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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
Sponsor:
Collaborators:
University of Reading
Clasado Biosciences
Imperial College London
HOST Therabiomics
The John van Geest Cancer Research Centre
Information provided by (Responsible Party):
Paul Lester, Nottingham Trent University

Brief Summary:
The current study aims to explore the role of prebiotic supplementation in adults with and without Asthma/Exercise-Induced Bronchoconstriction (A/EIB). All participants will be asked to consume a prebiotic supplement, and a placebo, each for a total duration of four weeks, separated by a two-week wash out period. The investigators hypothesise that improvements in pulmonary function observed in adults with Asthma following prebiotic supplementation. We hypothesise that improvements in pulmonary function will be attributed, at least in part, to gut microbiota mediated improvements in human immune function.

Condition or disease Intervention/treatment Phase
Exercised Induced Asthma Asthma Dietary Supplement: HOST-DM059 Dietary Supplement: Maltodextrin Not Applicable

Detailed Description:

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 38 participants
Allocation: Non-Randomized
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)
Masking Description:

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.

Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
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




Primary Outcome Measures :
  1. 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 (


Secondary Outcome Measures :
  1. 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).

  2. 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).


  3. 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).

  4. 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.

  5. 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).

  6. 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).

  7. 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.


Other Outcome Measures:
  1. Principal Component Analysis/Cluster Analysis - Primary/Secondary Outcome Measures [ Time Frame: Post Data Collection. ]
    All Relevant Meta-Data.

  2. Partial Least Squares Discriminant Analysis. [ Time Frame: Post Data Collection. ]

    Urinary Metabolite Profiles.

    Untargetted Metabolomics.

    1H Nuclear Magnetic Resonance (NMR) Spectroscopy.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Be 18-50 years of age at the date of your first visit.

Have a body mass index (BMI) of 18.5-25 kg∙m2 (this will be worked out by the researchers using the participant's height and body weight).

Be physically active (completing 3 or more exercise sessions a week lasting at least 45 minutes each).

Be a non-smoker.

Asthma is defined as Steps 1, 2, or 3 based on British Thoracic Society guidelines.

Asthma sufferers must have a current medication prescription from their GP (e.g. maintenance/reliever inhalers).

In the researcher's opinion, the participant is able and willing to follow all trial requirements.

Exclusion Criteria

Asthma defined as Steps 4 or 5 based on British Thoracic Society guidelines.

Asthma sufferers who do not have a current medication prescription from their GP (e.g. maintenance and reliever inhalers).

Regular consumption of Omega-3 supplements, and/or high levels of Omega-3 intake from food (e.g. consuming more than 1-2 portions of oily fish such as salmon or mackerel a week).

Regularly consume antioxidant supplements.

Standard multivitamin and mineral supplements are acceptable, as long as the product label states the recommended Dietary Reference Values (DRV's).

If a single antioxidant supplement (e.g. Vitamin C), exceeds the recommended daily DRV's this will be checked with the chief investigator.

Take a daily dose of aspirin or other non-steroidal anti-inflammatory drugs such as ibuprofen.

Have consumed prebiotics and/or probiotics, drugs that affect gastrointestinal mobility, or laxatives in the 4 weeks before participation.

Currently taking a daily dose of anti-histamine, which could not be refrained from for 72 hours before each testing session.

Unable to refrain from taking Asthma medication (e.g. maintenance and reliever inhalers) for a prescribed duration before each testing session (e.g. 8-96 hours).

Vegetarian or vegan diet.

Previously diagnosed with chronic obstructive pulmonary disease (COPD), emphysema, chronic bronchitis, or similar respiratory illness.

Participants with asthma that have ever been hospitalised due to asthma (e.g. intensive care unit).

Participants with asthma that have received treatment with oral corticosteroids/been admitted to hospital during the past 12 months for their asthma.

An increase/step-up in asthma medication during the study (e.g. moving from Step 1 to Step 2, Step 2 to Step 3 etc.).

Participants with asthma who do not obtain an additional prescription for a reliever inhaler to be stored securely at NTU if needed during visits. Additional prescriptions must be obtained before familiarisation/visit two. Participants will be reimbursed for the cost of additional reliever inhaler prescriptions.

History of heart failure, pulmonary hypertension, embolism, or other pulmonary heart disease.

History of recurrent chest infections.

Smoker.

Pregnant, planning pregnancy or lactating.

Had an acute infection in the last four weeks, and/or major operation in the past four months.

History of gastrointestinal drug reaction.

Have taken antibiotics in the past 3 months.

History or current evidence of gastrointestinal disease (e.g. chronic constipation, diarrhoea, irritable bowel syndrome, Chrohn's disease).

Have recently taken part in other research projects. Participants will be asked to notify the chief investigator.

Participants are, or believe that they are lactose intolerant.


Information from the National Library of Medicine

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


Contacts
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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

Locations
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United Kingdom
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         
Sponsors and Collaborators
Nottingham Trent University
University of Reading
Clasado Biosciences
Imperial College London
HOST Therabiomics
The John van Geest Cancer Research Centre
Investigators
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Study Director: Graham R Sharpe, PhD Nottingham Trent University

Publications:

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Responsible Party: Paul Lester, PhD Student, Principal Investigator, Nottingham Trent University
ClinicalTrials.gov Identifier: NCT02872675     History of Changes
Other Study ID Numbers: 233556
First Posted: August 19, 2016    Key Record Dates
Last Update Posted: March 19, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Individual participant data may be made available to other researchers following completion of the current trial in an anonymised/pseudonymised format to prevent individual participant identification. Data will be provided in response to certain requests (e.g. if a systematic review and meta-analysis/statistical power calculation is being conducted that requires access to certain raw data).

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Paul Lester, Nottingham Trent University:
Asthma
Exercise-Induced Asthma
Gut Bacteria
Bimuno® Galactooligosaccharide
Pulmonary Function
Prebiotics
Exercise-Induced Bronchoconstriction
Gut Microbiota
Nutritional Intervention
Eucapnic Voluntary Hyperpnoea
Systemic Inflammation
Systemic Immune Function
Regulatory T Cells
TH1 Cells
TH2 Cells
Short-Chain Fatty Acids
Acetate
Propionate
Butyrate
Metabolomics
Airway Inflammation
Intestinal Permeability
Additional relevant MeSH terms:
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Asthma
Asthma, Exercise-Induced
Inflammation
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Pathologic Processes