BIFI-OBESE: Effect of Probiotic Bifidobacterium Breve BR03 and Bifidobacterium Breve B632 in Paediatric Obesity
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Change in glucose level during oral glucose tolerance test (OGTT)
研究概览
简要总结
Obesity is a major, public health concern that affects at least 400 million individuals and is associated with severe disorders including diabetes and cancers. Worldwide, the prevalence of overweight and obesity combined in children, adolescents and youth, between 1980 and 2013, increased to 47.1%, with alarming data also in developing countries. Obesity is often caused by imbalance between excessive caloric intake and reduced physical activity.
Recently, microbial changes in the human gut was proposed to be another possible cause of obesity and it was found that the gut microbes from fecal samples contained 3.3 million non-redundant microbial genes. However, it is still poorly understood how the dynamics and composition of the intestinal microbiota are affected by diet or other lifestyle factors. Moreover it has been difficult to characterize the composition of the human gut microbiota due to large variations between individuals.
The role of the digestive microbiota in the human body is still largely unknown, but the bacteria of the gut flora do contribute enzymes that are absent in humans for food digestion. Moreover, the link between obesity and the microbiota is likely to be more sophisticated than the simple phylum-level Bacteroidetes: Firmicutes ratio that was initially identified, and it is likely to involve a microbiota-diet interaction.
Obese and lean subjects presented increased levels of different bacterial populations. It is hypothesized that the obese microbiome is set up to extract more calories from the daily intake when compared to the microbiome of lean counterparts. In addition, a caloric diet restriction impacted the composition of the gut microbiota in obese/overweight individuals and weight loss.
In lean subjects there are Coriobacteriaceae, Lactobacillus, Enterococcus, Faecalibacterium prausnitzii, Prevotella, Clostridium Eubacterium, E. coli and Staphilococcus. By contrast, Bifidobacterium, Methanobrevibacter, Xylanibacter, Bacteroides characterize the composition of lean gut microbiota.
For this reason, in a cohort of obese paediatric subjects with visceral adiposity, the aim of the study is to assess the efficacy of a supplementation with probiotic bifidobacteria with respect to a conventional treatment on weight loss and improvement of cardio-metabolic risk factors.
详细描述
Study design: A single-center pilot open-label randomized control trial. Population: The study will comprise a total of 100 subjects of both sexes, between 6 and 18 years of age, obese, according to the IOTF criteria and with visceral adiposity, as waist circumference ≥ 90th percentile, pubertal stage ≥ 2 according to the Tanner stage, HOMA-IR > 2,5 or insulin > 15 µU/ml, diet naïve or with failure of weight loss (defined as -1 kg/m2 BMI in 1 year).
Inclusion/ Exclusion criteria (see Eligibility Criteria). Intervention: In the first part of the study (Study 1, V0-V1) patients will be randomized in a open-label, into two groups homogeneous for number and sex of the subjects. One group will receive a supplementation of probiotic containing Bifidobacterium breve B632 and Bifidobacterium breve BR03, 15 gtt/die (3x108 CFU/die) and one group will receive a placebo for a total of 2 months of treatment. Both group receives a Standard Diet according to routine care and practice. For patients who wants to continue the study there will be a cross-over study (study 2, V2-V3) after one month of wash-out.
Dietary restriction: The standard diet will be distributed with 55-60% of carbohydrates (45-50% complex and no more than 10% refined and processed sugars), 25-30% lipids and 15% proteins, and will be performed in accordance with the calories of an isocaloric balanced diet calculated throughout the Italian LARN Guidelines for age and gender.
Physical activity: all subjects will receive general recommendations about performing physical activity. Exercise will be conducted daily and will consist of 30 minutes of aerobic physical activity.
Randomization: Participants will be randomly assigned in a 1:1 to probiotic intervention group or placebo group.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The study is a triple blind study in which the treatment or intervention is unknown to the research participant, the individuals who administer the treatment or intervention, and the researchers who assess the outcomes.
入排标准
- 年龄范围
- 6 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •between 6 and 18 years of age
- •obese, according to the IOTF criteria (Cole TJ et al., 2000)
- •pubertal stage ≥ 2 according to the Tanner stage (Tanner et al., 1961)
- •HOMA-IR > 2,5 or insulin > 15 µU/ml
排除标准
- •Adverse reactions to the product or component of the product (allergies...)
- •Genetic obesity (Prader Willi syndrome, Down syndrome), Metabolic obesity (Laurence-biedl syndrome...), endocrinological obesity (Cushinch syndrome, hypotiroidism)
- •Chronic diseases, hepatic or gastroenterological diseases
- •Medical treatment for chronic diseases
- •Probiotic or prebiotic therapies and antibiotic treatment
研究组 & 干预措施
Active group Bifidobacterium breve BR03 and B632
This arm will receive a supplementation of probiotic containing Bifidobacterium breve B632 and Bifidobacterium breve BR03, 15 gtt/die (3x108 CFU/die) once a day.
干预措施: Bifidobacterium breve BR03 and Bifidobacterium breve B632 (Drug)
Placebo group
This arm will receive a supplementation with a same product equal to the active product but without bifidobacterium inside.
干预措施: Placebos (Drug)
结局指标
主要结局
Change in glucose level during oral glucose tolerance test (OGTT)
时间窗: Change from Baseline OGTT (V0) at 2 months (V1), 3 months (V2) and 5 months (V3)
Evaluate if after the treatment with probiotic there is a reduction of glucose values during the OGTT at time 0' e 120' after oral glucose tolerance test.
Change in HOMA-IR index
时间窗: Change from baseline HOMA-IR (V0) at 2 months (V1), 3 months (V2) and 5 months (V3)
Evaluate if after the treatment with probiotic there is a variation of HOMA-IR index.
次要结局
- Metabolic control: Improvement of metabolic risk factors(Change from baseline lipid profile, insulin, leptin, adiponectin, GLP1 (V0) at 2 months (V1), 3 months (V2) and 5 months (V3))
- Change in fecal microbiome(Change from Baseline fecal microbiome (V0) at 2 months (V1), 3 months (V2) and 5 months (V3))
- Change in SCFA (short-chain fatty acids) in fecal samples(Change from Baseline fecal SCFA (V0) at 2 months (V1), 3 months (V2) and 5 months (V3))
研究者
Flavia Prodam
Assoc. Professor in Clinical Nutrition
Azienda Ospedaliero Universitaria Maggiore della Carita