Clinical trial NCT04748783: Antiviral Efficacy and Acceptability of Mouth Rinses for Inactivation of COVID-19
Official title: Antiviral Efficacy and Acceptability of Therapeutic Antiseptic Mouth Rinses for Inactivation of COVID SARS-2 Virus
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: COVID19
Coronavirus Infection
SARS CoV-2 Infection
Keywords: Inactivation of SARS CoV-2 Virus
Antiseptic Mouth Rinses
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Colgate Palmolive
First posted: 2021-02-10
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, placebo-controlled, double-blind prospective trial to test the efficacy and acceptability of 4 therapeutic, antiseptic mouth rinses to inactivate SARS-CoV-2 virus in saliva of COVID-19 positive patients
Primary purpose: TREATMENT

Brief summary: Subjects (125) will be randomized to one of five mouthrinses and will be asked to give a saliva sample immediately before and after a 30-60 second mouthwash.

Saliva samples will be collected from subjects at 15-minute intervals thereafter up to one hour (15, 30, 45 and 60 min). The saliva will be used for RT-PCR detection of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) and viral infectivity assays, along with quantitative cytokine and chemokine concentration (pg/mL, Luminex).

Subjects will complete a short survey on the taste and experience of using the mouthwash.

Peripheral blood will be collected at the end of salivary collection. Subjects, except controls, will be provided materials and oral hygiene instruction related to daily use of oral hygiene products. In the seven-day period between study visit one and study visit two, subjects will be directed to brush with Colgate toothpaste (at least twice per day) and rinse with the Colgate mouthrinse (according to on-label procedures). Controls are asked to carry out their typical oral hygiene regimen with the products they typically use.

All subjects keep a daily diary of oral hygiene performance, product usage, COVID-19 symptoms and exposures. Subjects complete study visit two one week after the baseline visit during which additional salivary (1 time point, 2 mL of saliva over 5 min, no rinse) will occur and blood samples collected. each subject will undergo a periodontal exam.

Detailed description: Randomized, double-blind prospective trial to test the efficacy and acceptability of therapeutic, antiseptic mouth rinses to inactivate SARS-CoV-2 virus in saliva of SARS-CoV-2+ patients 18-65 years of age. The study will enroll 30 outpatient SARS-CoV-2+ subjects per mouth rinse, (to achieve a total of 25 subjects with full data sets per mouth rinse,) with 5 mouth rinses, requiring us to enroll 125 SARS-CoV-2+ patients. Patients will be randomized to their mouthrinse. These patients will have already had a confirmed SARS-CoV-2+ test prior to enrollment. There will be no stratification to our randomization. All mouthrinses are commercially available Colgate products and will be used according to on-label instructions.

Subjects will be randomized to a mouthrinse and will be asked to give a saliva sample immediately before and after a 30-60 second mouthwash.

Saliva samples will be collected from subjects at 15-minute intervals thereafter up to one hour (15, 30, 45 and 60 min). The saliva samples will be stored and used for RT-PCR detection of SARS-CoV-2 virus and viral infectivity assays, along with quantitative cytokine and chemokine concentration (pg/mL, Luminex).

Subjects will also complete a short survey on the taste and experience of using the mouthwash.

Peripheral blood will be collected at the end of salivary collection. Subjects, except controls, will be provided materials and oral hygiene instruction related to daily use of oral hygiene products provided by the study. In the seven-day period between study visits, subjects will be directed to brush with Colgate toothpaste (at least twice per day) and rinse with the Colgate mouthrinse (according to on-label procedures). Controls are not given Colgate products and will be asked to carry out their typical oral hygiene regimen with the products they typically use. All subjects will be asked to keep a daily diary of oral hygiene performance, product usage, COVID-19 symptoms and exposures.

Subjects will be scheduled to return to the research clinic at one week after the baseline assessment, during which additional salivary (1 time point, 2 mL of saliva over 5 min, no rinse will occur) and blood samples will be collected. At the conclusion of sample collection, the subject will undergo a periodontal exam. Study participation concludes following the periodontal exam at the end of the second on site study visit. Patients with any periodontitis or gingivitis diagnosis will be informed of their diagnosis and will be referred to an oral healthcare provider for further treatment. This study involves two 90-minute visits.

Eligibility criteria: Inclusion Criteria:

Subjects must meet all of the following inclusion criteria to be eligible for enrollment in the study:

* Diagnosed SARS-CoV-2+ status. Either became symptomatic in the prior 7 days, or if not symptomatic, likely infected/exposed within the prior 7 days. All patients listed from the University of North Carolina at Chapel Hill (UNC) Respiratory Diagnostic Center (RDC) have a confirmed SARS-CoV-2 infection and have consented to be contacted for research purposes. For patients contacting study coordinators for enrollment, who were not tested in the RDC, they must provide written proof of positive SARS-CoV-2 status in the prior 7 days.
* Individuals (all sex, all gender) at least 18 years of age and at most 65 years of age and in good oral health without any known allergies to commercial dental products or cosmetics. American Society of Anaesthesiologists (ASA) class I or II prior to SARS-CoV-2 infection.
* Evidence of a personally signed and dated informed consent document indicating the subject (or legally acceptable representative) has been informed of all pertinent aspects of the trial and all of their questions have been answered.
* Able to comprehend and follow the requirements of the study (including availability on scheduled visit dates) based on research site personnel's assessment.
* Females of childbearing potential will have a negative urine pregnancy test (on site) or be physically incapable of pregnancy (implants or injections, Intrauterine device, Bilateral tubal ligation, Hysterectomy, Ovariectomy, Women post-menopausal)

Exclusion Criteria:

Subjects presenting with any of the following will not be included in the study:

* Patients who have been eating or drinking within an hour of the study
* Patients under 18 years of age and older than 65 years of age
* Subjects presenting with and/or self-reporting any of the following will not be included in the study:

  * history of significant adverse effects following use of oral hygiene products such as toothpastes and mouthrinses. (self-reported)
  * Self-reported allergy to hydrogen peroxide, peroxyl, chlorhexidine gluconate, periogard, peridex, colgate total zero, colgate total, cetylpyridinium chloride, essential oils (Eucalyptol, Menthol, Methyl salicylate, Thymol), and other components in the mouth rinses (methyl salicylate, ethanol, saccharin sodium, glycerin, propylene glycol, sorbitol, Federal Food, Drug, and Cosmetic (FD\&C) blue additive no. 1, Poloxamer 407, Benzoic acid, Zinc chloride, Sodium benzoate, Sucralose, Polyethylene Glycol (PEG-40) sorbitan diisostearate, potassium sorbate, citric acid).
  * History of serious medical conditions that, at the discretion of the Investigator, will disqualify the subject. (Self-reported)
  * A history of severe dry mouth (xerostomia), severe drug-induced xerostomia (antidepressants, anticonvulsants, antihypertensives), or Sjogren's syndrome
  * A history of recent (within the last 30 days) or current recent oral herpes flare up, candida (thrush) infection, apthous ulcer flare up, current/active severe periodontal disease, or other recent oral viral infection or flare up within the past 30 days (self-reported)
  * Current history of alcohol or drug abuse (self-reported).
  * History of drinking water or eating food within an hour of the study visit.
  * History of drinking alcohol within 12 hours of the study visit.
  * History of using a commercial mouthrinse within 24 hours of the study visit.
  * Participation in any study involving oral care products, concurrently or within the previous 30 days. (self-reported)
  * Positive pregnancy test reported pregnancy or lactation (this criterion is due to oral tissue changes related to pregnancy and nursing which can affect interpretation of study results. Additionally, women are advised to check with their physician before using Chlorhexidine Gluconate during pregnancy and lactation, which cannot occur in a blinded, randomized trial.)
  * Other severe acute or chronic medical or psychiatric conditions or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this trial.
  * Patient with developmental/cognitive disability that cannot self-consent, comprehend and follow the requirements of the study based on research site personnel's assessment.
  * Patients with sizable mucosal tears, abrasions, growths or burns in the mouth
  * Patients with kidney dysfunction

Primary outcomes:
measure: Change in Reverse Transcription Polymerase Chain Reaction (RT-PCR) Baseline to 15 Min
timeFrame: Baseline, 15 minutes
measure: Change in Reverse Transcription Polymerase Chain Reaction (RT-PCR) From Baseline to 30 Minutes
timeFrame: Baseline, 30 Minutes
measure: Change in Reverse Transcription Polymerase Chain Reaction (RT-PCR) From Baseline to 45 Minutes
timeFrame: Baseline, 45 Minutes
measure: Change in Reverse Transcription Polymerase Chain Reaction (RT-PCR) From Baseline to 60 Minutes
timeFrame: Baseline, 60 minutes
measure: Change in Reverse Transcription Polymerase Chain Reaction (RT-PCR) From Baseline to 1-week.
timeFrame: Baseline, 1 week
Secondary outcomes:
measure: Change in Saliva Cytokine Concentration
timeFrame: Baseline, 1 week
measure: Change in Blood Cytokine Concentration
timeFrame: Baseline, 1 week
measure: Change in Saliva Chemokine Concentration
timeFrame: Baseline, 1 week
measure: Change in Blood Chemokine Concentration
timeFrame: Baseline, 1 week
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: Adams School of Dentistry
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Laura a Jacox, DMD, PhD, MS
role: PRINCIPAL_INVESTIGATOR
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