Study of Hesperidin Therapy on COVID-19 Symptoms (HESPERIDIN)

Study Overview
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Brief Summary
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The main aim of this study is to determine the effects of short-term treatment with hesperidin on COVID-19 symptoms in comparison with a placebo. Treatment effects will be observed through a symptoms diary that will be completed by participants throughout the study and by taking the oral temperature daily.

Detailed Description
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This will be a randomized, double-blind, placebo-controlled study. The study will include subjects from Quebec diagnosed with COVID-19 infections. Following informed consent, 216 subjects meeting all inclusion and no exclusion criteria will be randomized to receive either hesperidin 1000 mg once daily (q.d.)) or placebo (1:1 allocation ratio) for 14 days. Investigational drug will be delivered to the patients' homes with an electronic oral thermometer and a symptoms diary. Follow-up phone assessments will occur after 3, 7, 10, and 14 days following randomization for evaluation of COVID-19 symptoms. Electronic Case Report Form (eCRF) will be completed by the research personnel over the phone with the patients. The symptoms diary will be mailed back to the coordinating center at the end of the study in a pre-addressed envelope.

Official Title
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A Phase 2, Randomized, Double-blind, Placebo-controlled Study of Hesperidin Therapy on COVID-19 Symptoms: The Hesperidin Coronavirus Study (Hesperidin)

Conditions
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Covid19, Anosmia, Fever, Cough, Shortness of Breath, Sore Throat, Nausea, Vomiting, Headache, Muscle Weakness, Pain, Muscle, Pain, Chest, Pain, Joint, Pain, Abdominal, Pain, Irritable Mood, Confusion

Intervention / Treatment
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* Drug: Hesperidin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Covid-19 positive by polymerase chain reaction (PCR) testing; Participant must be able to evaluate their symptoms and report them in the symptoms diary; Patients must be able to take their oral temperature daily with an electronic thermometer provided to them with study materials; Males and females, at least 18 years of age, capable and willing to provide informed consent; Female patient is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile, or is of childbearing potential and practicing at least one method of contraception and preferably two complementary forms of contraception including a barrier method (e.g. male or female condoms, spermicides, sponges, foams, jellies, diaphragm, intrauterine device (IUD)) throughout the study; Patient must have received a diagnosis of COVID-19 infection within the last 48 hours and have one or more symptoms; Outpatient setting (not currently hospitalized or under immediate consideration for hospitalization); Patient must be able and willing to comply with the requirements of this study protocol. Exclusion Criteria: Patient currently hospitalized or under immediate consideration for hospitalization; Patient currently in shock or with hemodynamic instability; Patient undergoing chemotherapy for cancer; Patient is unable to take oral temperature using an electronic thermometer; Patient who received at least one dose of the COVID-19 vaccine; Female patient who is pregnant or breast-feeding or is considering becoming pregnant during the study; People taking anticoagulant/antiplatelet medications, those with bleeding disorders, and people two weeks before or after surgery; Patient is considered by the investigator, for any reason, to be an unsuitable candidate for the study; Regular consumption of natural products containing more than 150 mg of hesperidin or regular consumption of more than 1 glass of orange juice per day; Known allergy to any of the medicinal and non-medicinal ingredient: hesperidin, microcrystalline cellulose, magnesium stearate.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hesperidin 1000mg<br>Patients will receive study medication Hesperidin and will take 2 capsules of 500mg at the same time in the evening, at bedtime with water. | Drug: Hesperidin<br>* Patients will receive study medication Hesperidin and will take 2 capsules of 500mg at the same time in the evening, at bedtime with water.<br>|
| Placebo Comparator: Placebo 1000mg<br>Patients will receive study medication Placebo and will take 2 capsules of 500mg at the same time in the evening, at bedtime with water. | Drug: Placebo<br>* Patients will receive study medication Placebo and will take 2 capsules of 500mg at the same time in the evening, at bedtime with water.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With COVID-19 Symptoms at Day 3. | Number of subjects with any of the following COVID-19 symptoms: fever (temperature > 38 degrees), cough, shortness of breath or anosmia, at day 3. | Day 3 | 
| Number of Subjects With COVID-19 Symptoms at Day 7. | Number of subjects with any of the following COVID-19 symptoms: fever (temperature > 38 degrees), cough, shortness of breath or anosmia, at day 7. | Day 7 | 
| Number of Subjects With COVID-19 Symptoms at Day 10. | Number of subjects with any of the following COVID-19 symptoms: fever (temperature > 38 degrees), cough, shortness of breath or anosmia, at day 10. | Day 10 | 
| Number of Subjects With COVID-19 Symptoms at Day 14. | Number of subjects with any of the following COVID-19 symptoms: fever (temperature > 38 degrees), cough, shortness of breath or anosmia, at day 14. | Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Number of COVID-19 Symptoms at Day 3. | Mean number of COVID-19 symptoms (range 0-13) at day 3. | Day 3 | 
| Mean Number of COVID-19 Symptoms at Day 7. | Mean number of COVID-19 symptoms (range 0-13) at day 7. | Day 7 | 
| Mean Number of COVID-19 Symptoms at Day 10. | Mean number of COVID-19 symptoms (range 0-13) at day 10. | Day 10 | 
| Mean Number of COVID-19 Symptoms at Day 14. | Mean number of COVID-19 symptoms (range 0-13) at day 14. | Day 14 | 
| Number of Subjects With Complete Disappearance of Any Symptom. | The descriptive statistics are the number of participants having complete disappearance of any symptom. | From randomization to occurence of first event, assessed up to 14 days | 
| Number of Subjects With the Cough Symptom. | Number of subjects with the cough symptom at day 3. | Day 3 | 
| Number of Subjects With the Cough Symptom. | Number of subjects with the cough symptom at day 7. | Day 7 | 
| Number of Subjects With the Cough Symptom. | Number of subjects with the cough symptom at day 10. | Day 10 | 
| Number of Subjects With the Cough Symptom. | Number of subjects with the cough symptom at day 14. | Day 14 | 
| Number of Subjects With the Presence of Fever. | Number of subjects with the presence of fever (temperature > 38 degrees) at day 3. | Day 3 | 
| Number of Subjects With the Presence of Fever. | Number of subjects with the presence of fever (temperature > 38 degrees) at day 7. | Day 7 | 
| Number of Subjects With the Presence of Fever. | Number of subjects with the presence of fever (temperature > 38 degrees) at day 10. | Day 10 | 
| Number of Subjects With the Presence of Fever. | Number of subjects with the presence of fever (temperature > 38 degrees) at day 14. | Day 14 | 
| Number of Subjects With the Presence of Shortness of Breath. | Number of subjects with the presence of shortness of breath at day 3. | Day 3 | 
| Number of Subjects With the Presence of Shortness of Breath. | Number of subjects with the presence of shortness of breath at day 7. | Day 7 | 
| Number of Subjects With the Presence of Shortness of Breath. | Number of subjects with the presence of shortness of breath at day 10. | Day 10 | 
| Number of Subjects With the Presence of Shortness of Breath. | Number of subjects with the presence of shortness of breath at day 14. | Day 14 | 
| Number of Subjects With the Presence of Anosmia. | Number of subjects with the presence of anosmia at day 3. | Day 3 | 
| Number of Subjects With the Presence of Anosmia. | Number of subjects with the presence of anosmia at day 7. | Day 7 | 
| Number of Subjects With the Presence of Anosmia. | Number of subjects with the presence of anosmia at day 10. | Day 10 | 
| Number of Subjects With the Presence of Anosmia. | Number of subjects with the presence of anosmia at day 14. | Day 14 | 
| Number of Subjects With the Presence of Feverish or Chills. | Number of subjects with the presence of feverish or chills at day 3. | Day 3 | 
| Number of Subjects With the Presence of Feverish or Chills. | Number of subjects with the presence of feverish or chills at day 7. | Day 7 | 
| Number of Subjects With the Presence of Feverish or Chills. | Number of subjects with the presence of feverish or chills at day 10. | Day 10 | 
| Number of Subjects With the Presence of Feverish or Chills. | Number of subjects with the presence of feverish or chills at day 14. | Day 14 | 
| Number of Subjects With the Presence of Sore Throat. | Number of subjects with the presence of sore throat at day 3. | Day 3 | 
| Number of Subjects With the Presence of Sore Throat. | Number of subjects with the presence of sore throat at day 7. | Day 7 | 
| Number of Subjects With the Presence of Sore Throat. | Number of subjects with the presence of sore throat at day 10. | Day 10 | 
| Number of Subjects With the Presence of Sore Throat. | Number of subjects with the presence of sore throat at day 14. | Day 14 | 
| Number of Subjects With the Presence of Runny Nose. | Number of subjects with the presence of runny nose at day 3. | Day 3 | 
| Number of Subjects With the Presence of Runny Nose. | Number of subjects with the presence of runny nose at day 7. | Day 7 | 
| Number of Subjects With the Presence of Runny Nose. | Number of subjects with the presence of runny nose at day 10. | Day 10 | 
| Number of Subjects With the Presence of Runny Nose. | Number of subjects with the presence of runny nose at day 14. | Day 14 | 
| Number of Subjects With the Presence of Nausea/Vomiting. | Number of subjects with the presence of nausea/vomiting at day 3. | Day 3 | 
| Number of Subjects With the Presence of Nausea/Vomiting. | Number of subjects with the presence of nausea/vomiting at day 7. | Day 7 | 
| Number of Subjects With the Presence of Nausea/Vomiting. | Number of subjects with the presence of nausea/vomiting at day 10. | Day 10 | 
| Number of Subjects With the Presence of Nausea/Vomiting. | Number of subjects with the presence of nausea/vomiting at day 14. | Day 14 | 
| Number of Subjects With the Presence of Headache. | Number of subjects with the presence of headache at day 3. | Day 3 | 
| Number of Subjects With the Presence of Headache. | Number of subjects with the presence of headache at day 7. | Day 7 | 
| Number of Subjects With the Presence of Headache. | Number of subjects with the presence of headache at day 10. | Day 10 | 
| Number of Subjects With the Presence of Headache. | Number of subjects with the presence of headache at day 14. | Day 14 | 
| Number of Subjects With the Presence of General Weakness. | Number of subjects with the presence of general weakness at day 3. | Day 3 | 
| Number of Subjects With the Presence of General Weakness. | Number of subjects with the presence of general weakness at day 7. | Day 7 | 
| Number of Subjects With the Presence of General Weakness. | Number of subjects with the presence of general weakness at day 10. | Day 10 | 
| Number of Subjects With the Presence of General Weakness. | Number of subjects with the presence of general weakness at day 14. | Day 14 | 
| Number of Subjects With the Presence of Pain. | Number of subjects with the presence of pain at day 3. | Day 3 | 
| Number of Subjects With the Presence of Pain. | Number of subjects with the presence of pain at day 7. | Day 7 | 
| Number of Subjects With the Presence of Pain. | Number of subjects with the presence of pain at day 10. | Day 10 | 
| Number of Subjects With the Presence of Pain. | Number of subjects with the presence of pain at day 14. | Day 14 | 
| Number of Subjects With the Presence of Irritability/Confusion. | Number of subjects with the presence of irritability/confusion at day 3. | Day 3 | 
| Number of Subjects With the Presence of Irritability/Confusion. | Number of subjects with the presence of irritability/confusion at day 7. | Day 7 | 
| Number of Subjects With the Presence of Irritability/Confusion. | Number of subjects with the presence of irritability/confusion at day 10. | Day 10 | 
| Number of Subjects With the Presence of Irritability/Confusion. | Number of subjects with the presence of irritability/confusion at day 14. | Day 14 | 
| Number of Subjects With the Presence of Diarrhea. | Number of subjects with the presence of diarrhea at day 3. | Day 3 | 
| Number of Subjects With the Presence of Diarrhea. | Number of subjects with the presence of diarrhea at day 7. | Day 7 | 
| Number of Subjects With the Presence of Diarrhea. | Number of subjects with the presence of diarrhea at day 10. | Day 10 | 
| Number of Subjects With the Presence of Diarrhea. | Number of subjects with the presence of diarrhea at day 14. | Day 14 |