Gut Microbial Profiles in Fermentable Carbohydrate Induced Bloating: an Exploratory Double-blind, Randomized Cross-over, Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 2
- 主要终点
- Bloating as measured by the Gastrointestinal Symptom Rating Scale (GSRS) (Primary clinical response): end of first intervention period (day 7)
研究概览
简要总结
This study is an exploratory study aimed at gaining a greater understanding of the cause of abdominal bloating in response to two distinct fibre types. This is a single-center, interventional double blinded randomized cross-over study. Each participant will consume each of the study products (placebo, fibre 1 and fibre 2) for a 7-day period with a 3-week washout period in between. Outcomes will be measured before and after each intervention period.
详细描述
The investigators have 4 hypotheses linked to 4 research questions that will be answered by this research:
Hypothesis 1: participants with self-reported functional bloating in response to either fibre-1 or fibre-2, but not both, will respond symptomatically to fibre-1 or fibre-2, defined as 'fibre-1 responders' and 'fibre-2 responders'.
Hypothesis 2: participants with functional bloating who are 'fibre-1 responders' will be distinguishable from 'fibre-1 non-responders', and 'fibre-2 responders' will be distinguishable from 'fibre-2 non-responders', based upon faecal microbial profiles identified using faecal metagenomics, transcriptomics and metabolites at baseline and following the fibre-1 and fibre-2 interventions.
Hypothesis 3: the microbiota, clinical and nutritional profiles of participants with functional bloating will be interrelated and these relationships will be distinguishable between 'fibre-1 responders', 'fibre-1 non-responders', and 'fibre-2 responders' and 'fibre-2 non-responders'.
Hypothesis 4: participants with visceral hypersensitivity will have different faecal microbiota and will be more likely to be a 'fibre-1 responders' or 'fibre-2 responders' than 'non-responders'.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Double blinded
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
- •Healthy adults (18-60 years of age inclusive, and BMI 19-29 kg/m2 inclusive) who fulfil criteria for functional bloating as per Rome IV Criteria (to be assessed at screening phone call).
- •Individuals willing to provide consent and follow the protocol
- •Individuals who report that due to perceived trigger food avoidance, symptoms are well controlled i.e. report that over the past 3 days they have had absent or mild bloating on ≥2 days.
- •Individuals that do not fulfil Rome IV criteria for irritable bowel syndrome, functional constipation or functional diarrhoea
- •Individuals that report heightened bloating in response to foods predominantly high in just one type of study fibre i.e not those that report bloating in response to foods high in both. The goal will be to recruit equal proportion of each.
- •Individuals that are not diagnosed with any other chronic gastrointestinal disease or condition including inflammatory bowel disease, coeliac disease.
排除标准
- •Excessive habitual intake of fructans, galacto-oligosaccharides, polyols or fructose, as defined by clinician as the sole cause of symptoms.
- •Individuals with specific diets (eg: strict low-FODMAP).
- •Participation in another clinical trial within the past 4 weeks
- •Subject with known or suspected allergy to any component of the study product(s).
- •Individuals receiving treatment for anorexia, weight loss, or any form of treatment likely to interfere with metabolism or dietary habits.
- •Vulnerable subjects defined as individuals whose willingness to volunteer in the clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate. (Examples are members of a group with a hierarchical structure linked to the Investigator or to the Sponsor, such as students, subordinate hospital and laboratory personnel, employees of the Investigator or of the Sponsor).
- •Individuals with antibiotics or proton pump inhibitor (e.g. omeprazole, lansoprazole and esomeprazole, pantoprazole, Rabeprazole) use within the previous 2 months
- •Individuals with current use of medication with potential central nervous system effects as judged by the investigator.
- •Individuals with previous digestive surgery (except for appendectomy and cholecystectomy performed more than 2 years ago).
- •Athletes as defined as performing daily strenuous daily exercise for more than 1.5 hours at a time.
- •Oral disease that may impact on breath sampling e.g. gingivitis, halitosis, oral thrush, candidiasis.
- •Individuals starting or routinely taking drugs (occasional use is acceptable) that might modify gastrointestinal function such as:
- •Prokinetic agents e.g. metoclopramide (Reglan), tegaserod (Zelnorm), domperidone (Motilium),
- •Anti-emetics agents
- •Corticosteroids
- •Narcotic analgesic agents e.g. methadone, fentanyl
- •Anticholinergic agents for irritable bowel syndrome
- •Medications for constipation e.g. enemas, cathartics, polyethylene glycol solutions, and lactulose.
- •5HT3 antagonists e.g. alosetron and ondansetron.
- •Anti-diarrheal agents e.g. Imodium (loperamide)
- •Opiate agents used to treat diarrhoea.
- •NSAIDs e.g. ibuprofen
- •Histamine2 blockers e.g. cimetidine (Tagamet), famotidine (Pepcid), and ranitidine hydrochloride (Zantac), nizatidine (Axid)
- •Antacids e.g. Gaviscon, Maalox, Tums, or any that contain magnesium or aluminium
- •Supplements used to treat bloating: activated charcoal, alpha galactosidase
- •Women who report they are pregnant/lactating/planning pregnancy
- •Recent/ongoing consumption of probiotics/prebiotic supplements (past 4 weeks)
- •Anticipated changes to consumption of naturally probiotic/prebiotic containing foods e.g. yogurt with live cultures or cereals with chicory etc, in the next 2 months
- •Anticipated changes to smoking habits in the next 2 months
- •Ongoing abuse of alcohol (>40 units per week)/non-prescription drugs/other medication
结局指标
主要结局
Bloating as measured by the Gastrointestinal Symptom Rating Scale (GSRS) (Primary clinical response): end of first intervention period (day 7)
时间窗: Day 7
As this is an exploratory study to determine the underlying mechanisms of bloating the investigators have identified a primary and secondary symptom responder definition (those that become bloated in response to the intervention) that will be used to examine and compare the research outcome measures. The primary responder definition is: reporting moderate or severe bloating (a score of 2 or 3) on at least two of the final three days of the fibre-1 or fibre-2 challenge, measured using the Gastrointestinal Symptoms Rating Scale (GSRS), which rates individual gastrointestinal symptoms on a 4-point Likert scale (0-3). The primary responder definition of response will also be measured at the end of the placebo period.
Bloating as measured by the Gastrointestinal Symptom Rating Scale (GSRS) (Primary clinical response): end of third intervention period (day 63)
时间窗: Day 63
As this is an exploratory study to determine the underlying mechanisms of bloating the investigators have identified a primary and secondary symptom responder definition (those that become bloated in response to the intervention) that will be used to examine and compare the research outcome measures. The primary responder definition is: reporting moderate or severe bloating (a score of 2 or 3) on at least two of the final three days of the fibre-1 or fibre-2 challenge, measured using the Gastrointestinal Symptoms Rating Scale (GSRS), which rates individual gastrointestinal symptoms on a 4-point Likert scale (0-3). The primary responder definition of response will also be measured at the end of the placebo period.
Bloating as measured by the Gastrointestinal Symptom Rating Scale (GSRS) (Primary clinical response): end of second intervention period (day 35)
时间窗: Day 35
As this is an exploratory study to determine the underlying mechanisms of bloating the investigators have identified a primary and secondary symptom responder definition (those that become bloated in response to the intervention) that will be used to examine and compare the research outcome measures. The primary responder definition is: reporting moderate or severe bloating (a score of 2 or 3) on at least two of the final three days of the fibre-1 or fibre-2 challenge, measured using the Gastrointestinal Symptoms Rating Scale (GSRS), which rates individual gastrointestinal symptoms on a 4-point Likert scale (0-3). The primary responder definition of response will also be measured at the end of the placebo period.
次要结局
- Secondary response measure: Adequate relief of bloating symptoms assessed by the Global Symptom Questionnaire (GSQ) (Secondary clinical response)(Day 7, day 21, day 28, day 35, day 56, day 63)
- Clinical profile: Gas-related gastrointestinal symptom profile assessed by the Intestinal Gas Questionnaire (IGQ)(Gas-related gastrointestinal symptom profile will be assessed after each intervention period (days 7, 35 and 63) and after each washout period (days 28 and 56) and once at a control timepoint (day 21).)
- Clinical profile: Gastrointestinal symptom profile assessed by the Gastrointestinal symptom rating scale (GSRS)(Gastrointestinal symptoms profile will be assessed after each intervention period (days 7, 35 and 63) and after each washout period (days 28 and 56) and once at a control timepoint (day 21).)
- Clinical profile: Stool form and frequency using the Bristol Stool Form Scale (BSFS)(The BSFS for each stool passed will be recorded in a 7-day diary and will be assessed after each intervention period (days 7, 35 and 63) and after each washout period (days 28 and 56) and once at a control timepoint (day 21).)
- Clinical profile: Abdominal girth (cms)(Abdominal girth will be recorded daily in a 7-day diary and will be assessed after each intervention period (days 7, 35 and 63) and after each washout period (days 28 and 56) and once at a control timepoint (day 21).)
- Clinical profile: Visceral hypersensitivity - rectal barostat(Visceral hypersensitivity will be measured during the first washout period (between day 7 and day 28))
- Microbiome profile: Faecal transcriptomics from stool sample (microbiota activity) (metatranscriptomics profiling)(Days 21, 28, 35, 56, and 63)
- Microbiome profile: Faecal Short-Chain Fatty Acids (SCFA) (gas-liquid chromatography) from stool sample(Days 21, 28, 35, 56, and 63)
- Nutrition profile: Energy and nutrient intake(Energy and nutrient intake will be recorded daily in a 7-day diary and will be assessed after each intervention period (days 7, 35 and 63) and after each washout period (days 28 and 56) and once at a control timepoint (day 21).)
- Nutrition profile: Fermentable oligo-, di-, mono- saccharide and polyol (FODMAP) intake(Dietary intake will be recorded daily in a 7-day diary and will be assessed after each intervention period (days 7, 35 and 63) and after each washout period (days 28 and 56) and once at a control timepoint (day 21).)
- Microbiome profile: Faecal Volatile Organic Compounds (VOC) (gas-chromatography mass-spectrometry) from stool sample(Days 21, 28, 35, 56, and 63)
- Microbiome profile: Fermentation (direct breath hydrogen and methane tests) using Gastrogenius breath-gas analyser(Days 21, 28, 35, 56, and 63)