UMIN-CTR Clinical Trial

Public title

Clinical trials of toothpaste gel containing propolis

Acronym

Propolis toothpaste test

Scientific Title

Clinical Trial of Medicated Dentopolis EX Toothpaste Gel

Scientific Title:Acronym

Medicated Dentopolis EX toothpaste test

Region

Japan

Condition

Periodontal disease

Classification by specialty

Dental medicine

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

The aim is to demonstrate the efficacy of propolis extract in improving the oral environment.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

To assess the efficacy of toothbrushing with propolis-containing toothpaste gel on the gingival index and plaque index after one and two weeks.

Key secondary outcomes

To assess the efficacy of toothbrushing with propolis-containing toothpaste gel on the bacterial flora in the tongue after one and two weeks.

Study type

Interventional

Basic design

Cross-over

Randomization

Randomized

Randomization unit

Individual

Blinding

Double blind -all involved are blinded

Control

Placebo

Stratification

NO

Dynamic allocation

YES

Institution consideration

Institution is not considered as adjustment factor.

Blocking

YES

Concealment

No need to know

No. of arms

2

Purpose of intervention

Prevention

Type of intervention

Other

Interventions/Control_1

Intervention 1: Toothpaste A (test toothpaste) => (washout period: 1 month) => Toothpaste B (placebo toothpaste)
Test toothpaste: Toothpaste containing 0.05 w/w% isopropyl methylphenol, 0.1 w/w% tocopherol acetate, and 0.0347 w/v% propolis extract in toothpaste.
Placebo toothpaste: The placebo toothpaste was prepared by removal of the propolis extract from the test toothpaste.
Time of observation: Three times at baseline, one week and two weeks after the start of use of the test toothpaste and three times at baseline, one week and two weeks after the start of use of the placebo toothpaste, for a total of six observations.
Method of toothpaste use
1, Twice a day (morning and before bedtime), brush for 6 minutes (1 minute for each block) using a suitable amount (approx. 0.5 g) of toothpaste per toothpaste using the bath method. After brushing, rinse the mouth with water for 20 seconds.
2, Brushing method: Each participant brushes as usual.
3, Toothbrush used: Dent EX34 Slim Head II

Interventions/Control_2

Intervention 2: Toothpaste B (placebo toothpaste) => (washout period: 1 month) => Toothpaste A (test toothpaste)
Test toothpaste: Toothpaste containing 0.05 w/w% isopropyl methylphenol, 0.1 w/w% tocopherol acetate, and 0.0347 w/v% propolis extract in toothpaste.
Placebo toothpaste: The placebo toothpaste was prepared by removal of the propolis extract from the test toothpaste.
Time of observation: Three times at baseline, one week and two weeks after the start of use of the placebo toothpaste and three times at baseline, one week and two weeks after the start of use of the test toothpaste, for a total of six observations.
Method of toothpaste use
1, Twice a day (morning and before bedtime), brush for 6 minutes (1 minute for each block) using a suitable amount (approx. 0.5 g) of toothpaste per toothpaste using the bath method. After brushing, rinse the mouth with water for 20 seconds.
2, Brushing method: Each participant brushes as usual.
3, Toothbrush used: Dent EX34 Slim Head II

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

18

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Adults (students) with gingivitis or periodontitis

Key exclusion criteria

1. Participants deemed unsuitable for the study by the dentist on the basis of an oral examination at the start of the study due to severe oral disease, perioral injury, etc.
2. Participants who have taken or are taking any medication (e.g. antibiotics) between one month before the start of the study and the end of the study that may affect the results of the study.
3. Participants who have prostheses, defects, etc. on the tooth being studied or its replacement that make them unsuitable for evaluation.
4. Any other participant whom the dentist considers unsuitable for any reasonable reason.

Target sample size

48

Name of lead principal investigator

1st name	Shigeru
Middle name
Last name	Amano

Organization

Meikai University School of Dentistry

Division name

Meikai University Research Institute of Odontology

Zip code

350-0283

Address

1-1, Keyakidai, Sakado city, Saitama, Japan

TEL

049-279-2787

Email

shigerua@dent.meikai.ac.jp

Name of contact person

1st name	Shigeru
Middle name
Last name	Amano

Organization

Meikai University School of Dentistry

Division name

Meikai University Research Institute of Odontology

Zip code

350-0283

Address

1-1, Keyakidai, Sakado city, Saitama, Japan

TEL

049-279-2787

Homepage URL

Email

shigerua@dent.meikai.ac.jp

Institute

Meikai University

Institute

Department

Personal name

Organization

Ohki Pharmaceutical Co., Ltd.,

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Meikai University School of Dentistry

Address

1-1, Keyakidai, Sakado city, Saitama, Japan

Tel

049-279-2712

Email

kenkyu@dent.meikai.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2024

Year

07

Month

29

Day

URL releasing protocol

http://www.kokuhoken.jp/jaob59/

Publication of results

Partially published

URL related to results and publications

http://www.kokuhoken.jp/jaob59/

Number of participants that the trial has enrolled

45

Results

PI and GI scores were significantly (p<0.05) reduced up to 2 weeks with the use of toothpaste containing BGP; GI-regression (r) and PI-r were statistically (p<0.05) significantly reduced, but not GI-r, with the use of toothpaste containing BGP. P. gingivalis and F. nucleatum were statistically (p<0.05) significantly reduced by the use of BGP toothpaste, as was the percentage of periodontal bacteria on the tongue surface. However, A. actinomycetemcomitans and S. salivarius remained unchanged.

Results date posted

2024

Year

07

Month

29

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Adults (participants) with gingivitis or periodontitis. Participants were randomly selected and equally allocated to two groups in sequence: propolis and placebo. Overall, 48 university student volunteers, aged 18-41 years (24 females and 24 males), from the Meikai University School of Dentistry were categorized into groups A (n=24) and B (n=24).

Participant flow

Group A
1, Enrollment
Assessed for eligibility (n=48)
Excluded (n= 0)
Did not meet inclusion criteria (n=0), Declined to participate (n=0), Other reason (n=0)
Randomized (n= 48 )
2, Allocation
Allocated to study group A (toothpaste with propolis) (n=24)
Received allocated intervention (n= 24), Did not receive allocated intervention (n=0)
3, Follow up
Lost to follow-up (n=0)
Did not keep appointment (n= 0 ), Had protocol deviation (n=0)
4, Analysis
Analyzed (n=24)
Excluded from analysis (n=0)
5, 31 days washout phase (each university student used their own toothpaste.)
6, Allocation
Allocated to study group A (toothpaste without propolis) (placebo) (n=24)
Received allocated intervention (n=24), Did not receive allocated intervention (n=0)
7, Follow up
Lost to follow-up (n=2)
Did not keep appointment (n=2), Had protocol deviation (n=0)
8, Analysis
Analyzed (n=22)
Excluded from analysis (n=0)

Group B
1, Enrollment
Assessed for eligibility (n=48)
Excluded (n= 0)
Did not meet inclusion criteria (n=0), Declined to participate (n=0), Other reason (n=0)
Randomized (n= 48)
2, Allocation
Allocated to study group B (toothpaste without propolis) (placebo) (n=24)
Received allocated intervention (n=24), Did not receive allocated intervention (n=0)
3, Follow up
Lost to follow-up (n=1)
Did not keep appointment (n=1), Had protocol deviation (n=0)
4, Analysis
Analyzed (n=23)
Excluded from analysis (n=0)
5, 31 days washout phase (each university student used their own toothpaste.)
6, Allocation
Allocated to study group B (toothpaste with propolis) (n=23)
Received allocated intervention (n= 23), Did not receive allocated intervention (n=0 )
7, Follow up
Lost to follow-up (n=0)
Did not keep appointment (n= 0), Had protocol deviation (n=0)
8, Analysis
Analyzed (n=23)
Excluded from analysis (n=0)

Adverse events

No adverse events were observed.

Outcome measures

1, Plaque Index
Maxillary right sides 2 and 6, left side 4, mandibular left sides 2 and 6, right side 4 are used. A total of 24 proximal, distal, buccal and lingual planes of each tooth should be observed. However, if the target tooth cannot be assessed due to a prosthesis or defect, or if the target tooth is not inflamed but the modified tooth is inflamed, 2 uses 3, 4 uses 5 and 6 uses 7. The plaque index for an individual is expressed as the sum of the split-tooth plaque index for each tooth divided by the number of tooth surfaces examined.
Judgment criteria
0=No plaque. Run the deep needle over the tooth surface and no plaque adheres to the tip of the deep needle.
1=Film-like plaque adherence. Plaque adhesion at the gingival margin not visible to the naked eye, but seen with a deep needle.
2=Thin to moderately thick plaque covering. Plaque is visible to the naked eye in pockets or at the gingival margin.
3=Presence of a high degree of plaque. Accumulation with a thickness (1-2 mm) that extends beyond the concavity created by the gingival margin and tooth surface.

2, Gingival Index
Maxillary right side 2 and 6, left side 4; mandibular left side 2 and 6, right side 4. A total of 24 gingival sites on the proximal, distal, buccal and lingual sides of each tooth should be observed. However, if the target tooth cannot be assessed due to a prosthesis or defect, or if the target tooth is not inflamed but the modified tooth is inflamed, 3 is used for 2, 5 for 4 and 7 for 6. The individual gingival index is expressed as the sum of the split-tooth surface gingivitis index for each tooth divided by the number of subject tooth surfaces.
Judgment criteria
0=Normal gingiva
1=Slight inflammation, slight color change, edema, but no bleeding by probe
2=Moderate inflammation, erythema, edema, and bleeding on probing
3=Severe inflammation, marked erythema, swelling, tendency to spontaneous bleeding, and ulceration

3, Measurement of the number of bacteria in the tongue
A standard curve was constructed from the number of bacteria diluted to 1/10 and the Ct value obtained by quantitative PCR, and quantitative PCR was performed using 10 ng of DNA extracted from the participants' tongues to calculate the number of bacteria.
Bacteria examined.
Fusobacterium nucleatum, Prevotella intermedia, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Streptococcus salivarius, All bacteria
Primer set
Aggregatibacter actinomycetemcomitans Forward Primer-- cttacctactcttgacatccgaa
Aggregatibacter actinomycetemcomitans Reverse Primer-- atgcagcacctgtctctcaaagc
Fusobacterium nucleatum Forward Primer --------------- tgtagttccgcttacctctccag
Fusobacterium nucleatum Reverse Primer---------------- aagcgcgtctctaggtggttatgt
Porphyromonas gingivalis Forward Primer -------------- cttgacttcagtggcggcag
Porphyromonas gingivalis Reverse Primer--------------- agggaagacggttttttcaaca
Prevotella intermedia Forward Primer ----------------- aatacccgatgttgtccaca
Prevotella intermedia Reverse Primer------------------ ttagccggtccttattcgaa
Streptococcus salivarius Forward Primer -------------- ctgtcaaagaagccactggttcaactactg
Streptococcus salivarius Reverse Primer -------------- gattcaatcactacaccagcttcagaggc
Streptococcus salivarius (probe) (FAM-gattctgaaattgctgtcgtcg-TAMRA)
All-bacteria Forward Primer -------------------------- gtgStgcaYggYtgtcgtca
All-bacteria Reverse Primer -------------------------- acgtcRtccMcaccttcctc
S: c or t, Y: c or g, R: a or g, M: a or c

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2014

Year

10

Month

01

Day

Date of IRB

2015

Year

01

Month

22

Day

Anticipated trial start date

2014

Year

10

Month

01

Day

Last follow-up date

2015

Year

09

Month

11

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2024

Year

07

Month

29

Day

Last modified on

2024

Year

07

Month

29

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000062949