UMIN-CTR Clinical Trial

Public title

Study on Clinical Effects of Toothpaste Containing Propolis in Periodontitis Patients

Acronym

Effects of Toothpaste Containing Propolis in Periodontitis Patients

Scientific Title

Study on Clinical Effects of Toothpaste Containing Propolis in Periodontitis Patients

Scientific Title:Acronym

Effects of Toothpaste Containing Propolis in Periodontitis Patients

Region

Japan

Condition

Periodontitis

Classification by specialty

Dental medicine

Adult

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

This clinical study aimed to evaluate the clinical effects of the toothpaste containing propolis by comparison to the tooth paste not counting propolis in randomized controlled trial.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Phase II

Primary outcomes

Amounts of bacteria in sub-gingival dental plaque after 4 weeks
(Total bacteria and Porphyromonas gingivivalis)

Key secondary outcomes

Nine points after 4 weeks
1) Probing pocket depth
2) Bleeding on probing
3) Activity of neutrophil elastase and total protein amounts in saliva
4) Ammonia in saliva
5) Cariogenic activity of saliva: amounts of cariogenic bacteria, acidity, buffer capacity
6) Microflora of sub-gingival dental plaque analyzed by next generation sequencer (2 subjects/group)
7) Questionnaire for impression of use of this toothpaste and its effective
8) Record of implementation
9) Questionnaire for the condition of pre-existing disease

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Double blind -all involved are blinded

Control

Placebo

Stratification

NO

Dynamic allocation

NO

Institution consideration

Institution is not considered as adjustment factor.

Blocking

NO

Concealment

Central registration

No. of arms

2

Purpose of intervention

Prevention

Type of intervention

Other

Interventions/Control_1

Tooth brushing with given toothbrush and toothpaste containing 5 mg/g propolis twice a day for 4 weeks

Interventions/Control_2

Tooth brushing with given toothbrush and toothpaste not containing propolis twice a day for 4 weeks

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1) Periodontitis patients in supportive periodontal therapy (SPT) phase (consulting period: more than 2 months interval) at Department of Periodontics and Endodontics of Okayama University Hospital
2) Good oral hygiene; good compliance during study period, judged by research dentist
3) Age is not less than 20 years old when obtaining informed consent.
4) Current number of teeth is not less than 20.
5) Patients with 3 or more teeth with 4- to 6-mm periodontal pocket
6) Patients with informed consent by document agree

Key exclusion criteria

1) Allergic for this toothpaste
2) Pregnancy or lactating period women
3) Unstable physical condition
4) Use of antibiotics / anti-inflammatory agents within 3 months
5) Acute symptom of periodontitis within 3 months
6) Smoker
7) Unifit patients judged by research dentists for compliance

Target sample size

40

Name of lead principal investigator

1st name
Middle name
Last name	Shogo Takashiba

Organization

Okayama University

Division name

Department of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

Zip code

Address

2-5-1 Shikata-cho, Kita-ku, Okayama 700-8525, Japan

TEL

086-235-6675

Email

stakashi@okayama-u.ac.jp

Name of contact person

1st name
Middle name
Last name	Shogo Takashiba

Organization

Okayama University

Division name

Department of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine,

Zip code

Address

2-5-1 Shikata-cho, Kita-ku, Okayama 700-8525, Japan

TEL

086-235-6675

Homepage URL

Email

stakashi@okayama-u.ac.jp

Institute

Okayama University

Institute

Department

Personal name

Organization

API Co., Ltd.
Business Strategy Section

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

岡山大学病院（岡山市）

Date of disclosure of the study information

2017

Year

10

Month

14

Day

URL releasing protocol

None

Publication of results

Unpublished

URL related to results and publications

None

Number of participants that the trial has enrolled

29

Results

Primary endpoints
Total bacterial count: There was no significant difference between the control and propolis groups before and after the test.
There was no significant difference in the number of Pg bacteria between the control and propolis groups before and after the test.

Results date posted

2021

Year

10

Month

19

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Selection criteria: 1.
1. Selection criteria: Patients who meet the following conditions are eligible.
(1) Patients with periodontitis who have completed treatment for periodontitis at the Department of Periodontology, Okayama University Hospital, and whose condition is stable, and who continue to visit the hospital regularly for SPT (at intervals of 2 months or more).
(2) Patients whose oral hygiene is good and who are judged by the research physician to be able to clean their mouths according to the dentist's instructions during the study period.
(3) Patients who were 20 years of age or older at the time consent was obtained.
(4) Patients who currently have 20 or more teeth.
(5) Patients who still have periodontal pockets of 4-6 mm on at least 3 teeth.
(6) Patients who have obtained written consent from the patient himself/herself after receiving sufficient explanation for participation in this study.
2. Exclusion criteria
2. Exclusion criteria: Patients who violate any of the following criteria will not be included in this study.
(1) Patients who are allergic to toothpaste (if allergic symptoms occur)
(2) Pregnant or lactating women
(3) Patients whose general condition is unstable (those whose physical condition fluctuates greatly)
(4) Patients who have received topical or systemic antibiotics or anti-inflammatory drugs within the past 3 months
(5) Patients with acute symptoms of periodontitis within the past 3 months
(6) Smokers
(7) Others who are judged by the attending physician to be ineligible.

Participant flow

A randomized, double-blind study of the clinical effects of propolis-containing toothpaste on periodontitis compared with placebo toothpaste without propolis in patients in the SPT stage.

Adverse events

None

Outcome measures

Primary endpoint
Amount of bacteria in the subgingival plaque after 4 weeks (quantitative PCR method)
Subgingival plaque was collected by paper point from 3 teeth with 4-6 mm periodontal pockets, and DNA was extracted. The total number of bacteria and the number of Porphyromonas gingivalis (Pg) will be measured by real-time PCR using the extracted DNA sample as a template.
Secondary endpoint
The following 9 items will be measured after 4 weeks
(1) Periodontal pocket depth
The depth of periodontal pockets at three sites where subgingival plaque was collected will be measured by the method used in regular practice.
(2) BOP score
To measure the depth of periodontal pockets at three sites from which subgingival plaque was collected using the usual method, and to check for bleeding.
(3) Leukocyte esterase activity and total protein level in saliva
Measurement by test paper using Lion's test kit (Salivary Multitest: SMT; http://lionpro.lionshop.jp/).
(4) Ammonia in saliva
Ammonia, the cause of bad breath, is detected by bromocresol green coloration using SMT as well.
(5) Amount, acidity, and buffering capacity of caries-producing bacteria in saliva
Similarly, SMT is used to detect the ability of Gram-positive bacteria to reduce resazurin, which has been shown to be related to the number of caries-producing bacteria. In addition, the amount of hydrogen ion is detected from the color change of pH indicator, and the acidity related to the demineralization of tooth enamel is examined. In addition, the neutralizing power of saliva against acid (buffering capacity) is examined.
(6) Bacterial flora in subgingival plaque (NGS method)
DNA will be extracted from subgingival plaque, and metagenomic analysis of the oral bacterial flora will be performed using a next-generation sequencer (NGS). Four patients, two in each group, will be measured, and the measurements will be performed on the patients corresponding to the pre-determined toothpaste numbers.
(7) Questionnaire on the feeling of use and effect of toothpaste
(8) Subjects' diary (brushing status)
(9) Changes in underlying diseases (questionnaire)

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2017

Year

01

Month

29

Day

Date of IRB

2017

Year

01

Month

17

Day

Anticipated trial start date

2017

Year

02

Month

01

Day

Last follow-up date

2017

Year

08

Month

31

Day

Date of closure to data entry

2017

Year

10

Month

31

Day

Date trial data considered complete

2018

Year

03

Month

31

Day

Date analysis concluded

2018

Year

03

Month

31

Day

Other related information

Registered date

2017

Year

10

Month

14

Day

Last modified on

2021

Year

10

Month

19

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000028717