Trial Outcomes & Findings for A Clinical Trial to Evaluate Long-term Efficacy and Safety of Lozenges Containing Lactobacilli Reuteri (Prodentis™) on Gingivitis (NCT NCT01811316)

Last Updated: 2017-12-07

Results Overview

Modified Gingival Index (MGI) (Lobene, Weatherford et al. 1986) was measured on six gingival areas of all scorable teeth, using a scale of 0-4 as follows: Scores Criteria 0 Normal (absence of inflammation) 1. Mild inflammation (slight change of color, little change in texture) of any portion of, but not the entire marginal or papillary gingival unit 2. Mild inflammation of the entire gingival unit 3. Moderate inflammation (moderate glazing, redness, edema and/or hypertrophy) of the marginal or papillary gingival unit 4. Severe inflammation (marked redness and edema/hyper-trophy, spontaneous bleeding or ulceration) of the marginal or papillary gingival unit. Whole mouth MGI scores were calculated by summing all scores and dividing by the number of examined scorable sites.

Recruitment status

COMPLETED

Study phase

Target enrollment

62 participants

Primary outcome timeframe

4, 12 and 24 weeks

Results posted on

2017-12-07

Participant Flow

Participant milestones

Participant milestones
Measure	Probiotics Lozenge (Twice a Day) Subjects take their lozenge twice a day, one lozenge in the morning after brushing and one lozenge in the evening after brushing.	Probiotics Lozenge (Once a Day) Subjects take their lozenge once a day, one lozenge at night after brushing.	Placebo Lozenge (Once a Day) Subjects take their lozenge once a day, one lozenge at night after brushing.
Overall Study STARTED	21	22	19
Overall Study Visit 4 Weeks	19	22	19
Overall Study Visit 12 Weeks	18	22	19
Overall Study COMPLETED	18	22	19
Overall Study NOT COMPLETED	3	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Clinical Trial to Evaluate Long-term Efficacy and Safety of Lozenges Containing Lactobacilli Reuteri (Prodentis™) on Gingivitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Probiotics Lozenge (Twice a Day) n=21 Participants Subjects take their lozenge twice a day, one lozenge in the morning after brushing and one lozenge in the evening after brushing.	Probiotics Lozenge (Once a Day) n=22 Participants Subjects take their lozenge once a day, one lozenge at night after brushing.	Placebo Lozenge (Once a Day) n=19 Participants Subjects take their lozenge once a day, one lozenge at night after brushing.	Total n=62 Participants Total of all reporting groups
Age, Continuous	40 Year STANDARD_DEVIATION 13 • n=5 Participants	44 Year STANDARD_DEVIATION 15 • n=7 Participants	34 Year STANDARD_DEVIATION 11 • n=5 Participants	40 Year STANDARD_DEVIATION 13 • n=4 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	13 Participants n=7 Participants	9 Participants n=5 Participants	32 Participants n=4 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	9 Participants n=7 Participants	10 Participants n=5 Participants	30 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=5 Participants	21 Participants n=7 Participants	19 Participants n=5 Participants	59 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	7 Participants n=7 Participants	4 Participants n=5 Participants	14 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	10 Participants n=4 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants	12 Participants n=7 Participants	10 Participants n=5 Participants	34 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants

PRIMARY outcome

Timeframe: 4, 12 and 24 weeks

Population: One subject was lost to follow up between 4 and 12 weeks.

Outcome measures

Outcome measures
Measure	Probiotics Lozenge (Twice a Day) n=19 Participants Subjects take their lozenge twice a day, one lozenge in the morning after brushing and one lozenge in the evening after brushing.	Probiotics Lozenge (Once a Day) n=22 Participants Subjects take their lozenge once a day, one lozenge at night after brushing.	Placebo Lozenge (Once a Day) n=18 Participants Subjects take their lozenge once a day, one lozenge at night after brushing.
Change From Baseline in Modified Gingival Index (MGI) 4 weeks	-0.07 units on a scale Standard Deviation 0.12	-0.09 units on a scale Standard Deviation 0.12	-0.09 units on a scale Standard Deviation 0.12
Change From Baseline in Modified Gingival Index (MGI) 12 weeks	-0.02 units on a scale Standard Deviation 0.11	-0.02 units on a scale Standard Deviation 0.12	-0.04 units on a scale Standard Deviation 0.11
Change From Baseline in Modified Gingival Index (MGI) 24 weeks	0.00 units on a scale Standard Deviation 0.13	-0.04 units on a scale Standard Deviation 0.13	-0.06 units on a scale Standard Deviation 0.12

PRIMARY outcome

Timeframe: 4, 12 and 24 weeks

Population: One subject was lost to follow up between 4 and 12 weeks.

Bleeding on probing was assessed 30 seconds after probing. A dichotomous scoring system was used at six sites per tooth using one (1) and zero (0) for presence or absence, respectively. BOP (%) is a percentage of sites BOP.

Outcome measures

Outcome measures
Measure	Probiotics Lozenge (Twice a Day) n=19 Participants Subjects take their lozenge twice a day, one lozenge in the morning after brushing and one lozenge in the evening after brushing.	Probiotics Lozenge (Once a Day) n=22 Participants Subjects take their lozenge once a day, one lozenge at night after brushing.	Placebo Lozenge (Once a Day) n=19 Participants Subjects take their lozenge once a day, one lozenge at night after brushing.
Change From Baseline in Bleeding on Probing (BOP) 4 weeks	-10.2 percentage of sites BOP Standard Deviation 13.8	-1.8 percentage of sites BOP Standard Deviation 10.7	-3.0 percentage of sites BOP Standard Deviation 9.2
Change From Baseline in Bleeding on Probing (BOP) 12 weeks	-6.6 percentage of sites BOP Standard Deviation 14.9	0.8 percentage of sites BOP Standard Deviation 13.5	2.9 percentage of sites BOP Standard Deviation 14.5
Change From Baseline in Bleeding on Probing (BOP) 24 weeks	-2.3 percentage of sites BOP Standard Deviation 17.1	5.6 percentage of sites BOP Standard Deviation 17.9	3.5 percentage of sites BOP Standard Deviation 14.1

SECONDARY outcome

Timeframe: 4, 12 and 24 weeks

Population: One subject was lost to follow up between 4 and 12 weeks.

Plaque Index of Turesky Modification of Quigley-Hein (Turesky, Gilmore et al. 1970) (PI) was scored on all natural teeth (except third molars) after disclosing with erythrosine solution. Scores Criteria: 0 No plaque 1. Separate flecks of plaque at the cervical margin of the tooth 2. A thin continuous band of plaque (up to one mm) at the cervical margin of the tooth 3. A band of plaque wider than one mm but covering less than one-third of the crown of the tooth 4. Plaque covering at least one-third but less than two-thirds of the crown of the tooth 5. Plaque covering two-thirds or more of the crown of the tooth

Outcome measures

Outcome measures
Measure	Probiotics Lozenge (Twice a Day) n=19 Participants Subjects take their lozenge twice a day, one lozenge in the morning after brushing and one lozenge in the evening after brushing.	Probiotics Lozenge (Once a Day) n=22 Participants Subjects take their lozenge once a day, one lozenge at night after brushing.	Placebo Lozenge (Once a Day) n=18 Participants Subjects take their lozenge once a day, one lozenge at night after brushing.
Change From Baseline in Plaque Index (PI) 4 weeks	0.08 units on a scale Standard Deviation 0.36	0.06 units on a scale Standard Deviation 0.28	0.08 units on a scale Standard Deviation 0.49
Change From Baseline in Plaque Index (PI) 12 weeks	0.18 units on a scale Standard Deviation 0.35	0.06 units on a scale Standard Deviation 0.4	0.00 units on a scale Standard Deviation 0.54
Change From Baseline in Plaque Index (PI) 24 weeks	0.25 units on a scale Standard Deviation 0.44	0.11 units on a scale Standard Deviation 0.39	0.03 units on a scale Standard Deviation 0.47

SECONDARY outcome

Timeframe: 4, 12 and 24 weeks

Population: One subject was lost to follow up between 4 and 12 weeks.

Periodontal pocket depth (PD) was determined with a periodontal probe at six sites per tooth rounded to the next lower whole mm.

Outcome measures

Outcome measures
Measure	Probiotics Lozenge (Twice a Day) n=19 Participants Subjects take their lozenge twice a day, one lozenge in the morning after brushing and one lozenge in the evening after brushing.	Probiotics Lozenge (Once a Day) n=22 Participants Subjects take their lozenge once a day, one lozenge at night after brushing.	Placebo Lozenge (Once a Day) n=19 Participants Subjects take their lozenge once a day, one lozenge at night after brushing.
Change From Baseline in Probing Depth (PD) 4 weeks	0.01 mm Standard Deviation 0.11	0.00 mm Standard Deviation 0.13	0.02 mm Standard Deviation 0.13
Change From Baseline in Probing Depth (PD) 12 weeks	0.01 mm Standard Deviation 0.12	0.03 mm Standard Deviation 0.12	0.10 mm Standard Deviation 0.15
Change From Baseline in Probing Depth (PD) 24 weeks	0.1 mm Standard Deviation 0.11	0.08 mm Standard Deviation 0.15	0.11 mm Standard Deviation 0.19

OTHER_PRE_SPECIFIED outcome

Timeframe: 15 days, 4, 12 and 24 weeks

Gingival Crevicular Fluid (GCF) samples will be analyzed for inflammatory cytokines/chemokines and matrix metalloproteases using multiplexing ELISA.

Outcome measures

Outcome data not reported

Adverse Events

Probiotics Lozenge (Twice a Day)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Probiotics Lozenge (Once a Day)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Placebo Lozenge (Once a Day)

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Probiotics Lozenge (Twice a Day) n=21 participants at risk Subjects take their lozenge twice a day, one lozenge in the morning after brushing and one lozenge in the evening after brushing.	Probiotics Lozenge (Once a Day) n=22 participants at risk Subjects take their lozenge once a day, one lozenge at night after brushing.	Placebo Lozenge (Once a Day) n=19 participants at risk Subjects take their lozenge once a day, one lozenge at night after brushing.
Respiratory, thoracic and mediastinal disorders Cold	0.00% 0/21 • Adverse Event data were collected at each visit over 24 weeks after randomization.	9.1% 2/22 • Number of events 2 • Adverse Event data were collected at each visit over 24 weeks after randomization.	15.8% 3/19 • Number of events 3 • Adverse Event data were collected at each visit over 24 weeks after randomization.
Gastrointestinal disorders Nausea	4.8% 1/21 • Number of events 1 • Adverse Event data were collected at each visit over 24 weeks after randomization.	0.00% 0/22 • Adverse Event data were collected at each visit over 24 weeks after randomization.	5.3% 1/19 • Number of events 1 • Adverse Event data were collected at each visit over 24 weeks after randomization.
Social circumstances Sore throat	4.8% 1/21 • Number of events 1 • Adverse Event data were collected at each visit over 24 weeks after randomization.	0.00% 0/22 • Adverse Event data were collected at each visit over 24 weeks after randomization.	5.3% 1/19 • Number of events 1 • Adverse Event data were collected at each visit over 24 weeks after randomization.
Immune system disorders Allergic sinustis	0.00% 0/21 • Adverse Event data were collected at each visit over 24 weeks after randomization.	0.00% 0/22 • Adverse Event data were collected at each visit over 24 weeks after randomization.	5.3% 1/19 • Number of events 1 • Adverse Event data were collected at each visit over 24 weeks after randomization.

Additional Information

Akane Takemura

Sunstar Americas, Inc.

Phone: +1-847-794-4276

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 30 days from the time submitted to the sponsor for review. PI shall delay publications for up to 90 days upon receipt of a written request from the sponsor in order to allow the sponsor to register intellectual property rights that are included in the proposed publication.
Publication restrictions are in place

Restriction type: OTHER