n-CoV RT-PCR conversion(Up to 28 days)
- Reduction in viral load(Up to 28 days)
- Brief measure for assessing generalized anxiety disorder and depression(Through study completion, over time during the study period (day 0-28)])
研究者
Jose Alexandre de Souza Crippa
Professor of Psychiatry, MD, PhD
University of Sao Paulo