Effects of Probiotics on Oral Health

• Sponsor: Kuwait University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02444182
• Collaborator: University of Turku (Other)
• Enrollment: 108
• Location: 1
• Arms: 2
• Duration (Months): 6
• Patients Per Site Per Month: 18.1

Study Details

Study Description

Brief Summary

Some probiotics have been shown to have preventive effects on infectious diseases and allergies. Because their long-term enhancement of the immune responses of children, they have been recommended for infants in some countries. The most promising ones seem to be the combination of Bifidobacterium lactis BB-12 and Lactobacillus rhamnosus GG. Probiotic microbes are mainly ingested orally and the gastrointestinal tract is thus the primary target organ for them. However, the mouth is the first part of the gastrointestinal tract. Most probiotics are in theory cariogenic, thus their effects on oral health should be known. Several probiotics decrease levels of salivary mutans streptococci (MS), but in other respects very little is known about their effects on the oral microbiota. Also effects of probiotics on dental plaque should be studied. This study aims to find out the effects of the combination of BB-12 and LGG, delivered with a lozenge (4 weeks, twice a day) with a mixture of them on the amount of plaque and gingival health

Condition or Disease	Intervention/Treatment	Phase
Periodontal Health; Dental Plaque Accumulation	Dietary Supplement: Probiotics; Dietary Supplement: Placebo	Phase 1/Phase 2

Detailed Description

The Food and Agriculture Organization (FAO) of the United Nations and the World Health Organization (WHO) have defined probiotics as "live micro-organisms, which when administered in adequate amounts, confer a health benefit to the host" (WHO 2002). They should preferably be of human origin, be able to temporarily colonize the gastrointestinal tract and survive in it. They must also be non-pathogenic and non-toxic.

Probiotics are used in the prevention and treatment of infectious diseases and allergies (Hatakka and Saxelin, 2008; Salminen et al., 2010). In some countries probiotics are recommended for infants and adults because of their long-term enhancement of the immune responses. Combinations of probiotics, like Bifidobacterium lactis BB-12 (BB-12) and Lactobacillus rhamnosus GG (LGG), appear to be most effective in this respect (Isolauri et al., 2000; Rautava et al., 2009; Smith et al., 2012). Probiotics are mainly ingested orally, and the gastrointestinal tract is thus the primary target organ for probiotic micro-organisms. However, when ingested in the form of for example tablets, chewing gums, cheese and milk, the oral cavity is exposed to the probiotics. With the world-wide increase in the use of probiotics their effects of on oral health have become a hot topic.

Many types of probiotic bacteria have been explored but the most widely studied species are those that belong to the genera Lactobacillus and Bifidobacterium. Yogurt and fermented milk products are considered the simplest source of probiotic administration for humans. The proven effects of probiotics in general health has led to more research in the oral health field including dental caries, periodontal disease and halitosis. Some clinical studies have demonstrated a decrease in the cariogenic mutans streptococci counts and in dental plaque (Näse et al. 2001, Ahola et al. 2002, Nikawa et al. 2004, Caglar et al. 2007, Twetman & Keller 2012). Probiotics have also shown improvements in the periodontal status in patients with periodontal disease (Riccia et al. 2007, Shimauchi et al. 2008, Teughels et al. 2013, Yanine et al. 2013). Recently, Toiviainen et al. (2015) found that the combination of Lactobacillus rhamnosus GG (LGG) and Bifidobacterium strain Bifidobacterium lactis (BB-12) improved the periodontal health in healthy adults by reducing the plaque amount and subsequently the gingival inflammation without affecting the oral microbiota.

More evidence is necessary to confirm the efficacy of the combination of LGG and BB-12 in the oral health.

Study Design

• Study Type: Interventional
• Actual Enrollment: 108 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Effect of Lactobacillus Rhamnosus LGG and Bifidobacterium Lactis BB-12 on Gingival Health and Dental Plaque in Healthy Adolescents: a Randomized Controlled Clinical Trial
• Study Start Date: Dec 1, 2014
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Probiotics participants will receive a lozenge containing mixture of probiotic bacteria BB-12 and LGG	Dietary Supplement: Probiotics; A half of the participants will be randomly allocated to the probiotics group. They will receive a probiotics lozenge twice a day for 4 weeks. Pre and Post intervention clinical exam will be conducted
Placebo Comparator: Control - No probiotics Participants will receive a control lozenge containing no probiotics. all lozenges are sugar-free; sweetened by xylitol (0.5 g xylitol per piece)	Dietary Supplement: Placebo; A half of the participants will be randomly allocated to the placebo group. Lozenges with no probiotics will be given twice daily for 4 weeks. Pre and Post intervention clinical exam will be conducted

Outcome Measures

Primary Outcome Measures

1. Gingival Health [Four weeks]

   The gingival Index of Loe and Silness (1963) was used to record all surfaces (buccal, lingual, mesial, distal) for index teeth (16, 12, 24, 36, 32, 44). Gingival pockets were gently touched with a periodontal probe and possible bleeding was registered. The criteria are: 0 = no inflammation = mild inflammation, slight change in color, slight edema, no bleeding on probing = moderate inflammation, moderate glazing, redness, bleeding on probing = severe inflammation, marked redness and hypertrophy, ulceration, tendency to spontaneous bleeding The GI of the tooth was determined by adding the scores of the four surfaces and divided the total by four. The GI of the individual was obtained by adding the values of each tooth and dividing by the number of teeth examined A score from 0.1-1.0 = mild inflammation; 1.1-2.0 = moderate inflammation, and 2.1-3.0 = severe inflammation

2. Plaque Index [four weeks]

   A modified Quickley-Hein plaque index (PI) was used to record the buccal and lingual surfaces of all teeth (from right second molar to left second molar) 0 = no plaque = separate flecks of plaque at the cervical margin of the tooth = a thin continuous band of plaque at the cervical margin = a band of plaque wider than 1 mm but covering less than 1/3 of the crown = plaque covering at least 1/3 but less than 2/3 of the crown = plaque covering 2/3 or more of crown An index for the entire mouth is determined by dividing the total score by the number surfaces (a maximum of 2 x 2 x 14 = 56 surfaces) examined. ** Plaque index score reported in the table below represents Pl for the entire mouth. the range is between 0 (no plaque) to 5 (maximum plaque coverage)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 13 Years to 15 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy Adolescent - ASA I & II

• No Antibiotics use

• No intake of commercially available probiotics products during the intervention

Exclusion Criteria:

• Adolescents have ASA III or IV

• Antibiotics use

• refuse to stop taking commercially available probiotics products during intervention

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Abdullah Alwaheeb intermediate School	Kuwait		Kuwait	13110

Sponsors and Collaborators

• Kuwait University
• University of Turku

Investigators

• Principal Investigator: ABRAR N ALANZI, MS, KUWAIT UNIVERISTY

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: ABRAR ALANZI, ASSISTANT PROFESSOR, Kuwait University
• ClinicalTrials.gov Identifier: NCT02444182
• Other Study ID Numbers: DD04/13
• First Posted: May 14, 2015
• Last Update Posted: Mar 14, 2016
• Last Verified: Feb 1, 2016

• Additional relevant MeSH terms: Dental Plaque

Study Results

Participant Flow

Pre-assignment Detail	Inclusion criteria of the study: healthy subject with no history of systemic antibiotics or topical fluoride treatments within the 4 weeks prior to baseline subject who agrees to suck lozenges containing probiotics twice a day. subject who agrees to stop taking any other probiotic containing products during the study period

Arm/Group Title	Probiotics	Control - No Probiotics
Arm/Group Description	participants received a lozenge containing mixture of probiotic bacteria BB-12 and LGG Probiotics: A half of the participants was randomly allocated to the probiotics group. They received probiotics lozenges twice a day for 4 weeks. Pre and Post intervention clinical exams were conducted	Participants received a control lozenge containing no probiotics. all lozenges were sugar-free; sweetened by xylitol (0.5 g xylitol per piece) Placebo: A half of the participants was randomly allocated to the placebo group. Lozenges with no probiotics were given twice daily for 4 weeks. Pre and Post intervention clinical exams were conducted
Period Title: Overall Study
STARTED	54	54
COMPLETED	52	49
NOT COMPLETED	2	5

Baseline Characteristics

Arm/Group Title	Probiotics	Control - No Probiotics	Total
Arm/Group Description	participants received a lozenge containing mixture of probiotic bacteria BB-12 and LGG Probiotics: A half of the participants was randomly allocated to the probiotics group. They received probiotics lozenges twice a day for 4 weeks. Pre and Post intervention clinical exams were conducted	Participants received a control lozenge containing no probiotics. all lozenges were sugar-free; sweetened by xylitol (0.5 g xylitol per piece) Placebo: A half of the participants was randomly allocated to the placebo group. Lozenges with no probiotics were given twice daily for 4 weeks. Pre and Post intervention clinical exams were conducted	Total of all reporting groups
Overall Participants	54	54	108
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14 (1)	14 (1)	14 (1)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	54 100%	54 100%	108 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	54 100%	54 100%	108 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Kuwait	54 100%	54 100%	108 100%

Outcome Measures

1. Primary Outcome

Title	Gingival Health
Description	The gingival Index of Loe and Silness (1963) was used to record all surfaces (buccal, lingual, mesial, distal) for index teeth (16, 12, 24, 36, 32, 44). Gingival pockets were gently touched with a periodontal probe and possible bleeding was registered. The criteria are: 0 = no inflammation = mild inflammation, slight change in color, slight edema, no bleeding on probing = moderate inflammation, moderate glazing, redness, bleeding on probing = severe inflammation, marked redness and hypertrophy, ulceration, tendency to spontaneous bleeding The GI of the tooth was determined by adding the scores of the four surfaces and divided the total by four. The GI of the individual was obtained by adding the values of each tooth and dividing by the number of teeth examined A score from 0.1-1.0 = mild inflammation; 1.1-2.0 = moderate inflammation, and 2.1-3.0 = severe inflammation
Time Frame	Four weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Probiotics	Control - No Probiotics
Arm/Group Description	participants received a lozenge containing mixture of probiotic bacteria BB-12 and LGG Probiotics: A half of the participants was randomly allocated to the probiotics group. They received probiotics lozenges twice a day for 4 weeks. Pre and Post intervention clinical exams were conducted	Participants received a control lozenge containing no probiotics. all lozenges were sugar-free; sweetened by xylitol (0.5 g xylitol per piece) Placebo: A half of the participants was randomly allocated to the placebo group. Lozenges with no probiotics were given twice daily for 4 weeks. Pre and Post intervention clinical exams were conducted
Measure Participants	52	49
Mean (Standard Deviation) [units on a scale]	0.46 (0.6)	0.18 (0.39)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Probiotics, Control - No Probiotics
	Comments	Null hypothesis was no difference in Gingival index between probiotics and control groups
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.015
	Comments
	Method	paired t-test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.28
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 0.21
	Estimation Comments

2. Primary Outcome

Title	Plaque Index
Description	A modified Quickley-Hein plaque index (PI) was used to record the buccal and lingual surfaces of all teeth (from right second molar to left second molar) 0 = no plaque = separate flecks of plaque at the cervical margin of the tooth = a thin continuous band of plaque at the cervical margin = a band of plaque wider than 1 mm but covering less than 1/3 of the crown = plaque covering at least 1/3 but less than 2/3 of the crown = plaque covering 2/3 or more of crown An index for the entire mouth is determined by dividing the total score by the number surfaces (a maximum of 2 x 2 x 14 = 56 surfaces) examined. ** Plaque index score reported in the table below represents Pl for the entire mouth. the range is between 0 (no plaque) to 5 (maximum plaque coverage)
Time Frame	four weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Probiotics	Control - No Probiotics
Arm/Group Description	participants received a lozenge containing mixture of probiotic bacteria BB-12 and LGG Probiotics: A half of the participants was randomly allocated to the probiotics group. They received probiotics lozenges twice a day for 4 weeks. Pre and Post intervention clinical exams were conducted	Participants received a control lozenge containing no probiotics. all lozenges were sugar-free; sweetened by xylitol (0.5 g xylitol per piece) Placebo: A half of the participants was randomly allocated to the placebo group. Lozenges with no probiotics were given twice daily for 4 weeks. Pre and Post intervention clinical exams were conducted
Measure Participants	52	49
Mean (Standard Deviation) [units on a scale]	0.80 (0.76)	0.71 (0.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Probiotics, Control - No Probiotics
	Comments	Null hypothesis was no difference in plaque index between probiotics and control groups
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.909
	Comments
	Method	paired t-test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.09
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 0.09
	Estimation Comments

Adverse Events

Time Frame	4 weeks
Arm/Group Title	Probiotics		Control - No Probiotics
Arm/Group Description	participants received a lozenge containing mixture of probiotic bacteria BB-12 and LGG Probiotics: A half of the participants was randomly allocated to the probiotics group. They received probiotics lozenges twice a day for 4 weeks. Pre and Post intervention clinical exams were conducted		Participants received a control lozenge containing no probiotics. all lozenges were sugar-free; sweetened by xylitol (0.5 g xylitol per piece) Placebo: A half of the participants was randomly allocated to the placebo group. Lozenges with no probiotics were given twice daily for 4 weeks. Pre and Post intervention clinical exams were conducted
All Cause Mortality
	Probiotics		Control - No Probiotics
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Probiotics		Control - No Probiotics
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/54 (0%)		0/54 (0%)
Other (Not Including Serious) Adverse Events
	Probiotics		Control - No Probiotics
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/54 (0%)		0/54 (0%)

Limitations/Caveats

limitations of this study include: short period: only 4 weeks to reach maximum compliance number of participants: just above the minimum sample size due to refusal of many parents to give consent for their children participation.

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.