Evaluation of Oral Plaque Removal Utilizing an Adjunct Enzyme Pre-rinse

• Sponsor: Indiana University (Other)
• Overall Status: Completed
• CT.gov ID: NCT04512482
• Collaborator: Water Pik, Inc. (Industry), Delta Dental Foundation (Other)
• Enrollment: 46
• Location: 1
• Arms: 2
• Actual Duration (Months): 8.6
• Patients Per Site Per Month: 5.3

Study Details

Study Description

Brief Summary

This study aims to investigate the impact of a bromelain pre-rinse adjunct on oral plaque removal in orthodontic subjects. The study's null hypothesis states that there is no statistically significant difference in visual plaque scores among orthodontic subjects with or without proteolytic enzyme rinse aid.

Condition or Disease	Intervention/Treatment	Phase
Dental Plaque; Dental Caries	Drug: Bromelain; Other: Powdered sugar	Phase 2

Detailed Description

Bromelain, a naturally occurring cysteine protease, from pineapple stalks, is used in food and medical industries and listed on the FDA's "Generally Recognized As Safe" (GRAS) list. In vitro bromelain study demonstrated antibacterial effect on oral pathogens. Bromelain was found to prevent biofilm formation by interfering with bacteria-bacteria adhesion and/or adhesion to enamel surface. Clinical trials with toothpaste containing bromelain demonstrated improved plaque and gingivitis scores and extrinsic enamel stain removal capabilities. The impact of bromelain application prior to traditional mechanisms of plaque removal have not been clearly evaluated.

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Enrolled subjects undergoing orthodontic treatment with fixed appliances will be randomized to receive either the Bromelain rinse or Placebo first and then will be crossed over to receive the opposite intervention. The study will consist of two treatment period (1 day) separated by a washout period of 1 week.Enrolled subjects undergoing orthodontic treatment with fixed appliances will be randomized to receive either the Bromelain rinse or Placebo first and then will be crossed over to receive the opposite intervention. The study will consist of two treatment period (1 day) separated by a washout period of 1 week.
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Masking Description: Investigators were blinded during the clinical phase of the study and were unaware of the agents the subjects received. The investigators were also blinded during the visual plaque score analysis of the project and were unaware of what photograph corresponded to what phase or intervention.
• Primary Purpose: Supportive Care
• Official Title: A Visual Evaluation of Oral Plaque Removal Utilizing an Adjunct Enzyme Pre-rinse in Orthodontic Subjects
• Actual Study Start Date: Jun 14, 2018
• Actual Primary Completion Date: Jul 24, 2018
• Actual Study Completion Date: Mar 4, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental: Bromelain, Then Placebo Subjects were asked to chew a disclosing tablet, swish, and expectorate. Intraoral photographs were obtained. They then received a vial containing 1 gram of bromelain that was reconstituted with 15ml of pineapple juice at 50 degrees F. Subjects swished the solution in their mouth for 2 minutes and then expectorated. Intraoral photographs were obtained. Subjects then received a toothbrush and were asked to brush their teeth for 2 minutes. Intraoral photographs were obtained. The subjects were then given a Waterpik and instructed to use the appliances to clean their teeth and brackets to the best of their ability, for 2 minutes. Intraoral photographs were obtained. After a 1 week washout period, they received the placebo rinse (powdered sugar), following the same protocol and series of intraoral photographs.	Drug: Bromelain; The subjects were randomized to either receive the bromelain pre-rinse or the powdered sugar placebo pre-rinse. Subjects then had a 5-9 day washout period and was then exposed to the other intervention.; Other Names: proteolytic enzyme rinse ; Other: Powdered sugar; The subjects were randomized to either receive the bromelain pre-rinse or the powdered sugar placebo pre-rinse. Subjects then had a 5-9 day washout period and was then exposed to the other intervention.; Other Names: placebo rinse
Placebo Comparator: Experimental: Placebo, Then Bromelain Subjects were asked to chew a disclosing tablet, swish, and expectorate. Intraoral photographs were obtained. They then received a vial containing 1 gram of powdered sugar that was reconstituted with 15ml of pineapple juice at 50 degrees F. Subjects swished the solution in their mouth for 2 minutes and then expectorated. Intraoral photographs were obtained. Subjects then received a toothbrush and were asked to brush their teeth for 2 minutes. Intraoral photographs were obtained. The subjects were then given a Waterpik and instructed to use the appliances to clean their teeth and brackets to the best of their ability, for 2 minutes. Intraoral photographs were obtained. After a 1 week washout period, they received the bromelain rinse, following the same protocol and series of intraoral photographs.	Drug: Bromelain; The subjects were randomized to either receive the bromelain pre-rinse or the powdered sugar placebo pre-rinse. Subjects then had a 5-9 day washout period and was then exposed to the other intervention.; Other Names: proteolytic enzyme rinse ; Other: Powdered sugar; The subjects were randomized to either receive the bromelain pre-rinse or the powdered sugar placebo pre-rinse. Subjects then had a 5-9 day washout period and was then exposed to the other intervention.; Other Names: placebo rinse

Outcome Measures

Primary Outcome Measures

1. Composite Plaque Score [1 day]

   The composite plaque score refers to the cumulative plaque score of all twelve teeth following the administration of the bromelain and placebo (powdered sugar) solutions. The composite plaque score scale had a minimum value of 0 and a maximum value of 48. A score of 0 indicated no plaque was observed on the teeth, while a a score of 48 indicated severe plaque on all possible tooth surfaces. A lower plaque score reflects a better outcome, while a higher plaque score a worse outcome.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years to 25 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• male or female

• 10 to 25 years of age

• willing to consent to participation

• able to follow study instructions

• in active orthodontic treatment with fixed orthodontic appliances

Exclusion Criteria:

• unwilling/unable to follow study instructions

• documented/suspected pineapple allergy

• proteolytic enzyme allergy

• food dye allergy

• smoker

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Indiana University School of Dentistry	Indianapolis	Indiana	United States	46202

Sponsors and Collaborators

• Indiana University
• Water Pik, Inc.
• Delta Dental Foundation

Investigators

• Principal Investigator: Kelton Stewart, DDS, MS, Indiana University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 29, 2018

More Information

Publications

None provided.

• Responsible Party: Kelton Stewart, Chair & Program Director, Department of Orthodontics and, Indiana University
• ClinicalTrials.gov Identifier: NCT04512482
• Other Study ID Numbers: 1802369383
• First Posted: Aug 13, 2020
• Last Update Posted: Dec 3, 2020
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Kelton Stewart, Chair & Program Director, Department of Orthodontics and, Indiana University: proteolytic enzyme; plaque removal; oral hygiene; orthodontic treatment
• Additional relevant MeSH terms: Dental Caries; Dental Plaque

Study Results

Participant Flow

Recruitment Details	Subject recruitment occurred from 6/14/2018 to 7/3/2018 from the graduate orthodontic clinic in the Indiana University School of Dentistry. 46 patients were screened for eligibility during this time frame.
Pre-assignment Detail	46 of 46 subjects were randomized. Of those, 45 subjects completed at least one of the two study interventions (one of the study arms).

Arm/Group Title	Placebo & Bromelain	Bromelain & Placebo
Arm/Group Description	Subjects were asked to chew a disclosing tablet, swish, and expectorate. Intraoral photographs were obtained. They then received a vial containing 1 gram of powdered sugar that was reconstituted with 15ml of pineapple juice at 50 degrees F. Subjects swished the solution in their mouth for 2 minutes and then expectorated. Intraoral photographs were obtained. Subjects then received a toothbrush and were asked to brush their teeth for 2 minutes. Intraoral photographs were obtained. The subjects were then given a Waterpik and instructed to use the appliances to clean their teeth and brackets to the best of their ability, for 2 minutes. Intraoral photographs were obtained. Subjects completed a 1 week (5-9 day) washout period and then completed the protocol again but received the bromelain rinse.	Subjects were asked to chew a disclosing tablet, swish, and expectorate. Intraoral photographs were obtained. They then received a vial containing 1 gram of bromelain that was reconstituted with 15ml of pineapple juice at 50 degrees F. Subjects swished the solution in their mouth for 2 minutes and then expectorated. Intraoral photographs were obtained. Subjects then received a toothbrush and were asked to brush their teeth for 2 minutes. Intraoral photographs were obtained. The subjects were then given a Waterpik and instructed to use the appliances to clean their teeth and brackets to the best of their ability, for 2 minutes. Intraoral photographs were obtained. Subjects completed a 1 week (5-9 day) washout period and then completed the protocol again but received the placebo (powdered sugar).
Period Title: First Intervention (1 Day)
STARTED	24	21
Baseline Plaque Assessment	24	21
Baseline Photographs	24	21
Received Rinse Intervention	24	21
Post-rinse Photographs	24	21
Toothbrush Utilization	24	21
Post-toothbrush Photographs	24	21
Waterpik Utilization	24	21
Post-Waterpik Photographs	24	21
COMPLETED	24	21
NOT COMPLETED	0	0
Period Title: First Intervention (1 Day)
STARTED	24	21
COMPLETED	24	21
NOT COMPLETED	0	0
Period Title: First Intervention (1 Day)
STARTED	24	21
Baseline Plaque Assessment	22	20
Baseline Photographs	22	20
Received Intervention	22	20
Post-rinse Photographs	22	20
Toothbrush Utilization	22	20
Post-toothbrush Photographs	22	20
Waterpik Utilization	22	20
Post-Waterpik Photographs	22	20
COMPLETED	22	20
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	Placebo & Bromelain	Bromelain & Placebo	Total
Arm/Group Description	Subjects were asked to chew a disclosing tablet, swish, and expectorate. Intraoral photographs were obtained. They then received a vial containing 1 gram of powdered sugar (placebo) that was reconstituted with 15ml of pineapple juice at 50 degrees F. Subjects swished the solution in their mouth for 2 minutes and then expectorated. Intraoral photographs were obtained. Subjects then received a toothbrush and were asked to brush their teeth for 2 minutes. Intraoral photographs were obtained. The subjects were then given a Waterpik and instructed to use the appliances to clean their teeth and brackets to the best of their ability, for 2 minutes. Intraoral photographs were obtained. Subjects then had a 1 week (5-9 day) washout period and were then exposed to the other intervention (bromelain rinse).	Subjects were asked to chew a disclosing tablet, swish, and expectorate. Intraoral photographs were obtained. They then received a vial containing 1 gram of bromelain that was reconstituted with 15ml of pineapple juice at 50 degrees F. Subjects swished the solution in their mouth for 2 minutes and then expectorated. Intraoral photographs were obtained. Subjects then received a toothbrush and were asked to brush their teeth for 2 minutes. Intraoral photographs were obtained. The subjects were then given a Waterpik and instructed to use the appliances to clean their teeth and brackets to the best of their ability, for 2 minutes. Intraoral photographs were obtained. Subjects then had a 1 week (5-9 day) washout period and were then exposed to the other intervention (placebo rinse).	Total of all reporting groups
Overall Participants	24	21	45
Age (Count of Participants)
<=18 years	19 79.2%	16 76.2%	35 77.8%
Between 18 and 65 years	5 20.8%	5 23.8%	10 22.2%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	13 54.2%	12 57.1%	25 55.6%
Male	11 45.8%	9 42.9%	20 44.4%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%

Outcome Measures

1. Primary Outcome

Title	Composite Plaque Score
Description	The composite plaque score refers to the cumulative plaque score of all twelve teeth following the administration of the bromelain and placebo (powdered sugar) solutions. The composite plaque score scale had a minimum value of 0 and a maximum value of 48. A score of 0 indicated no plaque was observed on the teeth, while a a score of 48 indicated severe plaque on all possible tooth surfaces. A lower plaque score reflects a better outcome, while a higher plaque score a worse outcome.
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bromelain	Placebo
Arm/Group Description	Subjects were asked to chew a disclosing tablet, swish, and expectorate. Intraoral photographs were obtained. They then received a vial containing 1 gram of bromelain that was reconstituted with 15ml of pineapple juice at 50 degrees F. Subjects swished the solution in their mouth for 2 minutes and then expectorated. Intraoral photographs were obtained. Subjects then received a toothbrush and were asked to brush their teeth for 2 minutes. Intraoral photographs were obtained. The subjects were then given a Waterpik and instructed to use the appliances to clean their teeth and brackets to the best of their ability, for 2 minutes. Intraoral photographs were obtained. Bromelain: The subjects were randomized to either receive the bromelain pre-rinse or the powdered sugar placebo pre-rinse. Subjects then had a 5-9 day washout period and was then exposed to the other intervention.	Subjects were asked to chew a disclosing tablet, swish, and expectorate. Intraoral photographs were obtained. They then received a vial containing 1 gram of powdered sugar that was reconstituted with 15ml of pineapple juice at 50 degrees F. Subjects swished the solution in their mouth for 2 minutes and then expectorated. Intraoral photographs were obtained. Subjects then received a toothbrush and were asked to brush their teeth for 2 minutes. Intraoral photographs were obtained. The subjects were then given a Waterpik and instructed to use the appliances to clean their teeth and brackets to the best of their ability, for 2 minutes. Intraoral photographs were obtained. Powdered sugar: The subjects were randomized to either receive the bromelain pre-rinse or the powdered sugar placebo pre-rinse. Subjects then had a 5-9 day washout period and was then exposed to the other intervention.
Measure Participants	43	43
Mean (Standard Deviation) [score on a scale]	36.2 (10.7)	37.9 (10.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bromelain, Placebo
	Comments	A power analysis determined that a sample size of forty-five (45) subjects would possess 90% power to detect an effect size of 0.5 between the intervention and control legs of the crossover design. With 43 total subjects the study had between 85 and 90% power.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.044
	Comments
	Method	ANOVA
	Comments

Adverse Events

Time Frame	7 days
Arm/Group Title	Bromelain		Placebo
Arm/Group Description	Subjects were asked to chew a disclosing tablet, swish, and expectorate. Intraoral photographs were obtained. They then received a vial containing 1 gram of bromelain that was reconstituted with 15ml of pineapple juice at 50 degrees F. Subjects swished the solution in their mouth for 2 minutes and then expectorated. Intraoral photographs were obtained. Subjects then received a toothbrush and were asked to brush their teeth for 2 minutes. Intraoral photographs were obtained. The subjects were then given a Waterpik and instructed to use the appliances to clean their teeth and brackets to the best of their ability, for 2 minutes. Intraoral photographs were obtained. Bromelain: The subjects were randomized to either receive the bromelain pre-rinse or the powdered sugar placebo pre-rinse. Subjects then had a 5-9 day washout period and was then exposed to the other intervention.		Subjects were asked to chew a disclosing tablet, swish, and expectorate. Intraoral photographs were obtained. They then received a vial containing 1 gram of powdered sugar that was reconstituted with 15ml of pineapple juice at 50 degrees F. Subjects swished the solution in their mouth for 2 minutes and then expectorated. Intraoral photographs were obtained. Subjects then received a toothbrush and were asked to brush their teeth for 2 minutes. Intraoral photographs were obtained. The subjects were then given a Waterpik and instructed to use the appliances to clean their teeth and brackets to the best of their ability, for 2 minutes. Intraoral photographs were obtained. Powdered sugar: The subjects were randomized to either receive the bromelain pre-rinse or the powdered sugar placebo pre-rinse. Subjects then had a 5-9 day washout period and was then exposed to the other intervention.
All Cause Mortality
	Bromelain		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/43 (0%)		0/43 (0%)
Serious Adverse Events
	Bromelain		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/43 (0%)		0/43 (0%)
Other (Not Including Serious) Adverse Events
	Bromelain		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/43 (0%)		0/43 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.