Clinical trial NCT02872675: The Effects of Prebiotics on Gut Bacterial Parameters, Immune Function & Exercise-Induced Airway Inflammation.
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Exercised Induced Asthma
Asthma
Keywords: 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
Lead sponsor: Nottingham Trent University
Sponsor class: OTHER
Collaborators: name: University of Reading
name: Clasado Biosciences
name: Imperial College London
name: HOST Therabiomics
name: The John van Geest Cancer Research Centre
First posted: 2016-08-19
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
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.
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Changes In Regulatory T Cell FOXP3 Expression From Baseline To Post Prebiotic Supplementation.
timeFrame: Week 0, Week 4, Week 6, Week 10 (Collected At Rest).
Secondary outcomes:
measure: Change In Systemic Immune Function/Inflammatory Markers
timeFrame: Week 0, Week 4, Week 6, Week 10 (Blood Sample Collected At Rest).
measure: Change In Pulmonary Function (FEV1)
timeFrame: Week 0, Week 4, Week 6, Week 10 (At Rest & In Duplicate At 3, 6, 10, 15, 20, & 30 Minutes Post EVH).
measure: Change In The Asthma Control Questionnaire - Perceived Symptom Management
timeFrame: Weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10. (Upon Experimental Trial Arrival During Weeks 0, 4, 6, & 10).
measure: Change In Urinary Metabolite Concentrations
timeFrame: Week 0, Week 4, Week 6, Week 10 (Urine Sample) (Collected At Rest & 60 Minutes Post EVH).
measure: Change In The Medication Adherence Report Scale For Asthma (MARS-A)
timeFrame: Weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10. (Upon Experimental Trial Arrival During Weeks 0, 4, 6, & 10).
measure: Change In 24 Hour Weighed Nutritional Intake Record
timeFrame: Week 0, Week 4, Week 8, Week 12 (24 Hours Before Experimental Trial).
measure: Changes In Intestinal Permeability Markers
timeFrame: Week 0, Week 4, Week 6, Week 10 (Blood Sample Collected At Rest).
Other outcomes:
measure: Principal Component Analysis/Cluster Analysis - Primary/Secondary Outcome Measures
timeFrame: Post Data Collection.
measure: Partial Least Squares Discriminant Analysis.
timeFrame: Post Data Collection.
Locations:
city: Nottingham
country: United Kingdom
facility: Nottingham Trent University
state: Nottinghamshire
Study officials:
affiliation: Nottingham Trent University
name: Graham R Sharpe, PhD
role: STUDY_DIRECTOR
References:
citation: Williams NC, Johnson MA, Hunter KA, Sharpe GR. Reproducibility of the bronchoconstrictive response to eucapnic voluntary hyperpnoea. Respir Med. 2015 Oct;109(10):1262-7. doi: 10.1016/j.rmed.2015.08.006. Epub 2015 Aug 13.
citation: Vulevic J, Juric A, Walton GE, Claus SP, Tzortzis G, Toward RE, Gibson GR. Influence of galacto-oligosaccharide mixture (B-GOS) on gut microbiota, immune parameters and metabonomics in elderly persons. Br J Nutr. 2015 Aug 28;114(4):586-95. doi: 10.1017/S0007114515001889. Epub 2015 Jul 28.
citation: Williams NC, Johnson MA, Shaw DE, Spendlove I, Vulevic J, Sharpe GR, Hunter KA. A prebiotic galactooligosaccharide mixture reduces severity of hyperpnoea-induced bronchoconstriction and markers of airway inflammation. Br J Nutr. 2016 Sep;116(5):798-804. doi: 10.1017/S0007114516002762.
citation: Hevia A, Milani C, Lopez P, Donado CD, Cuervo A, Gonzalez S, Suarez A, Turroni F, Gueimonde M, Ventura M, Sanchez B, Margolles A. Allergic Patients with Long-Term Asthma Display Low Levels of Bifidobacterium adolescentis. PLoS One. 2016 Feb 3;11(2):e0147809. doi: 10.1371/journal.pone.0147809. eCollection 2016.
citation: Arrieta MC, Stiemsma LT, Dimitriu PA, Thorson L, Russell S, Yurist-Doutsch S, Kuzeljevic B, Gold MJ, Britton HM, Lefebvre DL, Subbarao P, Mandhane P, Becker A, McNagny KM, Sears MR, Kollmann T; CHILD Study Investigators; Mohn WW, Turvey SE, Finlay BB. Early infancy microbial and metabolic alterations affect risk of childhood asthma. Sci Transl Med. 2015 Sep 30;7(307):307ra152. doi: 10.1126/scitranslmed.aab2271.