Impact of a Synbiotic Containing Fructo-oligosaccharides and Bifidobacteria in Middle-aged Adults

Study Overview
=================
Brief Summary
-----------------
The aim of the study is to evaluate the impact of a synbiotic containing fructo-oligosaccharides (FOS) and Bifidobacteria (VES002 LMG P-28149) on intestinal transit in middle-aged subjects characterized by a low number of defecations per week.

Detailed Description
-----------------
Middle-aged subjects, who met ROME III criteria for constipation, received daily two sachets of either synbiotic or for 5 days, then they received daily 1 sachet for the next 25 days. The primary endpoint of this trial is to evaluate the effect of supplementation in synbiotic containing fructo-oligosaccharides (FOS) and Bifidobacteria (VES002 LMG P-28149) on intestinal transit in middle-aged subjects characterized by a few bowel movements per week. The secondary endpoints are to evaluate both clinical criteria such as changes in stool appearance, quality of life and mood, relief and satisfaction of participants; and biological criteria such as changes in markers of gut function, low-grade chronic inflammation markers and gut microbiota composition. The safety of product use and compliance are also evaluated Synbiotic group. The dietary supplement under study was composed of fructo-oligosaccharides - FOS: 4.95 gr / sachet and Bifidobacterium animalis lactis: VES002 (LMG P-28149): 5 billion / sachet. Sachets of powder were diluted in a in 200 ml of water at room temperature to be taken before breakfast. Doses were 2 sachets per day for the first 5 days and then 1 sachet per day for the next 25 days. Placebo group. The placebo looked strictly identical to the synbiotic and contained only excipients (60% maltodextrin / 40% sucrose). Sachets of powder were diluted in a in 200 ml of water at room temperature to be taken before breakfast. Doses were 2 sachets per day for the first 5 days and then 1 sachet per day for the next 25 days.

Official Title
-----------------
Impact of a Synbiotic Containing Fructo-oligosaccharides and Bifidobacteria on Stool Frequency and Biological Markers in Middle-aged Adults: a Randomized, Double-blind, Placebo-controlled Clinical Trial

Conditions
-----------------
Constipation

Intervention / Treatment
-----------------
* Dietary Supplement: Synbiotic
* Dietary Supplement: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Free and informed consent Healthy male and female aged 50-70 years Patient with ≥1 and ≤3 bowel movements per week in the month before the selection visit and in the two weeks before the enrolment visit. At least one in four bowel movements had to involve hard faeces or separate lumps of faeces (Bristol scale class 1 in the three months before enrolment). Exclusion Criteria: Subjects who, in the 30 days before the selection visit or at the time of the visit, had taken drugs, dietary supplements or any foodstuff enhanced in or containing substances, bacteria or yeasts that might have an effect on primary and secondary outcomes. Such products were also prohibited throughout the study. Subjects on a particular diet or who were under medical treatment that in the investigator's viewpoint might interfere with the evaluation of the study criteria Subjects who drink more than three glasses of wine a day or two 25 cl glasses of beer a day, or one glass of spirits per day. Subjects who drink more than five cups of coffee per day; Subjects with a body mass index (BMI) of more than 30, Subjects with type I or II diabetes, Subjects with constipation attributable to an organic or anatomical cause; Subjects with a history of chronic or inflammatory gastro-intestinal disease; Subjects with a history of digestive tract operation including bariatric surgery;

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Synbiotic group<br>The synbiotic was composed of fructo-oligosaccharides (FOS): 4.95 g/ sachet and Bifidobacterium animalis lactis: 5 billion / sachet (n=13) | Dietary Supplement: Synbiotic<br>* Middle-aged subjects, who met ROME III criteria for constipation, received daily two sachets of synbiotic (Bifidobaterium animalis lactis Vesalius 002 and Fructo-Oligosaccharrides) for 5 days, then they received daily 1 sachet for the next 25 days<br>|
| Placebo Comparator: Placebo group<br>A placebo was composed of maltodextrin (60%) and sucrose (40%) : 5 g /sachet (n =14) | Dietary Supplement: Placebo<br>* Middle-aged subjects, who met ROME III criteria for constipation, received daily two sachets of placebo (maltodextrin and sucrose) for 5 days, then they received daily 1 sachet for the next 25 days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| intestinal transit | stool frequency and consistency were investigated through daily self-assessment using the Bristol Stool Form Scale (BSFS). The BSFS classifies stools into 7 categories, including type 1, separate hard lumps, like nuts; type 2, sausage-shaped, but lumpy; type 3, like a sausage but with cracks on the surface; type 4, like a sausage or snake, smooth and soft; type 5, soft blobs with clear-cut edges; type 6, fluffy pieces with ragged edges, a mushy stool; type 7, watery, no solid pieces | daily evaluation (day-14 to day 30) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| stool consistency | self-assessment using the Bristol Stool Form Scale | daily evaluation (day-14 to day 30) | 
| evaluation of quality of life | Mental and physical wellbeing were assessed before (d-14) and after intervention (d30) through the Short-Form 12-item (SF-12) questionnaire consisting of 12 questions relating to: physical health problems, bodily pain, general health perceptions, vitality (energy/fatigue), social functioning, role limitations and general mental health (psychological distress and psychological well-being) | day 0 and day 30 | 
| mood | Mood alterations was investigated through daily self-assessment using the Brief Mood Introspection Scale (BMIS), consisting of 16 mood adjectives (Lively, Drowsy, Happy, Grouchy, Sad, Peppy, Tired, Nervous, Caring, Calm, Content, Loving, Gloomy, fed up, Jittery, Active)47. Subjects were asked to circle the phrases describing their present mood (with XX = definitely do not feel; X = do not feel; V = slightly feel; VV = definitely feel on the diverse adjectives). | daily evaluation (day-14 to day 30) | 
| abdominal pain and intestinal discomfort | Evaluation based on VAS ( 0 - 100mm). 0 for no pain and 100 for unbearable pain | day -14 and day 30 | 
| plasma inflammatory markers (pg/ml) | Plasma cytokines (interleukin (IL)-1alpha, IL-6, IL-8, IL-10, IL-17a, monocyte chemotactic protein-1 (MCP-1), interferon (IFN) gamma and tumor necrosis factor (TNF) alpha) measured by multiplex immunoassay (Millipore, Belgium) using Luminex® xMap® technology (Biorad, Nazareth, Belgium) | day 0 and day 30 | 
| plasma gut peptides (pg/ml) | pancreatic polypeptide (PP), glucose-dependent insulinotropic peptide (GIP), leptin, ghrelin measured by multiplex immunoassay (Millipore, Belgium) using Luminex® xMap® technology (Biorad, Nazareth, Belgium) | day 0 and day 30 | 
| microbiota composition | 16S rDNA profiling, targeting V1-V3 hypervariable region and sequenced on Illumina MiSeq | day 0 and day 30 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
probiotics, constipation, FOS