Effects on Tablets Containing Probiotic Candidate Strains on Clinical and Cytokine Markers of Gingival Inflammation and Composition of the Salivary Microbiome
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Cytokines in GCF: INFγ, TNF-α, IL-8, IL-10 and IL-12 (ng/uL)
研究概览
简要总结
The aim of the study is to investigate the effect of tablets containing probiotic candidate strains, on gingival inflammation and the levels of selected pro- and anti-inflammatory cytokines in gingival crevicular fluid (GCF). A secondary aim is to describe the effect of the tablets on the salivary microbiome. The null hypothesis is that the clinical measurements, levels of cytokines and microbial composition of saliva will not differ from baseline or between the study and control group.
The study is planned as a double-blind; placebo controlled randomized trial with two parallel arms. The intervention period is planned to be 4 weeks.
80 participants are planned to be enrolled after informed consent and then randomly allocated to either the probiotic group or the placebo group.
The participants are randomly assigned to one of the study groups and given supply of either probiotic tablets or placebo tablets.
The probiotic tablets contain Lactobacillus rhamnosus PB01 and Lactobacillus curvatus P2-2 at a dose of 1 * 109 CFU(Colony Forming Units)/tablet. The participants will take two tablets a day for four weeks. Follow up registrations are conducted after two weeks, four weeks and six weeks.
At each visit, saliva and GCF will be collected and then plaque index (PI)) and bleeding on probing (BOP) will be registered.
All data will be processed with SPSS software (v 22.0; Chicago, Ill, USA). The follow-up values are compared to baseline within each group by Wilcoxon paired two-sided test and differences between groups are analyzed by Wilcoxon unpaired test. A p-value < 0.05 is considered statistical significant.
The participants are fully covered by the patient insurance of The School of Dentistry which cover any damage to the trial participant during the study .There is no expected side effects to the treatment with probiotics. Probiotics are generally considered safe (GRAS: Generally Recognized As Safe) by The European Food Safety Authority (EFSA).
The participants will not benefit directly from the treatment, but the knowledge gained from the study might contribute to the prevention of microbial derived illnesses in the mouth, e.g. caries and periodontitis, in the future. The sample collection does not cause any discomfort to the participants and the tablets have no known side effects. Therefore, the personal benefit of the participants corresponds to the minimal risk and discomfort to the participants.
详细描述
Background:
The human saliva offers an easy accessible and non-invasive opportunity to study bacterial interactions as well as biomarkers of health and disease. The Human Microbiome Project has provided insights that the biofilms inside and outside our bodies have co-evolved with mankind and play an important role for health. This is also true for the oral cavity in which the microbiota does not play a passive role but actively contributes to the maintenance of oral health. However, certain ecological shifts in the microbiome allow pathogens to manifest and cause oral diseases. According to the ecological plaque hypothesis, caries and periodontitis are the result of environmentally induced overgrowth of aciduric and proteolytic species, respectively.
Bacteriotherapy is the term used when a harmless effector strain is implanted in the host's microflora to maintain or restore a natural microbiome by interference and/or inhibition of other microorganisms, and especially pathogens. This might open up alternative ways of fighting infectious diseases with less harmful side effects and may also help in the treatment of disorders that seem to have nothing to do with bacteria, such as asthma, obesity and diabetes. Probiotic bacteria, defined as "Live microorganisms which, when administered in adequate amounts, confer a health benefit on the host" (WHO), are commonly suggested candidates for bacteriotherapy. The potential mechanisms of action are still not fully understood but it seems clear that there are local (direct) as well as systemic (indirect) effects. According to Reid the potential avenues are: i) co-aggregation with pathogens and growth inhibition, ii) bacteriocin and hydrogen peroxide production, iii) competitive exclusion through antagonistic activities on adhesion sites and nutrition, iv) systemic immunomodulation.
In vitro studies have shown effect on co-aggregation and growth inhibition and clinical studies have shown effect on clinical parameters of gingival inflammation but still little is known about the immunomodulatory effect and the host-microbe interaction.
Periodontal diseases are among the most widespread infectious diseases in man and can lead to tooth loss. If left untreated gingivitis can lead to periodontitis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •presence of at least two buccal marginal sites with moderate gingival inflammation according to the Löe index with a probing depth of ≤ 5 mm
排除标准
- •regular intake of probiotic bacteria
- •pregnancy
- •intake of antibiotics within the last two months before baseline
- •low stimulated saliva rate (0,8 ml/min)
- •rampant decay with several untreated caries lesions
结局指标
主要结局
Cytokines in GCF: INFγ, TNF-α, IL-8, IL-10 and IL-12 (ng/uL)
时间窗: Baseline, two weeks, four weeks, 6 weeks
Change between timepoints
Plaque Index
时间窗: Baseline, two weeks, four weeks, 6 weeks
Change between timepoints. Amount of plaque according to Loe Index
Number of sites with Bleeding on Probing
时间窗: Baseline, two weeks, four weeks, 6 weeks
Change between timepoints
次要结局
- Salivary microbiome (ng/UL)(Baseline, two weeks, four weeks, 6 weeks)
研究者
Mette Kirstine Keller
Assistant Professor
University of Copenhagen