Gingivitis
Conditions
Brief summary
The purpose of this study is to evaluate the long-term efficacy and safety of lozenges containing probiotics in reducing gingivitis. The primary purpose of this study is to support claims from U.S. instructions for use (IFU) for GUM® PerioBalance®.
Interventions
OTHERProbiotics
Sponsors
Sunstar Americas
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Willing and able to read, understand and sign an Informed Consent form. * Good general health as evidenced by the medical history. * Between 18 and 65 years of age. * Male or female. * Minimum of 20 teeth, excluding crowns and third molar teeth. * Mean whole mouth Modified Gingival Index of greater-than or equal to 2.0 at baseline. * Willing to abstain from all oral hygiene procedures for 12-18 hours prior to clinical visits. * Willing to abstain from eating and drinking in the morning of visits, only drinking water is allowed. * Willing to abstain from interdental cleaning, chewing gums, oral whitening, mouth rinse and tobacco products for the study duration. * Able to understand and follow study directions. * No known history of allergy to dairy products or their ingredients, relevant to any ingredient in the test products as determined by the dental/medical professional monitoring the study.
Exclusion criteria
* Presence of orthodontic appliances. * Intra-oral soft tissue lesions due to pathology or trauma * Patients with aggressive periodontitis, acute necrotizing ulcerative gingivitis, or gross decay at discretion of PI. * More than two sites with pocket depth \>5mm and concomitant attachment loss of \>2mm. * Pregnant or lactating females or females of child bearing potential not using acceptable methods of birth control (hormonal, barriers or abstinence). * Use of antibiotics within 3 months of enrollment * History of drug use that is associated with gum overgrowth (i.e., Dilantin, nifedipine, etc) * Chronic use of medication such as steroids, NSAIDs (more than 2-3 days/week), anti-coagulant medications, immunosuppressant medications or any other medications that in the opinion of the Investigator would interfere with the evaluation or confound interpretation of the study results. Use of low dose of acetylsalicylic acid (81 mg) is permitted. * Unwilling to sign a confidentiality statement and/or return the test products. * Medical condition which requires pre-medication prior to dental visits/procedures. * Immune compromised individuals (HIV, AIDS, immunosuppressive drug therapy). * Current use of probiotics or probiotic containing food (i.e., yogurt)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Modified Gingival Index (MGI) | 4, 12 and 24 weeks | 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. |
| Change From Baseline in Bleeding on Probing (BOP) | 4, 12 and 24 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Plaque Index (PI) | 4, 12 and 24 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 |
| Change From Baseline in Probing Depth (PD) | 4, 12 and 24 weeks | Periodontal pocket depth (PD) was determined with a periodontal probe at six sites per tooth rounded to the next lower whole mm. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Inflammatory Markers in Gingival Crevicular | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 21 |
| Probiotics Lozenge (Once a Day) Subjects take their lozenge once a day, one lozenge at night after brushing. | 22 |
| Placebo Lozenge (Once a Day) Subjects take their lozenge once a day, one lozenge at night after brushing. | 19 |
| Total | 62 |
Baseline characteristics
| Characteristic | Probiotics Lozenge (Twice a Day) | Probiotics Lozenge (Once a Day) | Placebo Lozenge (Once a Day) | Total |
|---|---|---|---|---|
| Age, Continuous | 40 Year STANDARD_DEVIATION 13 | 44 Year STANDARD_DEVIATION 15 | 34 Year STANDARD_DEVIATION 11 | 40 Year STANDARD_DEVIATION 13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 21 Participants | 19 Participants | 59 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 7 Participants | 4 Participants | 14 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 1 Participants | 4 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 12 Participants | 12 Participants | 10 Participants | 34 Participants |
| Sex: Female, Male Female | 10 Participants | 13 Participants | 9 Participants | 32 Participants |
| Sex: Female, Male Male | 11 Participants | 9 Participants | 10 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 21 | 2 / 22 | 5 / 19 |
| serious Total, serious adverse events | 0 / 21 | 0 / 22 | 0 / 19 |
Outcome results
Primary
Change From Baseline in Bleeding on Probing (BOP)
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.
Time frame: 4, 12 and 24 weeks
Population: One subject was lost to follow up between 4 and 12 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Probiotics Lozenge (Twice a Day) | Change From Baseline in Bleeding on Probing (BOP) | 24 weeks | -2.3 percentage of sites BOP | Standard Deviation 17.1 |
| Probiotics Lozenge (Twice a Day) | Change From Baseline in Bleeding on Probing (BOP) | 12 weeks | -6.6 percentage of sites BOP | Standard Deviation 14.9 |
| Probiotics Lozenge (Twice a Day) | Change From Baseline in Bleeding on Probing (BOP) | 4 weeks | -10.2 percentage of sites BOP | Standard Deviation 13.8 |
| Probiotics Lozenge (Once a Day) | Change From Baseline in Bleeding on Probing (BOP) | 24 weeks | 5.6 percentage of sites BOP | Standard Deviation 17.9 |
| Probiotics Lozenge (Once a Day) | Change From Baseline in Bleeding on Probing (BOP) | 4 weeks | -1.8 percentage of sites BOP | Standard Deviation 10.7 |
| Probiotics Lozenge (Once a Day) | Change From Baseline in Bleeding on Probing (BOP) | 12 weeks | 0.8 percentage of sites BOP | Standard Deviation 13.5 |
| Placebo Lozenge (Once a Day) | Change From Baseline in Bleeding on Probing (BOP) | 12 weeks | 2.9 percentage of sites BOP | Standard Deviation 14.5 |
| Placebo Lozenge (Once a Day) | Change From Baseline in Bleeding on Probing (BOP) | 4 weeks | -3.0 percentage of sites BOP | Standard Deviation 9.2 |
| Placebo Lozenge (Once a Day) | Change From Baseline in Bleeding on Probing (BOP) | 24 weeks | 3.5 percentage of sites BOP | Standard Deviation 14.1 |
Primary
Change From Baseline in Modified Gingival Index (MGI)
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.
Time frame: 4, 12 and 24 weeks
Population: One subject was lost to follow up between 4 and 12 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Probiotics Lozenge (Twice a Day) | Change From Baseline in Modified Gingival Index (MGI) | 12 weeks | -0.02 units on a scale | Standard Deviation 0.11 |
| Probiotics Lozenge (Twice a Day) | Change From Baseline in Modified Gingival Index (MGI) | 4 weeks | -0.07 units on a scale | Standard Deviation 0.12 |
| Probiotics Lozenge (Twice a Day) | Change From Baseline in Modified Gingival Index (MGI) | 24 weeks | 0.00 units on a scale | Standard Deviation 0.13 |
| Probiotics Lozenge (Once a Day) | Change From Baseline in Modified Gingival Index (MGI) | 12 weeks | -0.02 units on a scale | Standard Deviation 0.12 |
| Probiotics Lozenge (Once a Day) | Change From Baseline in Modified Gingival Index (MGI) | 4 weeks | -0.09 units on a scale | Standard Deviation 0.12 |
| Probiotics Lozenge (Once a Day) | Change From Baseline in Modified Gingival Index (MGI) | 24 weeks | -0.04 units on a scale | Standard Deviation 0.13 |
| Placebo Lozenge (Once a Day) | Change From Baseline in Modified Gingival Index (MGI) | 4 weeks | -0.09 units on a scale | Standard Deviation 0.12 |
| Placebo Lozenge (Once a Day) | Change From Baseline in Modified Gingival Index (MGI) | 24 weeks | -0.06 units on a scale | Standard Deviation 0.12 |
| Placebo Lozenge (Once a Day) | Change From Baseline in Modified Gingival Index (MGI) | 12 weeks | -0.04 units on a scale | Standard Deviation 0.11 |
Secondary
Change From Baseline in Plaque Index (PI)
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
Time frame: 4, 12 and 24 weeks
Population: One subject was lost to follow up between 4 and 12 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Probiotics Lozenge (Twice a Day) | Change From Baseline in Plaque Index (PI) | 12 weeks | 0.18 units on a scale | Standard Deviation 0.35 |
| Probiotics Lozenge (Twice a Day) | Change From Baseline in Plaque Index (PI) | 4 weeks | 0.08 units on a scale | Standard Deviation 0.36 |
| Probiotics Lozenge (Twice a Day) | Change From Baseline in Plaque Index (PI) | 24 weeks | 0.25 units on a scale | Standard Deviation 0.44 |
| Probiotics Lozenge (Once a Day) | Change From Baseline in Plaque Index (PI) | 12 weeks | 0.06 units on a scale | Standard Deviation 0.4 |
| Probiotics Lozenge (Once a Day) | Change From Baseline in Plaque Index (PI) | 4 weeks | 0.06 units on a scale | Standard Deviation 0.28 |
| Probiotics Lozenge (Once a Day) | Change From Baseline in Plaque Index (PI) | 24 weeks | 0.11 units on a scale | Standard Deviation 0.39 |
| Placebo Lozenge (Once a Day) | Change From Baseline in Plaque Index (PI) | 4 weeks | 0.08 units on a scale | Standard Deviation 0.49 |
| Placebo Lozenge (Once a Day) | Change From Baseline in Plaque Index (PI) | 24 weeks | 0.03 units on a scale | Standard Deviation 0.47 |
| Placebo Lozenge (Once a Day) | Change From Baseline in Plaque Index (PI) | 12 weeks | 0.00 units on a scale | Standard Deviation 0.54 |
Secondary
Change From Baseline in Probing Depth (PD)
Periodontal pocket depth (PD) was determined with a periodontal probe at six sites per tooth rounded to the next lower whole mm.
Time frame: 4, 12 and 24 weeks
Population: One subject was lost to follow up between 4 and 12 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Probiotics Lozenge (Twice a Day) | Change From Baseline in Probing Depth (PD) | 4 weeks | 0.01 mm | Standard Deviation 0.11 |
| Probiotics Lozenge (Twice a Day) | Change From Baseline in Probing Depth (PD) | 12 weeks | 0.01 mm | Standard Deviation 0.12 |
| Probiotics Lozenge (Twice a Day) | Change From Baseline in Probing Depth (PD) | 24 weeks | 0.1 mm | Standard Deviation 0.11 |
| Probiotics Lozenge (Once a Day) | Change From Baseline in Probing Depth (PD) | 12 weeks | 0.03 mm | Standard Deviation 0.12 |
| Probiotics Lozenge (Once a Day) | Change From Baseline in Probing Depth (PD) | 4 weeks | 0.00 mm | Standard Deviation 0.13 |
| Probiotics Lozenge (Once a Day) | Change From Baseline in Probing Depth (PD) | 24 weeks | 0.08 mm | Standard Deviation 0.15 |
| Placebo Lozenge (Once a Day) | Change From Baseline in Probing Depth (PD) | 4 weeks | 0.02 mm | Standard Deviation 0.13 |
| Placebo Lozenge (Once a Day) | Change From Baseline in Probing Depth (PD) | 24 weeks | 0.11 mm | Standard Deviation 0.19 |
| Placebo Lozenge (Once a Day) | Change From Baseline in Probing Depth (PD) | 12 weeks | 0.10 mm | Standard Deviation 0.15 |
Other Pre-specified
Change From Baseline in Inflammatory Markers in Gingival Crevicular
Gingival Crevicular Fluid (GCF) samples will be analyzed for inflammatory cytokines/chemokines and matrix metalloproteases using multiplexing ELISA.
Time frame: 15 days, 4, 12 and 24 weeks