Glucoside- and Rutinoside-rich Crude Material for Relieving Side Effects of COVID-19 Vaccines

Dose-response Study a Glucoside- and Rutinoside-rich Crude Material in Relieving Side Effects of COVID-19 Vaccines

Urgent vaccine development plus the characteristics of the coronavirus have caused the relatively more safety problems in COVID-19 vaccines than other classic vaccines and unavoidably raises more concerns among those who accept or consider to be vaccinated. Mulberry juice consists of a large amount of anthocyanin. The abnormally high interleukin-17A level is frequently seen in patients with inflammation status or diseases with inflammation features. Some specific anthocyanins can reduce cyclooxygenase and nitrogen oxide, and the pharmacological effect of the major anthocyanin in mulberry juice imitates that of interleukin-17A antagonists. These features make mulberry juice a potential crude material for reducing inflammation and pain induced by COVID-19 vaccinations. The investigators propose a randomized control trial to explore the dose-response effects of three different volumes of mulberry juice on the incidence and severity of COVID-19 induced side effects. The findings should be helpful for nutrition supplementation in COVID-19 vaccinations and may improve public coordination of COVID-19 vaccinations.

Study Overview

• Status: Not yet recruiting
• Conditions: Vaccine Adverse Reaction; Side-Effect
• Intervention / Treatment: Dietary supplement: Mulberry juice

Detailed Description

Since the outbreak of Coronavirus Disease-2019 (COVID-19), the size of the infected population continues to expand, and the number of deaths due to the infection continues to climb. Massive vaccination has become the most critical measure to control the pandemic. Vaccination may cause side effects. Urgent vaccine development plus the characteristics of the coronavirus have caused the relatively more safety problems in COVID-19 vaccines than other classic vaccines and unavoidably raises more concerns among those who accept or consider to be vaccinated. Mulberry juice consists of a large amount of anthocyanin. The abnormally high interleukin-17A level is frequently seen in patients with inflammation status or diseases with inflammation features. Previous cell and animal studies have shown that some specific anthocyanins can reduce cyclooxygenase and nitrogen oxide, and the pharmacological effect of the major anthocyanin in mulberry juice imitates that of interleukin-17A antagonists. These features make mulberry juice a potential crude material for reducing inflammation and pain induced by COVID-19 vaccinations. The investigators propose a randomized control trial investigating the dose-response effects of three different volumes of mulberry juice on the incidence and severity of COVID-19 induced side effects and build up initial dose-response models for future reference in nutrition supplementation in COVID-19 vaccinations and improve public coordination of COVID-19 vaccinations.

• Study Type: Interventional
• Enrollment (Anticipated): 93
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: El-Wui Loh, PhD; Phone Number: 0903136037; Email: lohew@hotmail.com
• Study Contact Backup: Name: Yun-Yun Chou, Msc; Phone Number: 0974515039; Email: daliner@tmu.edu.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Concious
• Mentally capable
• Can comunicate using Mendalin or Taiwanese dialet
• Agree to join the current trial

Exclusion Criteria:

• Unable to read the google sheets
• dysphagia
• > 65 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low volume mulberry juice; 10 ml mulberry juice containing about 48 mg polyphenols	Dietary supplement: Mulberry juice; Mulberry is a common macrophanerophyte that can be found in fields or farms. Mulberry fruits contain a large amount of anthocyanins and a relatively small amount of pro-anthocyanins. The plant is easy to grow and the fruit price is low compared with other types of plants producing anthocyanins, and thus a reliable source for anthocyanin supplements. Current laboratory evidence has shown that specific anthocyanins can reduce inflammation status, and potentially thrombosis. One of the enzymes inhibited by specific anthocyanins is cyclooxygenase which catalyzes the synthesis of prostanoids, including thromboxane and prostaglandins. Moreover, a critical study has shown that cyanidin 3-O-glucoside, the main anthocyanin in mulberry fruit, is an allosteric regulator of interleukin-17A.
Experimental: Middle volume mulberry juice; 50 ml mulberry juice containing about 240 mg polyphenols	Dietary supplement: Mulberry juice; Mulberry is a common macrophanerophyte that can be found in fields or farms. Mulberry fruits contain a large amount of anthocyanins and a relatively small amount of pro-anthocyanins. The plant is easy to grow and the fruit price is low compared with other types of plants producing anthocyanins, and thus a reliable source for anthocyanin supplements. Current laboratory evidence has shown that specific anthocyanins can reduce inflammation status, and potentially thrombosis. One of the enzymes inhibited by specific anthocyanins is cyclooxygenase which catalyzes the synthesis of prostanoids, including thromboxane and prostaglandins. Moreover, a critical study has shown that cyanidin 3-O-glucoside, the main anthocyanin in mulberry fruit, is an allosteric regulator of interleukin-17A.
Experimental: High volume mulberry juice; 100 ml mulberry juice containing about 480 mg polyphenols	Dietary supplement: Mulberry juice; Mulberry is a common macrophanerophyte that can be found in fields or farms. Mulberry fruits contain a large amount of anthocyanins and a relatively small amount of pro-anthocyanins. The plant is easy to grow and the fruit price is low compared with other types of plants producing anthocyanins, and thus a reliable source for anthocyanin supplements. Current laboratory evidence has shown that specific anthocyanins can reduce inflammation status, and potentially thrombosis. One of the enzymes inhibited by specific anthocyanins is cyclooxygenase which catalyzes the synthesis of prostanoids, including thromboxane and prostaglandins. Moreover, a critical study has shown that cyanidin 3-O-glucoside, the main anthocyanin in mulberry fruit, is an allosteric regulator of interleukin-17A.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of body temperature	Daily body temperature of each participant is recorded to obtain serial temperatures including body temperature before vaccination (first day) and body temperatures after vaccination (second, third, and fourth day).	Up to four days
Number of participants with fever	Event of 38 degrees celsius or above	Up to four days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with sign cluster 1 (multiple choices)	Redness, swelling, pain, lump or mass, or rash and itching at the injection site; axillary swelling and tenderness at the injection arm; axillary swelling and tenderness at the non-injection arm; none	Up to three days
Number of participants with sign cluster 2 (multiple choices)	Chills, headache, muscle pain, joint pain, fatigue, rash on the body, asthma or breathing difficulty, loss of appetite, nausea or vomiting, diarrhea, stomach ache, insomnia, or drownsiness; none	Up to three days

Collaborators and Investigators

• Sponsor: Taipei Medical University
• Investigators: Principal Investigator: El-Wui Loh, PhD, Taipei Medical University Shuang Ho Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): May 31, 2022
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): May 31, 2023

Study Registration Dates

• First Submitted: May 19, 2022
• First Submitted That Met QC Criteria: May 20, 2022
• First Posted (Actual): May 24, 2022

Study Record Updates

• Last Update Posted (Actual): May 24, 2022
• Last Update Submitted That Met QC Criteria: May 20, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Inflammation; Pain; COVID-19; IL-17; Mulberry; Vaccine Adverse Reaction; Side Effect
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: N202202030

Drug and device information, study documents

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