Gamma-Aminobutyric AcidNCT03835468
The Role of the Microbiota-gut-brain Axis in Brain Development and Mental Health
A study testing Galacto-oligosaccharides and Maltodextrin in people with Gamma-Aminobutyric Acid and Anxiety, run by University of Surrey at 1 site in United Kingdom.
Trial summary
The role of the microbiota-gut-brain axis in brain development and mental health Read more about this study
- Who is it for?
- Ages 18 to 25 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Gamma-Aminobutyric Acid, Anxiety, Glutamate
- What is being tested?
- Galacto-oligosaccharides and Maltodextrin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Feb 2019to Mar 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 25 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Females
- Aged between 18-25
Who cannot join
- Clinical levels of anxiety and/ or co-morbid diagnoses (e.g. depression)
- Current or previous neurological disorders
- Current or previous psychiatric disorders
- Current or previous gastrointestinal disorders
- Current or previous endocrine disorders
- Antibiotic use 3 months prior to the study
- Regular use of pre- and probiotics, including 3 months prior to the study
- Vegan diets
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
University of Surrey
Guildford, Surrey, GU2 7XH
Kathrin Cohen-Kadosh, Phd, 01483683968, k.cohenkadosh@surrey.ac.uk
Nicola Johnstone, Phd, nicola.johnstone@surrey.ac.uk
About this study
The role of the microbiota-gut-brain axis in brain development and mental health
Read the detailed description
Anxiety disorders are debilitating conditions that carry enormous individual, social and economic costs. For example, it has been estimated that lifelong persistent mental health problems cost the UK taxpayer £8.6 billion annually. Many mental health problems have their onset in the transitional period from adolescence to early adulthood, possibly a result of the complex and concurrent hormonal, genetic, brain maturational and social changes during this period. Research has shown that brain development and maturation extends well into the third decade of life and that brain activation patterns in late adolescence and early adulthood still differ significantly from mature adults. In the recent years, the microbiome has emerged as a new and important factor that may increase the mental health risk for an individual. The intestine and the brain are intimately connected via the gut-brain axis, which involves bidirectional communication via neural, endocrine and immune pathways. Research in both the human and animal models has also highlighted the important role that intestinal microbiota play in regulating the brain, subsequent behaviour, and particularly in anxiety-like behaviour. Most importantly, it has been shown that the period of adolescence may be a critical window during development where microbiota help fine-tune the gut-brain axis related to stress responses and anxiety.
The research proposed here will investigate the role of the microbiota-gut-brain axis in brain development and mental health. Specifically, the researchers will investigate the effect of prebiotic intake on mental health and well-being in late adolescence/early adulthood, with a particular focus on cortical excitability and connectivity in the emotion regulation brain network.
This research will extend previous research into gut-brain interactions into the final years of adolescence. The period of adolescence is not only important with regards to fine-tuning emotion regulation networks, but also, as has been shown in recent work, critical for establishing healthy gut-brain communication patterns. Specifically, here we will investigate how prebiotic intake (Galacto-oligosaccharides) for 4 weeks affects cognitive functioning, psychological well-being and the underlying brain networks in a sample of 120 female undergraduate students (aged 18-25 years). Specifically, the proposed research has two main aims:
- To investigate how prebiotic intake affects cortical excitability and plasticity, such as inhibitory GABA/ excitatory glutamate levels in key emotion regulation brain networks.
- To investigate how prebiotic intake affects psychological functioning and well-being, in particular with regards to anxiety and thought control abilities.
120 participants will be divided into two group of 60 participants, groups will be matched for age, handedness and socio-economic status. At each testing time (Time 1, 2 and 3), participants in both groups will undergo comprehensive behavioural and psychological testing to establish baseline measures of cognitive functioning and psychological well-being (such as anxiety levels).
Each participant will also be asked to collect a stool sample at home for 16s rRNA sequencing of the microbiome at both testing times. Group 1 will receive a daily dosage of GOS over 4 weeks, whereas group 2 will receive a placebo over the same period. In addition, participants from either group will also participate in a brain imaging session to assess the effect of prebiotic supplement intake on the functional responsiveness of emotion regulation brain networks.
For this study, The researchers predict that the intervention group will show improvements in behavioural and psychological variables related to emotion regulation and anxiety in comparison to the placebo group (Hypothesis 1). Predictions also expect to observe decreased excitability in core emotion regulation brain regions such as the amygdala and prefrontal cortex, as assessed via 1H-magnet resonance spectroscopy (Hypothesis 2).
- Being tested
- Galacto-oligosaccharides, Maltodextrin
- Medical subject headings
- Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Galacto-oligosaccharidesDietary supplement
Also called GOS
GOS is a form of prebiotic, which enhance the growth of beneficial gut bacteria
MaltodextrinDietary supplement
sugar based placebo
| Study group | Role | What they receive |
|---|---|---|
| Galacto-oligosaccharides (GOS) Group | Experimental | Participants in this group will receive the daily dosage of galacto-oligosaccharides (GOS) prebiotic for 4 weeks Receives: Dietary Supplement: Galacto-oligosaccharides |
| Maltodextrin Group | Placebo comparator | Participants in this group will receive the daily dosage of Maltodextrin placebo for 4 weeks Receives: Dietary Supplement: Maltodextrin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in brain indices of emotion regulation abilities as a function of prebiotic intake 1
Increase in brain-based metabolite concentrations (gamma-aminobutyric acid (GABA)) as assessed via Magnetic resonance spectroscopy in the prebiotics group in comparison to the placebo group.
Measured: 4 weeks of intervention
Changes in brain indices of emotion regulation abilities as a function of prebiotic intake 2
Increase in functional connectivity in brain networks supporting emotion regulation abilities (as assessed via functional magnetic resonance imaging) in the prebiotics group in comparison to the placebo group.
Measured: 4 weeks of intervention
Changes in psychological measures of emotion regulation abilities as a function of prebiotic intake 1
Decrease in Trait anxiety (State-Trait Anxiety Inventory, Spielberger, 1977) in the prebiotics group in comparison to the placebo group.. For this inventory, a lower overall score is the desired outcome.
Measured: 4 weeks of intervention
Changes in psychological measures of emotion regulation abilities as a function of prebiotic intake 2
Decrease in Social Anxiety for adolescents (Social Anxiety Scales, La Greca, 1999) in the prebiotics group in comparison to the placebo group. For this scale, a lower overall score is the desired outcome.
Measured: 4 weeks of intervention
Changes in psychological measures of emotion regulation abilities as a function of prebiotic intake 3
Increase in thought control ability (Thought control ability questionnaire, Luciano et al., 2005) in the prebiotics group in comparison to the placebo group.. For this questionnaire, a higher overall score is the desired outcome.
Measured: 4 weeks of intervention
Changes in gut microbiome composition as a function of prebiotic intake
Increase in beneficial gut bacteria (percentage) in the prebiotics group in comparison to the placebo group. Based on stool sample analyses and microbiome sequencing.
Measured: 4 weeks of intervention
Changes in gut microbiome composition as a function of prebiotic intake
Increase in diversity of gut bacteria in the prebiotics group (number of different bacteria) in comparison to the placebo group. Based on stool sample analyses and microbiome sequencing.
Measured: 4 weeks of intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2019
- Study start1 Feb 2019
- Primary completionMar 2022 (estimated)
- Study completionMar 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gamma-Aminobutyric AcidStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomly assigned into two groups. Group 1 will receive a daily dosage of GOS over 4 weeks, whereas group 2 will receive a placebo over the same period.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Surrey
- Sponsor type
- University, hospital or other
- Collaborators
- FrieslandCampina
- Responsible party
- Principal investigator, Katherin Cohen-Kadosh, University of Surrey
- Investigators
- Kathrin Cohen Kadosh, PhD, Principal investigator, University of Surrey
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03835468
- Sponsor's protocol ID
- PrebioticExtensionStudyGU2
- Status last verified
- Apr 2021
- First submitted
- 1 Feb 2019
- Last updated
- 29 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of the Microbiota-gut-brain Axis in Brain Development and Mental Health
- ClinicalTrials.gov ID
- NCT03835468
- Acronym / sponsor ID
- PrebioticExtensionStudyGU2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- University of SurreyUniversity, hospital or other
- Collaborators
- FrieslandCampina
- Study start
- 1 Feb 2019 (actual)
- Primary completion
- Mar 2022 (estimated)
- Study completion
- Mar 2023 (estimated)
- First posted
- 8 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The role of the microbiota-gut-brain axis in brain development and mental health
Detailed description
Anxiety disorders are debilitating conditions that carry enormous individual, social and economic costs. For example, it has been estimated that lifelong persistent mental health problems cost the UK taxpayer £8.6 billion annually. Many mental health problems have their onset in the transitional period from adolescence to early adulthood, possibly a result of the complex and concurrent hormonal, genetic, brain maturational and social changes during this period. Research has shown that brain development and maturation extends well into the third decade of life and that brain activation patterns in late adolescence and early adulthood still differ significantly from mature adults. In the recent years, the microbiome has emerged as a new and important factor that may increase the mental health risk for an individual. The intestine and the brain are intimately connected via the gut-brain axis, which involves bidirectional communication via neural, endocrine and immune pathways. Research in both the human and animal models has also highlighted the important role that intestinal microbiota play in regulating the brain, subsequent behaviour, and particularly in anxiety-like behaviour. Most importantly, it has been shown that the period of adolescence may be a critical window during development where microbiota help fine-tune the gut-brain axis related to stress responses and anxiety.
The research proposed here will investigate the role of the microbiota-gut-brain axis in brain development and mental health. Specifically, the researchers will investigate the effect of prebiotic intake on mental health and well-being in late adolescence/early adulthood, with a particular focus on cortical excitability and connectivity in the emotion regulation brain network.
This research will extend previous research into gut-brain interactions into the final years of adolescence. The period of adolescence is not only important with regards to fine-tuning emotion regulation networks, but also, as has been shown in recent work, critical for establishing healthy gut-brain communication patterns. Specifically, here we will investigate how prebiotic intake (Galacto-oligosaccharides) for 4 weeks affects cognitive functioning, psychological well-being and the underlying brain networks in a sample of 120 female undergraduate students (aged 18-25 years). Specifically, the proposed research has two main aims:
- To investigate how prebiotic intake affects cortical excitability and plasticity, such as inhibitory GABA/ excitatory glutamate levels in key emotion regulation brain networks.
- To investigate how prebiotic intake affects psychological functioning and well-being, in particular with regards to anxiety and thought control abilities.
120 participants will be divided into two group of 60 participants, groups will be matched for age, handedness and socio-economic status. At each testing time (Time 1, 2 and 3), participants in both groups will undergo comprehensive behavioural and psychological testing to establish baseline measures of cognitive functioning and psychological well-being (such as anxiety levels).
Each participant will also be asked to collect a stool sample at home for 16s rRNA sequencing of the microbiome at both testing times. Group 1 will receive a daily dosage of GOS over 4 weeks, whereas group 2 will receive a placebo over the same period. In addition, participants from either group will also participate in a brain imaging session to assess the effect of prebiotic supplement intake on the functional responsiveness of emotion regulation brain networks.
For this study, The researchers predict that the intervention group will show improvements in behavioural and psychological variables related to emotion regulation and anxiety in comparison to the placebo group (Hypothesis 1). Predictions also expect to observe decreased excitability in core emotion regulation brain regions such as the amygdala and prefrontal cortex, as assessed via 1H-magnet resonance spectroscopy (Hypothesis 2).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Participants will be randomly assigned into two groups. Group 1 will receive a daily dosage of GOS over 4 weeks, whereas group 2 will receive a placebo over the same period.
| Arm | Type | Receives |
|---|---|---|
| Galacto-oligosaccharides (GOS) Group | Experimental | Dietary Supplement: Galacto-oligosaccharidesParticipants in this group will receive the daily dosage of galacto-oligosaccharides (GOS) prebiotic for 4 weeks |
| Maltodextrin Group | Placebo comparator | Dietary Supplement: MaltodextrinParticipants in this group will receive the daily dosage of Maltodextrin placebo for 4 weeks |
Who may qualify
- Ages
- 18 to 25 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Females
- Aged between 18-25
Key exclusion criteria (8 listed)
- Clinical levels of anxiety and/ or co-morbid diagnoses (e.g. depression)
- Current or previous neurological disorders
- Current or previous psychiatric disorders
- Current or previous gastrointestinal disorders
- Current or previous endocrine disorders
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Galacto-oligosaccharidesAlso: GOSGOS is a form of prebiotic, which enhance the growth of beneficial gut bacteria | Dietary supplement | Galacto-oligosaccharides (GOS) Group |
| Maltodextrinsugar based placebo | Dietary supplement | Maltodextrin Group |
Primary outcome
Changes in brain indices of emotion regulation abilities as a function of prebiotic intake 1
Time frame: 4 weeks of intervention
Increase in brain-based metabolite concentrations (gamma-aminobutyric acid (GABA)) as assessed via Magnetic resonance spectroscopy in the prebiotics group in comparison to the placebo group.
Changes in brain indices of emotion regulation abilities as a function of prebiotic intake 2
Time frame: 4 weeks of intervention
Increase in functional connectivity in brain networks supporting emotion regulation abilities (as assessed via functional magnetic resonance imaging) in the prebiotics group in comparison to the placebo group.
Changes in psychological measures of emotion regulation abilities as a function of prebiotic intake 1
Time frame: 4 weeks of intervention
Decrease in Trait anxiety (State-Trait Anxiety Inventory, Spielberger, 1977) in the prebiotics group in comparison to the placebo group.. For this inventory, a lower overall score is the desired outcome.
Changes in psychological measures of emotion regulation abilities as a function of prebiotic intake 2
Time frame: 4 weeks of intervention
Decrease in Social Anxiety for adolescents (Social Anxiety Scales, La Greca, 1999) in the prebiotics group in comparison to the placebo group. For this scale, a lower overall score is the desired outcome.
Changes in psychological measures of emotion regulation abilities as a function of prebiotic intake 3
Time frame: 4 weeks of intervention
Increase in thought control ability (Thought control ability questionnaire, Luciano et al., 2005) in the prebiotics group in comparison to the placebo group.. For this questionnaire, a higher overall score is the desired outcome.
Changes in gut microbiome composition as a function of prebiotic intake
Time frame: 4 weeks of intervention
Increase in beneficial gut bacteria (percentage) in the prebiotics group in comparison to the placebo group. Based on stool sample analyses and microbiome sequencing.
Changes in gut microbiome composition as a function of prebiotic intake
Time frame: 4 weeks of intervention
Increase in diversity of gut bacteria in the prebiotics group (number of different bacteria) in comparison to the placebo group. Based on stool sample analyses and microbiome sequencing.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kathrin Cohen Kadosh, PhD principal investigator
University of Surrey
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Galacto-oligosaccharides and Maltodextrin in people with Gamma-Aminobutyric Acid and Anxiety, run by University of Surrey at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kathrin Cohen Kadosh, PhD (01483 68 3968, k.cohenkadosh@surrey.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in brain indices of emotion regulation abilities as a function of prebiotic intake 1 (time frame: 4 weeks of intervention). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2021.