Identification of Physiological Biomarkers of Gastro-intestinal Discomforts Induced by Milk Consumption
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Changes from baseline in plasmatic concentration of milk-derived peptides following milk ingestion.
研究概览
简要总结
This study aims to explore digestibility of lactose and milk proteins, gut permeability, microbiota composition and psychological wellbeing status in healthy subjects who are non-habitual milk consumers due to milk-related gastro-intestinal discomfort in comparison with healthy and habitual milk consumers.
详细描述
Individuals reporting digestive disorders associated to milk and dairy products consumption increase worldwide, but in many cases this condition is not associated with a well documented diagnosis of lactose intolerance or casein allergy. Some investigators hypothesize that these disorders (in the absence of any diagnosis of disease) may be due to certain peptides forming during milk digestion. Further evidence support the hypothesis that other factors, such as a lacking activity of intestinal brush border enzymes, an altered gut permeability, and/or a specific gut microbiota composition, may be involved in the onset of gastrointestinal (GI) discomforts induced by milk consumption. Indeed, all these factors could modulate the amount and type of peptides and lactose skipping digestion and passing through the intestinal mucosa, leading to effects on GI motility and gastro-intestinal hormone secretion. Similarly, due to its implications in homeostatic and non-homeostatic regulation of eating behaviour as well as in pain-regulating processes, a role of endocannabinoid system (ECs) in the evolution of GI symptoms post-milk consumption could be hypothesized.
In this study, the digestibility of lactose and milk proteins will be explored in healthy subjects who are non-habitual milk consumers (NHMC) because of gastro-intestinal discomforts induced by milk ingestion, in comparison with healthy and habitual milk consumers (HMC). The gut permeability, the composition of intestinal microbiota and the psychological wellbeing status of subjects will be also investigated and compared in the 2 groups.
The study design, after the enrollment of participants based on pre-recruitment questionnaires and a lactose breath test, includes a gut permeability test and a milk test.
The potential eligibility of subjects to participate in this study will be assessed through pre-recruitment questionnaires, collecting personal and socio-demographic data of volunteers, information about milk consumption habits and associated symptoms, general information about health (anthropometry, health status, smoking and alcohol consumption habits), household environment, information on volunteer's consideration about milk product and its consumption, and food habits.
Potential eligible subjects who will sign the informed consent form, will be assessed for final eligibility by mean of a lactose breath test, performed according to the protocol approved during the Rome Consensus Conference (2009). GI symptoms will be also recorded by subjects, in parallel with H2 measurements in breath samples and up to 24 hours from the beginning of the test, by mean of Visual Analogue Scales (VAS).
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Drinking milk (maximum 150 ml/week for non-habitual milk consumers and minimum of 700 ml/week for habitual milk consumers)
- •BMI between 18.5 - 30 kg/m2
- •Available for three visits (with one week in between).
- •Willing to drink 250 ml of milk in fasting condition within 10 min
- •Written informed consent
- •Negative lactose breath test result (increase in H2 concentrations < 20 ppm vs basal value) and without symptoms or with any symptoms except "vomiting" and "Loose, mushy or watery stools"
- •Lactose malabsorbers (increase in H2 concentrations > 20 ppm vs basal value but without symptoms)
排除标准
- •Presence of any relevant organic, systemic or metabolic disease or abnormal laboratory values.
- •Ascertained intestinal organic diseases, including celiac disease or inflammatory bowel diseases.
- •Previous major abdominal surgeries.
- •Active malignancy of any type, or history of a malignancy (patients with a history of other malignancies that have been surgically removed and who have no evidence of recurrence for at least five years before study enrolment are also acceptable).
- •Untreated food intolerance.
- •Lactose intolerant
- •Assumption of probiotics or topic and/or systemic antibiotic therapy during the last month.
- •Systematical/frequent assumption of contact laxatives.
- •Pregnant and lactating women.
- •Inability to conform with protocol.
- •Treatment with any investigational drug within the previous 30 days.
- •Recent history or suspicion of alcohol abuse or drug addiction.
- •Subjects having symptoms of "vomiting" and "Loose, mushy or watery stools" at any level of severity following milk consumption and the lactose breath test
结局指标
主要结局
Changes from baseline in plasmatic concentration of milk-derived peptides following milk ingestion.
时间窗: baseline and at 0.5, 1, 2, 4 and 6 hours after milk ingestion.
Measure of casein digestion-derived peptides (beta-casomorphins and all known peptides derived from milk proteins) in plasma samples by mean of HPLC-MS/MS.
Changes from baseline of insulin plasmatic levels following milk ingestion.
时间窗: baseline and at 0.5, 1, 2, 4 and 6 hours after milk ingestion.
Measure of insulin by mean of Luminex kits in plasma samples pre-treated with aprotinin.
Changes from baseline of glucose-dependent insulinotropic peptide (GIP) plasmatic levels following milk ingestion.
时间窗: baseline and at 0.5, 1, 2, 4 and 6 hours after milk ingestion.
Measure of GIP by mean of Luminex kits in plasma samples pre-treated with aprotinin.
Changes from baseline of glucagon-like peptide 1 (GLP-1) plasmatic levels following milk ingestion.
时间窗: baseline and at 0.5, 1, 2, 4 and 6 hours after milk ingestion.
Measure of GLP-1 by mean of Luminex kits in plasma samples pre-treated with aprotinin.
Changes from baseline of glucagon plasmatic levels following milk ingestion.
时间窗: baseline and at 0.5, 1, 2, 4 and 6 hours after milk ingestion.
Measure of glucagon by mean of Luminex kits in plasma samples pre-treated with aprotinin
Changes from baseline of c-peptide plasmatic levels following milk ingestion.
时间窗: baseline and at 0.5, 1, 2, 4 and 6 hours after milk ingestion.
Measure of c-peptide by mean of Luminex kits in plasma samples pre-treated with aprotinin.
Changes from baseline of ghrelin plasmatic levels following milk ingestion.
时间窗: baseline and at 0.5, 1, 2, 4 and 6 hours after milk ingestion.
Measure of ghrelin by mean of Luminex kits in plasma samples pre-treated with aprotinin.
Changes from baseline of leptin plasmatic levels following milk ingestion.
时间窗: baseline and at 0.5, 1, 2, 4 and 6 hours after milk ingestion.
Measure of leptin by mean of Luminex kits in plasma samples pre-treated with aprotinin.
Changes from baseline in serum levels of endocannabinoids and N-acyl-ethanolamines response following milk ingestion.
时间窗: baseline and at 0.5, 1, 2, 4 and 6 hours after milk ingestion.
Measure of endocannabinoids N-acyl-ethanolamines in serum by mean of HPLC-MS/MS
Increases from baseline in urinary concentration of lactose following milk ingestion.
时间窗: baseline and time intervals (0-2, 2-4, 4-6, 6-8, 8-12 and 12-24 hours) following milk ingestion.
Measure of lactose and galactose + glucose excreted in urine samples by mean of high pressure liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS).
次要结局
- Changes from baseline in plasmatic concentration of milk-derived aminoacids following milk ingestion.(baseline and at 0.5, 1, 2, 4 and 6 hours after milk ingestion.)
- Changes from baseline of glycaemia following milk ingestion.(baseline and at 0.5, 1, 2, 4 and 6 hours after milk ingestion.)
- Changes from baseline in urinary concentration of indican over 24 h following milk ingestion(baseline and time intervals (0-6 and 6-24 hours) after milk ingestion.)
- Changes from baseline in gastro-intestinal symptoms developed after milk ingestion.(Baseline and at 0.5, 1, 2, 4, 6, 8, 12 and 24 hours after milk ingestion.)
- Concentration of baseline serum DPPIV(baseline)
- Activity of serum DPPIV(baseline and at 0.5, 1, 2, 4 and 6 hours after milk ingestion.)
- Association of GI symptoms with appetite, glycaemia, plasmatic GI hormones and milk-derived peptides/aminoacids over the first 6 hours post milk consumption, as well as with urinary lactose and galactose + glucose over 24 hours post milk consumption.(Baseline and 0.5, 1, 2, 4, 6 hours post milk ingestion for blood biomarkers, and at baseline and time intervals (0-2, 2-4, 4-6, 6-8, 8-12, 12-24 hours) post milk ingestion for analytes in urines.)
- Increases from baseline in urinary concentration of lactulose, mannitol and sucralose over 24 h after oral challenge as markers of intestinal permeability.(baseline and time intervals (0-5 and 5-24 hours) after oral challenge.)
- Gut microbiota composition(One sample)
- Prevalence of lactose malabsorption in the two groups (assessed with Lactose Breath Test).(During recruitment step)
- psychological profile(During recruitment step)
研究者
Paola Vitaglione
Associate Professor
Federico II University