Clinical trial NCT01874301: Probiotics and Gut Health
Official title: Evaluation of Changes in Gut Transit Time and Gastrointestinal Symptoms Following the Consumption of a Probiotic Food Product in Adults With Constipation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Constipation
Lead sponsor: Société des Produits Nestlé (SPN)
Sponsor class: INDUSTRY
First posted: 2013-06-11
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Gastrointestinal discomfort regularly affects \>25% of the population worldwide. One of the major contributors to Gastrointestinal discomfort is constipation, which has a prevalence of \~15%, and symptoms of which have a significant negative impact on the sufferer's quality of life. One of the hallmarks of chronic constipation is slow progression of contents through the gut (i.e. slow gut / colonic transit time), which may be associated with hard stools that are difficult to expel. Previous studies have shown that probiotics improve colonic transit times in constipated patients. In addition, several other studies, employing a range of different probiotic strains, have shown a significant increase in defaecation frequency and improvement in stool consistency. However, the clinical relevance of these results is uncertain, due to small sample sizes and limitations in study methodology. The current study is designed to compare changes in gut transit time and gastrointestinal symptoms following 4 weeks consumption of a probiotic strain in a randomized, double-blind, placebo-controlled manner, in adults with constipation.

Detailed description: This is an adaptive, parallel, double-blinded, randomized, placebo-controlled, stratified clinical study, comparing three study arms (two quantities of the probiotic active component and one placebo)with equal allocation ratio. Recruitment of subjects to the low quantity of the probiotic will be after fulfilling certain criteria at interim. After half of the subjects in the two study groups of high quantity and placebo have completed the study (40 subjects), an interim analysis will be performed. Depending on the observed effect size and the conditional power, the study may be stopped for futility, continued with the two groups or continued with inclusion of the third group of low dose probiotics.

Eligibility criteria: Inclusion Criteria:

* Adult men or women
* female subjects of child-bearing potential must be willing to use a reliable method of contraception throughout the study period
* Age 18 - 65
* BMI: 18.5 - 29.9 kg/m2
* Symptoms of constipation for a minimum of 3 months
* Recruitment based on simplified core ROME III diagnostic criteria for functional constipation (based on specific screening questions):a). average Bristol stool type of 1 - 4 AND frequency of 1 - 3 spontaneous bowel movements (SBMs) per week b). plus at least ONE of: straining on at least 25% of defaecations; sensation of incomplete evacuation on at least 25% of defaecations; sensation of anorectal obstruction / blockage on at least 25% of defaecations; use of manual manoeuvres on at least 25% of defaecations.
* Cleveland Clinic constipation score (CCCS) of 8-15
* Willing and able to consume a milk-based product daily for 4 weeks
* Low-moderate fibre intake (≤18g) determined by the semi-quantitative food intake screener known as the Block Fibre Screener
* No regular use of fibre supplementation (e.g. Fybogel, Lactulose) over the week prior to the screening visit, and no more than 6 standard doses in the past 1 month prior to the screening visit. Also, willing to discontinue fibre supplementation and other probiotics, prebiotics, fermented milk, yoghurt or laxatives at least 2 weeks prior to and during the consumption phase and the follow-up phase
* Ability to understand the patient information sheet and instructions in English, and able to provide informed consent

Exclusion Criteria:

* Subjects who report lactose intolerance and/or are allergic to cow milk protein or soya
* Regular consumption of probiotics, fibre supplements (including prebiotics), fermented milk, yogurt, laxatives, or those unwilling to discontinue these at least 2 weeks prior to and during the study
* Pregnant or breast-feeding women
* Ongoing other diagnosed gastrointestinal disease or complication (e.g. IBS, Crohn's disease, Coeliac disease, chronic diarrhoea, etc.)
* Any clinical relevant abnormalities in the screening visit medical examination or alarm features such as sudden unintentional weight loss, rectal bleeding, recent change in bowel habit (\<3 months), abdominal pain and stool positive for occult blood
* Prior abdominal surgery (including gastric bypass or laparoscopic banding), except cholecystectomy and appendicectomy
* Neurologic diseases such as multiple sclerosis, stroke, spinal cord injury, Hirschsprung disease
* Ongoing therapy with drugs known to affect gut motility, such as prokinetic agents (such as metoclopramide, domperidone, erythromycin, azithromycin), anti-emetic agents, anxiolytics (such as benzodiazepines), antidepressive agents (such as trycyclics, SSRI's etc.), narcotic analgesic agents (such as methadone, fentanyl), anticholinergic agents for IBS, medications for constipation (including enemas, cathartics, polyethylene glycol solutions), 5HT3 antagonists, anti-diarrheal agents (such as loperamide), opiate agents used to treat diarrhoea, NSAIDs (more than once daily), other antibiotics taken during or within 4 weeks of study onset, magnesium-containing antacids
* Illness that may preclude the subject's ability to complete the study or that may confound the study outcomes (e.g. bowel cancer, prostate cancer, terminal illness, severe cardiovascular disease, chronic renal failure or eating disorders) or any other serious illness resulting in \>2 weeks inability to work in the 3 months before the study start
* Subjects with co-morbid illnesses such as cardiovascular, endocrine, renal or other chronic disease likely to affect gut motility or limit normal functions (e.g. reduced mobility or increased fragility)
* HADS score of \>11
* Ongoing alcohol, drug, or medication abuse
* Self-reported symptoms of pelvic organ prolapse
* Moderate or severe active local anorectal problems such as recurrent anal fissures, bleeding, large prolapsing haemorrhoids, etc
* Participation in another study with any investigational product within 3 months of screening
* Investigator believes that the participant may be uncooperative and/or noncompliant and should therefore not participate in the study

Primary outcomes:
measure: Whole gut transit time- 2 groups
timeFrame: After 2 weeks consumption of the study product
Secondary outcomes:
measure: Regional colonic transit time- all groups
timeFrame: After 2 weeks consumption of the study product
measure: Whole gut and Regional colonic transit time- all groups
timeFrame: After 4 weeks consumption of the study product
measure: Whole gut transit time- all groups
timeFrame: After 2 weeks consumption of the study product
measure: Response to the Patient assessment of constipation symptoms (PAC-SYM) - all groups
timeFrame: After 2&4 weeks consumption of the study product
measure: Cleveland Clinic constipation score - all groups
timeFrame: After 1&2&4 weeks consumption of the study product
measure: Stool frequency- all groups
timeFrame: After 2&4 weeks consumption of the study product
measure: Stool consistency - all groups
timeFrame: After 2&4 weeks consumption of the study product
measure: Response to the constipation quality of life (PAC-QOL)questionnaires - all groups
timeFrame: After 2&4 weeks consumption of the study product
measure: Tolerance to the study product- all groups
timeFrame: After 2&4 weeks consumption of the study product
measure: Global Constipation Symptom Score - all groups
timeFrame: After 1&2&4 weeks consumption of the study product
measure: Ease of passage - all groups
timeFrame: After 2&4 weeks consumption of the study product
Other outcomes:
measure: Correlation between lifestyle, diet and blood/stool biomarkers with gut function and symptoms- all groups
timeFrame: After 2&4 weeks consumption of the study product
measure: Long-term changes in gut function and gastrointestinal symptoms
timeFrame: After 4 weeks follow-up (week 8)
measure: Adverse Events
timeFrame: Through the study product consumption period (4 weeks)
Locations:
city: London
country: United Kingdom
facility: Wingate Institute, Queen Mary University of London
Study officials:
affiliation: Wingate Institute, Queen Mary University of London
name: Mark Scott, PhD
role: PRINCIPAL_INVESTIGATOR
References: