Coronavirus disease (COVID-19), caused by the novel severe acute respiratory syndromecoronavirus 2 (SARS-CoV-2), presents a major threat to human health. SARS-CoV-2 is highlyinfectious and is associated with extensive morbidity and mortality. Our study sharesimportant features with other clinical trials using supplements or other widely availablemedications (e.g., Ascorbic Acid, Zinc, Vitamin D, Vitamin C). Our study shares twoimportant elements with these previous studies, including: 1. The use of adaptive and cost-effective study design methods, 2. The testing of prophylactic supplementation using known, natural substances that have demonstrated safety and limited side effects.The focus of this study is to use a supplement that combines Cannabidiol and GigartinaRed Algae in creating "CBDRA60", a sublingual tablet, which is hypothesized to helpreduce the duration of symptoms in patients diagnosed with the novel coronavirus disease(COVID-19). The rationale and design of our trial (N=60), is as follows: 60 individualsnewly diagnosed with COVID-19 infection will be randomized to one of two groups. Theywill either receive CBDRA60 (30mg CBD, 30mgRA / 60mg combo; 2x/daily with food or 120 mgtotal) or a placebo in a 1:1 ratio. The study duration will be 5 weeks. The primaryoutcome for newly diagnosed individuals is the prevention of disease progression whichleads to hospitalization. The secondary outcome is a reduction in symptom severityscores.COVID-19 patients with weakened innate immune systems may be susceptible to more severedisease and higher mortality. An impaired host immune response may lead to higherSARS-COV-2 viral load and subsequent overactivation of the adaptive immune system thatresults in cytokine release syndrome. CBD and Gigartina Red Algae can modulate both theinnate and adaptive immune responses, have anti-viral activity and thereby can suppressthe consequent hyperinflammatory response.Viral infection activates a pathological inflammatory response to combat the pathogen andlimit its spread. Viral pathogens, such as the severe acute respiratory syndrome (SARS)coronaviruses (SARS-CoV), and other viruses (such as HIV), have been linked to many humanand animal diseases. Advancements in research over the past decade, has led to a betterunderstanding of SARS-CoV biology and the mechanism by which this family of viruses, thecoronaviridae, infect and enter the host cells (refs). SARS-CoV-2, a unique type ofcoronavirus, inhibits host defense by invading host cells, replicating, and infectingnumerous tissues. Severe COVID-19 is associated with a cytokine storm, acute respiratorydistress and consequent multiple organ pathology that can be fatal. This depictive stormis a result of increase in circulating levels of various proinflammatory cytokinesincluding IL-6, IL-1 TNF-α as well as interferons (IFN-I; IFNα and IFNβ).CBD CBD is a non-psychotropic cannabinoid that has a broad spectrum of well-establishedanti-inflammatory and immunomodulatory effects. For example, CBD administration in amurine model of lung injury, reduces lung inflammation through inhibition of immune cellcytokine production and suppression of leukocyte infiltration. Our premise is thatsimilar CBD-induced effects would be highly applicable and hugely beneficial tomitigating the acute respiratory distress syndrome observed in COVID-19. Publishedevidence also indicates that CBD can inhibit viral replication. Red algae (Rhodophyta)are known for their potent anti-viral properties, non-toxicity and for being welltolerated in humans. Rhodophyta contain several sulfated polysaccharides that exhibithigh antiviral activity against enveloped viruses, including important human pathogenssuch as herpes simplex virus (HSV), human cytomegalovirus, dengue virus and respiratorysyncytial virus. Sulfated polysaccharides can exert their anti-viral effects throughinteracting with the external glycoprotein of the virion envelope preventing attachmentof the virus to cell surface receptors. Red algae also contain mannose specific lectinsthat specifically interact with viral envelope glycoproteins including the spikeglycoprotein specific to SARS-CoV2 to inhibit viral entry.It is our premise that by using a safe and tolerable dose of the formulated CBDRA60sublingual tablet, participants could either be protected from viral infection of theSARS-CoV-2 virus (COVID-19) or in subjects that are already infected, CBDRA60, couldprevent virus attachment, mitigate virus-induced inflammation and avoid a cytokine storm,enabling a faster recovery.
The trial is a randomized, double blind, placebo-controlled trial with a total of 60
participants located in the state of Michigan. Patients will be randomized to CBDRA60
supplement or placebo.
All participants will be newly diagnosed as positive for SARS-CoV2 (assessed using a PCR
test).
Each participant will be randomized to either CBDRA60 or placebo in a 1:1 ratio. The
study duration for each participant will be 5 weeks, including taking the supplementation
(active or placebo for 28 days). Of the 60 participants, 30 participants will receive
CBDRA60 and 30 participants will receive the placebo. The infected individuals will be
followed to assess disease progression defined as the need for hospitalization.
For participants receiving the CBDRA60 supplementation, it aims to reduce
1. The need to be hospitalized and
2. Self-reported disease severity and resolution over 5 weeks Participants will
self-report symptom severity and disease progression through weekly questionnaires.
For each specified COVID-19 related symptom (fever, cough, shortness of breath or
difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or
smell, sore throat, congestion or runny nose, nausea or vomiting, diarrhea),
participants will report one of the following 3 options: none (score of 0), mild
(score of 1), moderate (score of 2) or severe (score of 3) except for new loss of
taste or smell which will be assessed using a binary score (0 = no loss of
taste/smell, 1 = loss of taste/smell) in accordance with the HHS guidelines (Sep
2020 document). The total disease severity score will be the average across all
potential symptoms. The escalation protocol for any participants that experience
symptoms that are more than mild or continue to progress will be directed to contact
their primary care physician or their appropriate emergency care facility.
Supplementation Daily sublingual tablet containing 30mg Cannabidiol and 30mg Red Algae, a
total of 60mg per dose. Participants will take 2 tablets per day, sublingually and with
food, taken approximately and at least, 8 hours apart, daily for 28 days. Participants
will be mailed a supply of pills by an overnight courier service.
Control subjects will receive daily oral placebo tablets of identical appearance and
taste containing no CBDRA60.
Study procedures Recruitment Participants will be recruited across Michigan via social
media; community advocacy groups and equity initiatives; flyers and electronic
communications distributed in healthcare centers, COVID-19 testing centers, and other
avenues. Recruitment will primarily be conducted remotely and prospective participants
will be asked to complete a web-based HIPAA-secure screening survey by the MB Clinical or
VSafe system. Screen-eligible participants will be contacted by phone by research staff
to complete the screening process using on-line consent forms.
Baseline and follow-up Participants will receive messages as a reminder to take study
pills. They will also be instructed to complete 1x per week online questionnaires for 5
weeks and an additional post study follow-up questionnaire at week 8. The questionnaire
will include items on adherence with randomized supplementation with CBDRA60/placebo, use
of non-trial supplements of CBD, development of symptoms and new illness, and self-report
of disease progression and severity status. Non-responders to online notification will be
telephoned to collect study data.
Data Management Using ClinOne or VSafe Platform
ClinOne, a clinical research organization (CRO) with a Vsafe platform will be implemented
for key areas of improvement of patient engagement and retention throughout the
investigation. It provides remote online services between patients and the clinicians in
charge. It further provides services for:
- Required screening criteria,
- Questionnaires,
- Study contact,
- Recorded investigatory meetings,
- CEO and KOL presentation and important messages,
- Training videos. All through a secure online platform.
All the services can be accessed via the ClinOne or VSafe platform. Patients will use the
platform for reminders, to access study information, report questions or concerns, and
communicate with principal investigators and physician. The platform allows the clinical
trial leader to schedule events via its manager system (S.O.E.M). It is a secure portal
to share approved study documents, provide a concierge and knowledge digital base,
research visits, and ePro lite which will be used to deliver the questionnaires to
patients and guarantee the collection of evaluable data. For reminders on when to take
the CBDRA 60 sublingual tablet an electronic eDosing adherence reminder will be available
to notify the study participants.
Lastly, in order to monitor the subjects health, remotely, and to collect additional
biometric data, a smart BioIntelliSense's BioButton™ medical-grade device and
HIPAA-compliance data service will be used. This enables effortless remote,
multi-parameter data capturing that measures vital signs in real time. It comprises a
single disposable on-body sensor for continuous monitoring of temperature, oximeter
readings, respiratory rate, heart rate at rest, body position, sleep and activity state
for 90-days. Alternatively, a similar oximeter / thermometer combination will be
provided.
Assessed symptoms are Fever, Cough, Shortness of Breath, Fatigue, Muscle or body aches,
Headache, New loss of taste, New loss of smell, Congestion or runny nose, Nausea,
Vomiting, Diarrhea. Each patient will have a composite score ranging from 0-36/day.
1. Symptom Resolution: Fever [Time Frame: 35 days] The number of days required to reach
a score of 0 from the symptom category of fever based on a 0-3 scale: 0 = ≤98.6oF, 1
= >98.6 oF - 100.4 oF, 2 = > 100.4 oF - 102.6 oF, 3 = >102.6 oF
2. Symptom Resolution: Cough [Time Frame: 35 days] The number of days required to reach
a score of 0 from the symptom category of cough based on a 0-2 scale: 0 = no cough,
1 = mild/moderate, 2 = severe (How does the individual discriminate between mild and
moderate?)
3. Symptom Resolution: Shortness of Breath [Time Frame: 35 days] The number of days
required to reach a score of 0 from the symptom category of shortness of breath
based on a 0-3 scale: 0 = no shortness of breath, 1 = with moderate intensity
exercise 2 = with walking on flat surface 3 = short of breath with getting dressed
or daily activities
4. Symptom Resolution: Fatigue [ Time Frame: 35 days] The number of days required to
reach a score of 0 from the symptom category of fatigue based on a 0-3 scale:) 0=no
fatigue, 1=mild fatigue, 2=moderate fatigue, 3=severe fatigue.
5. Symptom Resolution: Muscle/body aches [ Time Frame: 35 days] The number of days
required to reach a score of 0 from the symptom category of muscle/body aches based
on a 0-3 scale: 0=no muscle/body aches, 1=mild muscle/body aches, 2=moderate
muscle/body aches , 3=severe muscle/body aches.
6. Symptom Resolution: Headache [ Time Frame: 35 days] The number of days required to
reach a score of 0 from the symptom category of headache based on a 0-3 scale: 0=no
headache, 1=mild headache, 2=moderate headache, 3=severe headache.
7. Symptom Resolution: New loss of taste [ Time Frame: 35 days] The number of days
required to reach a score of 0 from the symptom category of new loss of taste based
on a binary scale: 0=no loss of taste, 1= loss of taste.
Symptom Resolution: New loss of smell [ Time Frame: 35 days] The number of days
required to reach a score of 0 from the symptom category of new loss of smell based
on a binary scale: 0=no loss of smell, 1= loss of smell.
8. Symptom Resolution: Congestion/ runny nose [ Time Frame: 35 days] The number of days
required to reach a score of 0 from the symptom category of congestion/runny nose on
a 0-3 scale: 0=no congestion/runny nose, 1=mild congestion/runny nose , 2=moderate
congestion/runny nose , 3=severe congestion/runny nose .
9. Symptom Resolution: Nausea [ Time Frame: 35 days] The number of days required to
reach a score of 0 from the symptom category of nausea on a 0-3 scale:0=no nausea,
1=mild nausea, 2=moderate nausea, 3=severe nausea.
10. Symptom Resolution: Vomiting [ Time Frame: 35 days] The number of days required to
reach a score of 0 from the symptom category of vomiting on a 0-3 scale: 0=no
vomiting, 1=mild vomiting, 2=moderate vomiting, 3=severe vomiting.
11. Symptom Resolution: Diarrhea [ Time Frame: 35 days] The number of days required to
reach a score of 0 from the symptom category of diarrhea on a 0-3 scale: 0=no
diarrhea, 1=mild diarrhea, 2=moderate diarrhea, 3=severe diarrhea.
12. Day 28 Composite Symptoms [ Time Frame: 35 days] Total symptom composite score at
day 5 of study supplementation: Symptom categories of fever based on a 0-3 scale: 0
= ≤98.6 oF, 1 = >98.6- 100.6 oF, 2 = > 100.6 - 102.6 oF, 3 = >102 oF; Cough on a 0-3
scale: 0 = no cough, 1 = mild, 2 = moderate, 3 = severe; Shortness of Breath on a
0-3: 0 = no shortness of breath, 1 = with moderate intensity exercise 2 = with
walking on flat surface 3 = short of breath with getting dressed or daily
activities; and Fatigue on a 0-3 scale: 0 = No fatigue/energetic, 1=mild fatigue,
2=moderate fatigue, 3=severe fatigue.
13. Hospitalizations/ER visits [ Time Frame: 35 days] Differences in hospitalization, ER
visits, mortality events between the study arms
14. Severity of Symptoms [Time Frame: 35 days] Differences in severity of symptoms
between study arms
15. Adjunctive Medications [ Time Frame: 35 days] Differences in number of patients who
were prescribed adjunctive medications for their diagnosis between study arms
16. Supplementation Side Effects [ Time Frame: 35 days] Differences in number of
patients in study arms who experienced side effects from the supplements.
Dietary Supplement: CBDRA60 supplement
CBD is a non-psychotropic cannabinoid that has a broad spectrum of well-established
anti-inflammatory and immunomodulatory effects. Red algae (Rhodophyta) are known for
their potent anti-viral properties, non-toxicity and for being well tolerated in humans
[15, 16]. Rhodophyta contain several sulfated polysaccharides that exhibit high antiviral
activity against enveloped viruses.,
Other Name: CBDRA60
Dietary Supplement: Placebo
Placebo
Inclusion Criteria:
The study population will include individuals who tested positive for COVID-19 infection
based on a PCR test. The study population is defined as adults ≥ 18 years of age with no
comorbidities and absence of pre-existing conditions (see exclusion criteria below).
- Baseline drug screen for schedule 1 narcotics
- All participants are required to understand and provide informed consent before any
assessment is performed
- Be willing and able to complete an online questionnaire
- Be able to understand and agrees to comply with planned study procedures and be
available for all study visits
- Participants who have received the Pfizer or Moderna vaccine are allowed to be
enrolled in study if they have a PCR positive test
Exclusion Criteria:
- Current hospitalization
- Participation in any other COVID-19 trial
- Individuals that are taking antiviral medications
- Baseline lab/drug screen shows consumption of a schedule 1 narcotic
- Prior diagnosis of cancer and currently undergoing radiation, chemotherapy, or
immunotherapy; excluding basal cell skin carcinoma
- Participants who have been diagnosed as HIV positive or taking anti-HIV therapy
- Female participants who are pregnant or breastfeeding, lactating, or planning a
pregnancy during the trial.
- Female subjects who is/are breastfeeding or plans to breastfeed
- Medical disease or conditions such as high-risk comorbidities such as: diabetes,
chronic obstructive pulmonary disease (COPD) or emphysema, history of heart attack
or stroke, history of coronary bypass surgery or coronary angioplasty or stent,
history of hospitalization for heart failure, etc.
- Demonstrated inability to comply, tell the truth (as defined by PI, study
investigator on subjects health condition) with the study procedures
- History of hypersensitive or severe allergic reactions
- Anticipated need for immunosuppressive treatment within the next 6 months
- Received immunoglobulins and or any blood or blood products within the 4 months of
being enrolled in this investigation
- Blood dyscrasias or significant disorder of coagulation.
- Severe Liver disease including chronic liver disease, fatty liver, cirrhosis or
awaiting transplant.
- History of alcohol abuse or other recreational drug abuse of schedule 1 narcotics
within 6 months of being enrolled in the study.
- Subjects diagnosed with:
- Kidney disease (CKD) | End-Stage Renal Disease (ESRD) or dialysis.
- A history of Calcium Oxalate kidney stones
- Mineral bone disorders.
Anewsha Therapeutics / Comco R&D
Hanover, Michigan, United States
Investigator: Erin Swartout, MA
Contact: 703-945-7066
erin@anewsha.com
Erin Swartout, MA
7039457066
erin@anewsha.com
Director
chris@anewsha.com
Eleni Stylianou, PHD, Principal Investigator
Anewsha Therapeutics