Modulation of Microbial Composition in Ileostomy Patients (INSIDE)

Modulation of Small Intestinal Microbial Composition and Activity,Systemic Immune Adaptation and Blood Transcriptional Changes Induced by 2-wks Consumption With 2 Fermented Milk Products;a Randomized,Exploratory,Cross-over,Double Blind,Controlled Study in Ileostomy Patients

To determine the small intestinal microbiota response in humans to dietary interventions for two consecutive weeks, and to relate this to parameters of intestinal barrier function and immune and metabolic responses in blood, as functional outcome parameters of host physiology

Study Overview

• Status: Completed
• Conditions: Ileostomy - Stoma
• Intervention / Treatment: Dietary supplement: Probiotic 1; Dietary supplement: Probiotic 2; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229 HX
      • Maastricht University Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• • Ileostomy installed at least 3 years prior to participation

  • Free of any complications originating from the colectomy procedure for at least 1 yr prior to participation, with the exception of possible skin irritation at the location of the stoma
  • BMI from 18 till 28 kg/m2
  • Age from 18 till 70 years
  • Available for entire study protocol.
  • For female: If of child bearing potential, female subjects must be using or complying with methods of contraception (such as oral birth control pills, intra-uterine device, double barrier methods (like condoms and spermicide, etc.)

Exclusion Criteria:

• • History of cardiovascular, respiratory, urogenital, hepatic, haematological / immunologic, HEENT (head, ears, eyes, nose, throat), dermatological/connective tissue, musculoskeletal, metabolic/nutritional, endocrine, neurological diseases, allergy, laboratory assessments which might limit participation in or completion of the study protocol, and/or major surgery with the exception of total colectomy, hysterectomy and/or appendectomy.

  • Subject with known lactose intolerance or with known or suspected allergy or hypersensitivity to any component of the study product(s) (milk protein for example) + sucrose + rhamnose
  • Severe gastrointestinal symptoms. In case of mild gastrointestinal symptoms, the principal investigator and the medically responsible MD will judge eligibility to participate.
  • Removal of more than 15 cm of the ileum during or at any moment after the colectomy procedure
  • Abdominal surgery interfering with gastrointestinal function, upon judgment of the principal investigator and the medically responsible MD
  • Use of medication, including proton pump inhibitors, non-steroidal anti-inflammatory drugs interfering with endpoints (but except oral contraceptives), within 14 days prior to and during participation.
  • Consumption of any probiotic or prebiotic supplements or pre- and probiotics containing food products, investigational drugs or participation in any scientific intervention study which may interfere with this study (to be decided by the principal investigator), in the 4 weeks prior to the study and during study participation (E4 PreProbiotics).
  • Use of antibiotics in the 4 weeks prior to the start of study and during study participation
  • Prohibited use of pro-, pre- or synbiotics during study period and three months prior to start of study. A list with forbidden products will be provided'
  • History of any side effects towards intake of pro- or prebiotic supplements of any kind.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Probiotic 1; Fresh fermented dairy drink containing yoghurt ferments consumed as follows: one bottle (100g) OD for 14 consecutive days	Dietary supplement: Probiotic 1; Fresh fermented dairy drink containing yoghurt ferments
Active Comparator: Probiotic 2; Fresh fermented dairy drink containing probiotic strain consumed as follows: one bottle (100g) OD for 14 consecutive days	Dietary supplement: Probiotic 2; Fresh fermented dairy drink containing probiotic strain
Placebo Comparator: Placebo; Acidified dairy drink without ferments consumed as follows: one bottle (100g) OD for 14 consecutive days	Dietary supplement: Placebo; Acidified dairy drink without ferments

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Temporal microbial composition and activity in the small intestine in ileal effluent	The microbiome activity will be determined as a function of the diet by double strand cDNA production and random sequencing of mRNA enriched fractions of total effluent RNA obtained from the effluent samples at the start and end of each intervention period.	2 weeks intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Small intestinal permeability by a multi sugar test (urinary recovery of test sugars)		2 weeks intervention
Gene transcription response in blood by transcriptome patterns.	Transcriptome patterns will be determined in peripheral blood mononuclear cells obtained from blood samples from the participating ileostoma patients	2 weeks intervention
The levels of a panel of peripheral blood biomarkers related to immune, metabolic and hormonal status	A panel of biomarkers will be determined in peripheral blood obtained at the start and end of the intervention periods	2 weeks intervention
The level of whole blood immune responsiveness to a panel of standardized stimuli ex vivo	Peripheral whole blood immune responsiveness towards a subset of bacterial immune-stimuli will be assessed using the standardized truculture system	2 weeks intervention
Morning urine metabolome profiles	The principal analytical methodology employed is mass-spectrometry profiling and can commonly provide reliable quantifications of more than 400 named-metabolites in different body-fluid samples.	2 weeks intervention
Peripheral blood metabolome profiles	The principal analytical methodology employed is mass-spectrometry profiling and can commonly provide reliable quantifications of more than 400 named-metabolites in different body-fluid samples.	2 weeks intervention
The relative survival of bacterial strains (colony forming unit enumeration on semi-selective culture plates)		2 weeks intervention
Short chain fatty acid profiles in ileal effluent		2 weeks intervention
Number of participants with Gastrointestinal symptoms by Visual Analogue Scales		2 weeks intervention
Occurrence and severity of treatment related adverse events		2 weeks intervention

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Investigators: Principal Investigator: Fred Troost, PhD, Maastricht University Medical Center (MUMC+)

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Actual): November 11, 2017
• Study Completion (Actual): November 11, 2017

Study Registration Dates

• First Submitted: September 27, 2016
• First Submitted That Met QC Criteria: September 28, 2016
• First Posted (Estimate): September 30, 2016

Study Record Updates

• Last Update Posted (Actual): August 2, 2018
• Last Update Submitted That Met QC Criteria: July 31, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: probiotics, microbiota, ileostoma
• Other Study ID Numbers: METC 163023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes