Efficacy of Mouthwash in Reducing Salivary Carriage of COVID-19

NCT ID: NCT04603794

Last Updated: 2020-10-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-10-01

Study Completion Date

2020-11-30

Brief Summary

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Researchers know that the virus that causes COVID-19 has been found in the saliva (spit) of individuals who exhibit signs of the disease. Investigators would like to test the ability of three mouthwashes to reduce the levels of this virus in participants' mouths. Investigators will ask participants to use a liquid to swish around in the mouth for 30 seconds and spit it into a collection cup. Investigators will also collect spit from participants before and after participants use the mouthwash. Although participants will have no direct benefits from the study, investigators will gain a wealth of information that would benefit patients who are at risk for COVID-19.

Detailed Description

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Project aims:

Aim 1: To examine the salivary carriage of COVID-19 in individuals before and after use of mouthwashes known to reduce oral microbiota, using real time reverse transcriptase quantitative PCR (Polymerase Chain Reaction) to quantify viral load.

RESEARCH STRATEGY:

A. Recruitment and baseline data:

This is a cross-sectional interventional 4 arm study. 60 subjects between 18-80 years of age will be recruited from those who are being treated for COVID-19 at the Ohio State University Medical Center. There is no data upon which to base sample size estimates, and investigators have landed on this number in an effort to obtain a representative sample of Ohio's population. If the potential subject is interested in participating, the study coordinator will collect contact information from the candidate and the consent form will be presented to these individuals. Subjects will be allowed sufficient time to read and ask questions, and once sign these forms, a detailed history including information about ethnicity, education, income, age, sex, race, medical status (including pregnancy) and dental history will be elicited. Subjects will self-collect saliva in a 5 ml collection tube, following which they will be asked to use one of 3 mouthwashes (chlorhexidine, povidone iodine, hydrogen peroxide or control(saline) for thirty seconds and spit them into collection tubes. Investigators will use Peridex, Hydrogen Peroxide and Betadine, which are commercially available formulations of chlorhexidine, hydrogen peroxide and betadine respectively, to reduce formulation bias. Investigators have attached the product labels as appendices to this proposal. The exact mouthwash will be decided by random chance using a random number generator. Investigators have generated the following randomization schedule using Microsoft excel: Each subject will be assigned a number as they are recruited (E.g. first patient to sign the consent will be patient 1, and the second will be patient 2 and so on). Patients 1 and 2 will receive saline and 3 will receive chlorhexidine etc. base on the above randomization schedule. Subjects will then collect saliva in separate collection tubes 15 and 30 minutes after rinsing.

B. Sample collection Saliva will be collected using a methodology described by previous investigators. Briefly, subjects will be asked to collect saliva in their mouth for 3 minutes and then continuously drool into a tube for 3 minutes. This method will allow investigators to collect unstimulated saliva. Saliva will be collected using kits containing RNA (Ribonucleic Acid) stabilizer (Oragen RNA kit).

C. Measurement / Instrumentation

Total RNA will be isolated from saliva using the mirVana miRNA (Messenger Ribonucleic Acid) isolation kit (Applied Biosystems). Microbial cells will be lysed and RNA will be extracted by Acid-Phenol:Chloroform and ethanol precipitation and eluted in nuclease-free water. Investigators will use well validated primers to quantify copy numbers of COVID-19 spike protein mRNA (Messenger Ribonucleic Acid) from the saliva. For an absolute quantification of COVID-19, investigators will use one step RT-PCR (Reverse Transcriptase) assay by using an appropriate commercially available kit. In this step investigators will convert mRNA to cDNA (complementary Deoxyribonucleic Acid) and then quantify the cDNA by using targeted primers and then copy numbers of the COVID-19 will be calculated by comparing ct (cycle threshold)Values samples against standard curve. In order to generate standard curves for absolute quantification, target genes will be amplified with PCR. The PCR products will be cloned into suitable vector. Then plasmids will be extracted, serially diluted, and used as templates in qPCR (quantitative polymerase chain reaction) for generating standard curves.

D. Internal Validity Subjects will be recruited randomly through voluntary participation. This will eliminate presentation bias.

E. Data Analysis

Descriptive statistics will be provided as estimates of salivary carriage of COVID-19. Frequency of salivary carriage of the virus will be expressed as a percent of the total sample population. Reduction in COVID-19 following mouthwash use will be expressed as fold change and compared between the three mouthwash groups using parametric tests.

Conditions

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COVID-19

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This randomized, cross-sectional, double blinded, negative controlled, four armed, prospective, interventional study compared Normal Saline, Hydrogen Peroxide, Chlorhexidine and Povidone-Iodine Mouth Rinses in 60 subjects being treated for Covid 19 at the The Ohio State University Medical Center. Real time reverse transcriptase quantitative PCR measured viral loads.
Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
Double Blinded. All mouthwash vials are masked.

Study Groups

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1% Hydrogen Peroxide Mouth Rinse

30 second oral rinse with 1% Hydrogen Peroxide

Group Type ACTIVE_COMPARATOR

1% Hydrogen Peroxide

Intervention Type DRUG

Commercially Available Over the Counter Standard Formulations USP (United States Pharmacopeia)

0.12% Chlorhexidine Gluconate Mouth Rinse

30 second oral rinse with 0.12% Chlorhexidine Gluconate

Group Type ACTIVE_COMPARATOR

0.12% Chlorhexidine Gluconate Mouth Rinse

Intervention Type DRUG

Commercially Available Mouth Rinses

0.5% Povidone Iodine Mouth Rinse

30 second oral rinse with 0.5% Povidone Iodine Mouth wash

Group Type ACTIVE_COMPARATOR

0.5% Povidone Iodine

Intervention Type DRUG

Commercially Available Mouth Rinses and Over the Counter Standard Formulations

0.9% Normal Saline Mouth Rinse

30 second oral rinse with 0.9% Normal Saline

Group Type PLACEBO_COMPARATOR

0.9% Normal Saline

Intervention Type DRUG

Commercially Available Over the Counter Standard Formulations USP (United States Pharmacopeia)

Interventions

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0.5% Povidone Iodine

Commercially Available Mouth Rinses and Over the Counter Standard Formulations

Intervention Type DRUG

0.12% Chlorhexidine Gluconate Mouth Rinse

Commercially Available Mouth Rinses

Intervention Type DRUG

1% Hydrogen Peroxide

Commercially Available Over the Counter Standard Formulations USP (United States Pharmacopeia)

Intervention Type DRUG

0.9% Normal Saline

Commercially Available Over the Counter Standard Formulations USP (United States Pharmacopeia)

Intervention Type DRUG

Other Intervention Names

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Betadine Mouthwash Peridex Hydrogen Peroxide Salt Water

Eligibility Criteria

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Inclusion Criteria

1. adults age 18-80 admitted to The Ohio State University Medical Center,
2. diagnosis of COVID-19 confirmed by Polymerase Chain Reaction (PCR),
3. salivary carriage of COVID-19 virus
4. ability to perform mouthwash rinses and to expectorate.

Exclusion Criteria

1. allergy to any study mouth rinse,
2. active uncontrolled thyroid disease,
3. pregnancy
4. patients undergoing radioactive iodine therapy.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ohio State University

OTHER

Sponsor Role lead

Responsible Party

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David Hall

Associate Professor, Hospital Attending

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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David L Hall, DDS

Role: STUDY_DIRECTOR

The Ohio State University College of Dentistry

Locations

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The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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David L Hall, DDS

Role: CONTACT

614-292-2622

Purnima Kumar, PhD,DDS

Role: CONTACT

614-804-2112

Facility Contacts

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David L Hall, DDS

Role: primary

614-292-2622

Purnima Kumar, PhD,DDS

Role: backup

614-804-2112

References

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Serban D, Banu A, Serban C, Tuta-Sas I, Vlaicu B. Predictors of quantitative microbiological analysis of spatter and aerosolization during scaling. Rev Med Chir Soc Med Nat Iasi. 2013 Apr-Jun;117(2):503-8.

Reference Type BACKGROUND
PMID: 24340537 (View on PubMed)

Gupta G, Mitra D, Ashok KP, Gupta A, Soni S, Ahmed S, Arya A. Efficacy of preprocedural mouth rinsing in reducing aerosol contamination produced by ultrasonic scaler: a pilot study. J Periodontol. 2014 Apr;85(4):562-8. doi: 10.1902/jop.2013.120616. Epub 2013 Jul 15.

Reference Type BACKGROUND
PMID: 23855840 (View on PubMed)

Shetty SK, Sharath K, Shenoy S, Sreekumar C, Shetty RN, Biju T. Compare the effcacy of two commercially available mouthrinses in reducing viable bacterial count in dental aerosol produced during ultrasonic scaling when used as a preprocedural rinse. J Contemp Dent Pract. 2013 Sep 1;14(5):848-51. doi: 10.5005/jp-journals-10024-1414.

Reference Type BACKGROUND
PMID: 24685786 (View on PubMed)

Devker NR, Mohitey J, Vibhute A, Chouhan VS, Chavan P, Malagi S, Joseph R. A study to evaluate and compare the efficacy of preprocedural mouthrinsing and high volume evacuator attachment alone and in combination in reducing the amount of viable aerosols produced during ultrasonic scaling procedure. J Contemp Dent Pract. 2012 Sep 1;13(5):681-9. doi: 10.5005/jp-journals-10024-1209.

Reference Type BACKGROUND
PMID: 23250175 (View on PubMed)

Klyn SL, Cummings DE, Richardson BW, Davis RD. Reduction of bacteria-containing spray produced during ultrasonic scaling. Gen Dent. 2001 Nov-Dec;49(6):648-52.

Reference Type BACKGROUND
PMID: 12024755 (View on PubMed)

Wirthlin MR, Choi JH, Kye SB. Use of chlorine dioxide mouthrinse as the ultrasonic scaling lavage reduces the viable bacteria in the generated aerosols. J West Soc Periodontol Periodontal Abstr. 2006;54(2):35-44. No abstract available.

Reference Type BACKGROUND
PMID: 17214015 (View on PubMed)

Peng X, Xu X, Li Y, Cheng L, Zhou X, Ren B. Transmission routes of 2019-nCoV and controls in dental practice. Int J Oral Sci. 2020 Mar 3;12(1):9. doi: 10.1038/s41368-020-0075-9.

Reference Type BACKGROUND
PMID: 32127517 (View on PubMed)

Navazesh M. Methods for collecting saliva. Ann N Y Acad Sci. 1993 Sep 20;694:72-7. doi: 10.1111/j.1749-6632.1993.tb18343.x. No abstract available.

Reference Type BACKGROUND
PMID: 8215087 (View on PubMed)

To KK, Tsang OT, Yip CC, Chan KH, Wu TC, Chan JM, Leung WS, Chik TS, Choi CY, Kandamby DH, Lung DC, Tam AR, Poon RW, Fung AY, Hung IF, Cheng VC, Chan JF, Yuen KY. Consistent Detection of 2019 Novel Coronavirus in Saliva. Clin Infect Dis. 2020 Jul 28;71(15):841-843. doi: 10.1093/cid/ciaa149.

Reference Type BACKGROUND
PMID: 32047895 (View on PubMed)

Chaudhary P, Melkonyan A, Meethil A, Saraswat S, Hall DL, Cottle J, Wenzel M, Ayouty N, Bense S, Casanova F, Chaney M, Chase H, Hermel R, McClement M, Sesson C, Woolsey B, Kumar P. Estimating salivary carriage of severe acute respiratory syndrome coronavirus 2 in nonsymptomatic people and efficacy of mouthrinse in reducing viral load: A randomized controlled trial. J Am Dent Assoc. 2021 Nov;152(11):903-908. doi: 10.1016/j.adaj.2021.05.021. Epub 2021 Jun 11.

Reference Type DERIVED
PMID: 34561086 (View on PubMed)

Related Links

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https://doi.org/10.21203/rs.3.rs-34544/v2

Povidone-iodine demonstrates rapid in-vitro Activity...

https://doi.org/10.1016/j.ijid.2020.05.030

Viral dynamics in asymptomatic patients with COVID-19

Other Identifiers

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2020H0346

Identifier Type: -

Identifier Source: org_study_id