Gut-brain Axis, Brain Function, and Behaviour.

Does Stimulating Friendly Gut Bacteria Improve Brain Function and Behaviour?

The aim is to test if dietary supplementation with prebiotics reduces measures of anxiety in healthy human participants with high self-reported levels of anxiety. Study will test for an effect on behavioural, neuroendocrine and brain imaging markers of anxiety.

Study Overview

• Status: Unknown
• Conditions: Anxiety; Magnetic Resonance Imaging; Decision Making; Cortisol; Humans; Emotion; Prebiotics
• Intervention / Treatment: Dietary supplement: Prebiotics; Dietary supplement: Maltodextrin (placebo)

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 9DU
      • Recruiting
      • University of Oxford
      • Contact: University o Oxford; Phone Number: 07438239953; Email: gershon.spitz@ndcn.ox.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Trait anxiety levels > 40 on STAI trait inventory
• Participant is willing and able to give informed consent for participation in the study
• Not currently taking any psychoactive medications

Exclusion Criteria:

• Pregnant participants
• No contraindications to prebiotic administration
• Antibiotic, probiotics and/or prebiotic treatment in at least the two previous months.
• Participants who are taking any other food supplements that, in the opinion of the Investigators, may affect the results.
• Participants who are taking any medications that, in the opinion of the Investigators, may affect the results.
• Any significant change in diet which, at the discretion of the Investigators, may affect the results.
• Participants who have recently participated in another research trial which, at the discretion of the Investigators, may affect the results.
• A history of dementia, traumatic brain injury or stroke.
• Anyone who is unable to perform the behavioural tasks.
• Current use of any psychoactive medication.
• Current use of psychological treatment.
• Anyone who does not have adequate understanding of English, sufficient to give informed consent.
• Any person who has a history of drug abuse or a previous history of a neurological, or has a history of neurosurgical procedure is excluded as they may be at increased risk of epilepsy and data collected may be influenced by their condition.
• Anyone with any metal implants or implantable device would be excluded from any brain imaging studies as indicated by the MRI safety screening form.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Start with prebiotics; Half of the participants start with prebiotics, followed by a testing period. After a wash-out period they will continue with placebo followed by a testing period.	Dietary supplement: Prebiotics; Galactooligosaccharides (GOS) (prebiotics) will be consumed by the participants for 4-6 weeks
EXPERIMENTAL: Start with placebo; Half of the participants start with placebo, followed by a testing period. After a wash-out period they will continue with prebiotics followed by a testing period.	Dietary supplement: Maltodextrin (placebo); Maltodextrin (placebo) will be consumed by the participants for 4-6 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cortisol awakening response (CAR)	CAR, a marker of stress responsivity, should be decreased after taking prebiotics compared to placebo (as previously found in non-anxious participants in Schmidt et al., 2015, Psychopharmacology)	Cortisol awakening responses will be measured at the end of the first intervention phase (4-6 weeks after study entry) and at the end of the second intervention phase (11-15 weeks post study entry).
Brain imaging (BOLD fMRI activity) in amygdala and cortical regions	Brain imaging (BOLD fMRI activity) in amygdala and cortical regions Will provide neural measures of threat reactivity. We predict decreased amygdala and/or increased parietal-prefrontal brain activity after prebiotics compared to placebo, indicating an anxiolytic-like profile (fearful -neutral face trials in the low load condition) (as in Bishop et al, 2007 and Ironside et al, 2017)	Brain imaging will be measured at the end of the first intervention phase (4-6 weeks after study entry) and at the end of the second intervention phase (11-15 weeks post study entry).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in gut microbiome	Availability of specific bacteria in microbiome will change as function of prebiotics and not during placebo. The change will be measured at the start of each intervention compared to the end of each intervention	Changes in the microbiome will be measure using a single stool/faecal sample at four time points: baseline (0 weeks), following first intervention (4-6 weeks), following washout (7-9 weeks), and following the second intervention (11-15 weeks).

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: National Health and Medical Research Council, Australia; Monash University; Oxford Health Biomedical Research Centre (OH BRC) support scheme; Wellcome Centre for Integrative Neuroimaging

Publications and helpful links

General Publications

• Schmidt K, Cowen PJ, Harmer CJ, Tzortzis G, Errington S, Burnet PW. Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers. Psychopharmacology (Berl). 2015 May;232(10):1793-801. doi: 10.1007/s00213-014-3810-0. Epub 2014 Dec 3.
• Bishop SJ, Jenkins R, Lawrence AD. Neural processing of fearful faces: effects of anxiety are gated by perceptual capacity limitations. Cereb Cortex. 2007 Jul;17(7):1595-603. doi: 10.1093/cercor/bhl070. Epub 2006 Sep 6.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 6, 2018
• Primary Completion (ANTICIPATED): December 1, 2019
• Study Completion (ANTICIPATED): December 1, 2019

Study Registration Dates

• First Submitted: May 9, 2018
• First Submitted That Met QC Criteria: June 11, 2018
• First Posted (ACTUAL): June 13, 2018

Study Record Updates

• Last Update Posted (ACTUAL): June 13, 2018
• Last Update Submitted That Met QC Criteria: June 11, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: R52324_RE001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The study staff will ensure that the participants' data are safeguarded. The study will comply with the Data Protection Act, which requires personal data to be anonymised as soon as it is practical to do so. Students and collaborators may be given access to fully anonymized data under the supervision of the named investigators. Some peer-reviewed journals require submission of anonymised data that may also be uploaded to other data sharing initiatives. Access may be given to responsible members of the University of Oxford for the purposes of monitoring or audit. The participants' consent will be sought if this is to occur.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No