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

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

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.

Study Overview

• Status: Completed
• Conditions: Pain; Confusion; Covid19; Nausea; Vomiting; Cough; Muscle Weakness; Fever; Headache; Anosmia; Sore Throat; Shortness of Breath; Pain, Joint; Pain, Chest; Irritable Mood; Pain, Abdominal; Pain, Muscle
• Intervention / Treatment: Drug: Hesperidin; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 216
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H1T1C8
      • Montreal Heart Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Montreal Heart Institute
• Collaborators: Ingenew Pharmaceuticals Inc.
• Investigators: Principal Investigator: Jocelyn Dupuis, MD, Montreal Heart Institute

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2021
• Primary Completion (Actual): May 25, 2021
• Study Completion (Actual): June 7, 2021

Study Registration Dates

• First Submitted: January 15, 2021
• First Submitted That Met QC Criteria: January 19, 2021
• First Posted (Actual): January 20, 2021

Study Record Updates

• Last Update Posted (Actual): April 8, 2022
• Last Update Submitted That Met QC Criteria: April 6, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Pain; Neurologic Manifestations; Neurobehavioral Manifestations; Signs and Symptoms, Digestive; Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Musculoskeletal Pain; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Neuromuscular Manifestations; Signs and Symptoms, Respiratory; Sensation Disorders; Olfaction Disorders; COVID-19; Arthralgia; Myalgia; Vomiting; Muscle Weakness; Chest Pain; Abdominal Pain; Headache; Confusion; Dyspnea; Pharyngitis; Anosmia
• Other Study ID Numbers: MHICC-2020-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No