The Effects of Prebiotics on Gut Bacterial Parameters, Immune Function & Exercise-Induced Airway Inflammation.
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|ClinicalTrials.gov Identifier: NCT02872675|
Recruitment Status : Recruiting
First Posted : August 19, 2016
Last Update Posted : March 19, 2019
|Condition or disease||Intervention/treatment||Phase|
|Exercised Induced Asthma Asthma||Dietary Supplement: HOST-DM059 Dietary Supplement: Maltodextrin||Not Applicable|
The current study will investigate the effects of prebiotic supplementation on airway inflammation/bronchoconstriction in adults diagnosed with Asthma/Exercise-Induced Bronchoconstriction (A/EIB). Previous research conducted in adults diagnosed with A/EIB has reported significant improvements in pulmonary function following three weeks of prebiotic supplementation. The significant improvements in pulmonary function were attributed to an attenuation of various markers of airway inflammation, potentially regulated by gut microbiota mediated improvements in systemic immune function.
Prebiotics are a type of non-digestible carbohydrate/dietary fibre that can only be digested by certain beneficial bacteria. During the fermentation of prebiotics, beneficial bacteria produce energy/metabolites that can be used to support a variety of human immune functions, such as reducing the level of airway inflammation that occurs following exposure to relevant triggers (e.g. exercise).
Imbalances and/or deficiencies in gut bacterial composition/metabolic activity have been identified in children/adults diagnosed asthma. However, the potential mechanisms behind prebiotic mediated improvements in the severity of asthma have yet to be investigated.
Participants with and without A/EIB will be allocated two separate nutritional supplements following a double-blind, placebo-controlled design. During the first phase of the nutritional intervention, participants will consume the first supplement (either prebiotic or placebo), for a total duration of four weeks. A two-week wash out period will then be completed before the remaining nutritional supplement is administered for an equal duration.
Analyses of key human/bacterial metabolite concentrations will be carried out alongside assessments of immune and pulmonary function, and intestinal permeability at baseline, and throughout all phases of the nutritional intervention. Current understandings of the role of the gut microbiota in the pathogenesis of A/EIB will be expanded through the investigation of novel pathophysiological mechanisms, helping to inform future therapeutic prospects for asthma.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||38 participants|
|Intervention Model:||Crossover Assignment|
|Intervention Model Description:||
Participants will be administered a prebiotic (galactooligosaccharide; HOST-DM059), and a taste/appearance matched placebo (Maltodextrin) in a, double-blind, placebo-controlled, crossover design.
The nutritional intervention will be completed over a twelve week period, consisting of two, four-week supplementation phases separated by a four-week wash out period. Participants will be randomly allocated one of the nutritional supplements during phase one (labelled as either 'L', or 'X'), and asked to consume one powdered sachet every morning (3.6g). Participants will then complete a four week wash out period, before being assigned the remaining nutritional supplement during phase two. Sachets can be reconstituted in tea/coffee/fruit juice, or sprinkled over cereal etc.
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
Only the company providing the nutritional supplements (HOST Therabiomics) will be aware of the supplement blinding protocol.
Upon trial completion (e.g. the final visit of the final participant), the chief investigator will contact HOST Therabiomics to obtain information on the supplement blinding protocol. Should any participants, care providers, investigators, or outcome assessors become aware of the blinding protocol during the trial they will be informed not to disclose this information to any other relevant personnel. Participants who become aware of the blinding protocol during participation would be withdrawn from the trial.
|Official Title:||The Effects of HOST-DM059 Prebiotic Supplementation on Gut Bacterial Metabolites, and Markers of Systemic Inflammation in Adults With and Without Hyperpnoea-Induced Bronchoconstriction: A Double-Blind, Placebo-Controlled, Crossover Trial.|
|Actual Study Start Date :||November 15, 2017|
|Estimated Primary Completion Date :||March 31, 2019|
|Estimated Study Completion Date :||May 31, 2019|
Experimental: HOST-DM059 (Prebiotic)
HOST-DM059 is the only Second Generation Prebiotic, manufactured by Clasado Biosciences/HOST Therabiomics. HOST-DM059 consists of a specific type of carbohydrate/dietary fibre (GOS), and an enzyme extracted from species of Bifidobacteria (e.g. The β-Galacotosidase Enzyme, & Bifidobacterium Bifidum). The enzyme from which HOST-DM059 is developed provides a highly selective source of energy for certain species of Bifidobacteria. HOST-DM059 encourages the growth and development of Bifidobacteria. Certain species of Bifidobacteria have been demonstrated to exert prominent immunomodulatory effects in terms of regulating systemic inflammation.
Dietary Supplement: HOST-DM059
Experimental Supplement: HOST-DM059.
Participants will be asked to orally consume one powdered sachet each day, at the same time in the morning, reconstituted in tea/coffee/fruit juice, or sprinkled over cereal etc. Whichever method of consumption is chosen, this must be kept consistent across both supplementation phases.
Other Name: Bimuno, B-GOS, Prebiotic, Galactooligosaccharide.
Placebo Comparator: Maltodextrin
Maltodextrin will be administered as a taste/appearance-matched sugar/carbohydrate.
Dietary Supplement: Maltodextrin
Placebo Comparator: Maltodextrin.
Other Name: Placebo
- Changes In Regulatory T Cell FOXP3 Expression From Baseline To Post Prebiotic Supplementation. [ Time Frame: Week 0, Week 4, Week 6, Week 10 (Collected At Rest). ]Flow Cytometric Analysis: CD4+ CD25+ IL-10+ Regulatory T Cell FOXP3 Expression (
- Change In Systemic Immune Function/Inflammatory Markers [ Time Frame: Week 0, Week 4, Week 6, Week 10 (Blood Sample Collected At Rest). ]Flow Cytometric Analysis: Interleukin (IL)-10, Hematopoietic Prostaglandin D Synthase Enzyme (Pathogenic Effector/Non-Pathogenic Effector TH2 Cells), CD3 (T Cells), CD25 (Regulatory T Cells), Transforming Growth Factor-Beta (TH2 Cells), Fork-Head Box Protein-3 (Regulatory T Cells), CD161 (PETH2 Cells), Interferon-Gamma (TH1 Cells), Live/Dead, Total & Specific White Blood Cell Counts (Eosinophils, Basophils, Neutrophils, Monocytes, Lymphocytes).
- Change In Pulmonary Function (FEV1) [ Time Frame: Week 0, Week 4, Week 6, Week 10 (At Rest & In Duplicate At 3, 6, 10, 15, 20, & 30 Minutes Post EVH). ]
% Drop In Pulmonary Function (FEV1) Post EVH = 100*(Highest Baseline FEV1-Lowest Post EVH FEV1)/Highest Baseline FEV1. Used To Objectively Diagnose Asthma/EIB (> 10% Drop In FEV1 Post EVH At Two Consecutive Time Points), And Classify Severity As Mild (> 10% - < 25% Drop In FEV1), Moderate (> 25% - < 50% Drop In FEV1), Or Severe (> 30%, Or 50% Drop In FEV1 For Patients Receiving/Not Receiving Steroid Based Treatments).
All Pulmonary Function Parameters: FEV1, FVC, PEF, FEF25%-75%.
> 10% Reduction = Positive Objective Diagnosis (Asthma/EIB).
- Change In The Asthma Control Questionnaire - Perceived Symptom Management [ Time Frame: Weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10. (Upon Experimental Trial Arrival During Weeks 0, 4, 6, & 10). ]Common Asthma Symptoms Management: Night Time Awakening, Upon Waking Symptom Severity, Physical Activity Limitation, Dyspnoea (Breathlessness), Wheezing, Reliever Medication Usage (Rating 0-6).
- Change In Urinary Metabolite Concentrations [ Time Frame: Week 0, Week 4, Week 6, Week 10 (Urine Sample) (Collected At Rest & 60 Minutes Post EVH). ]E.G.: Acetic Acid, Propionic Acid, I-Butyric Acid, N-Butyric Acid, I-Valeric Acid, N-Valeric Acid, N-Caproic Acid.
- Change In The Medication Adherence Report Scale For Asthma (MARS-A) [ Time Frame: Weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10. (Upon Experimental Trial Arrival During Weeks 0, 4, 6, & 10). ]Asthma Medication & Nutritional Interventions Adherence Measurement (12 Questions) (Rating 1-5).
- Change In 24 Hour Weighed Nutritional Intake Record [ Time Frame: Week 0, Week 4, Week 8, Week 12 (24 Hours Before Experimental Trial). ]Quantitative Measurement - Habitual Nutritional Consumption (Assess Nutritional Intake Consistency Across Experimental Trials).
- Changes In Intestinal Permeability Markers [ Time Frame: Week 0, Week 4, Week 6, Week 10 (Blood Sample Collected At Rest). ]Blood (Serum/Plasma) Based Measurement.
- Principal Component Analysis/Cluster Analysis - Primary/Secondary Outcome Measures [ Time Frame: Post Data Collection. ]All Relevant Meta-Data.
- Partial Least Squares Discriminant Analysis. [ Time Frame: Post Data Collection. ]
Urinary Metabolite Profiles.
1H Nuclear Magnetic Resonance (NMR) Spectroscopy.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02872675
|Contact: Paul A Lester, BSc (Hons)||07564329039||Paul.Lester2015@my.ntu.ac.uk|
|Contact: Graham R Sharpe, PhD||0115848 ext 3340||Graham.Sharpe@ntu.ac.uk|
|Nottingham Trent University||Recruiting|
|Nottingham, Nottinghamshire, United Kingdom, NG11 8NS|
|Contact: Paul A Lester, BSc (Hons) 07564329039 Paul.Lester2015@my.ntu.ac.uk|
|Contact: Graham R Sharpe, PhD 0115848 ext 3340 Graham.Sharpe@ntu.ac.uk|
|Principal Investigator: Paul A Lester, BSc (Hons)|
|Sub-Investigator: Graham R Sharpe, PhD|
|Sub-Investigator: Michael A Johnson, PhD|
|Sub-Investigator: Kirsty A Hunter, PhD|
|Sub-Investigator: Neil C Williams, PhD|
|Sub-Investigator: Robert Needham, MRes|
|Sub-Investigator: Mark Elliott, BSc|
|Sub-Investigator: Elijas Gricius, BSc|
|Sub-Investigator: Connor J Parker, BSc|
|Sub-Investigator: Talha Khan|
|Study Director:||Graham R Sharpe, PhD||Nottingham Trent University|