The development of effective clinical trials is essential when exploring the link between the gut microbiome and the brain; for example, when looking at the potential of microbiome-based products to impact stress levels, focus or even exercise performance.
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This article looks at a number of considerations that will impact the design and delivery of these trials, from the design stage to delivery and the trial’s agreed endpoint.
Clinical trial design considerations
Improving research protocols in the area of gut-brain access is key to defining robust trials that effectively demonstrate and verify product efficacy. This is also vital when looking to make a regulatory claim for approval by the FDA or an equivalent organization.
Key aspects of the clinical trial design include defining the study population and determining which assessment tools should be used to measure the trial’s outcomes. The duration of the trial is also important.
Defining a study population involves determining whether to include and exclude criteria for participants, for example, deciding whether to study a healthy population or a population with a specific condition or symptom.
When defining an ideal population, it is important to consider the practicality and achievability of recruitment. A population must exist and must be accessible enough to be able to realistically recruit.
The population’s realistic ability to adhere to the protocol should also be considered. Restrictions around factors such as medication use are important in gut research, particularly antibiotic use, which may significantly impact the microbiome.
When these requirements are too strict, participants’ ability to adhere to the protocol may be impacted, and they are effectively set up to fail or at least deviate from the protocol.
This is also important in terms of making regulatory claims at the end of a research journey. A product must be proven to function in the general population where individuals are unlikely to strictly adhere to dosage requirements and may be taking a number of other products simultaneously.
Inclusion and exclusion criteria should be kept to a minimum and only include criteria that are essential to the study in question.
Choosing the right assessment tools
There is a virtually endless list of potential tools and metrics which can be used when looking to measure a product’s impact on gut-brain access.
Many factors impact gut health and the microbiome, and vice versa. Whether a research study is looking at how a probiotic improves exercise outcomes or stress levels or how antibiotics impact the gut microbiome, there are many opportunities for research in this area.
Central to making the most of these possibilities is the appropriate and careful selection of cognitive assessment tools.
It is important to consider the appropriate population being investigated; for example, some assessment tools are designed specifically for children, some specifically for adults, but not adults over 65.
The choice of cognitive assessment tool should be appropriate for the outcome of the study, for example, whether this is into stress, mood, cognition or sleep. The tool must be able to capture the type of change the study is looking to confirm, such as impairment on memory, stress levels or ability to focus on complex tasks.
These tools should ideally be able to capture clear, quantitative results and be accessible and appropriate to the population. It is often easier to capture a dramatic change in response to a product, particularly when it may alleviate a specific symptom, but this can be challenging if the change is more subtle.
For example, looking to demonstrate that a probiotic product shows a mild cognitive improvement in a healthy adult requires a very sensitive, specific tool that measures changes in reaction time; for example, a cognitive demand battery or a COMPASS test.
Optimizing trial duration
There are a number of considerations when selecting the length of clinical trials – this is particularly the case for trials involving cognitive, sleep or stress studies where results may be impacted by the circumstances of the trial itself.
One of the predominant deciding factors in trial length is often cost. While a shorter trial may be less expensive than a lengthy trial in the short term, it is possible that there are only inconclusive results at the end of that month-long trial, prompting the need to extend the trial further.
Trial duration considerations are also dependent on the requirements of the tools that are being used. It is also important to note that in order to be able to effectively compare a trial to previous studies or existing literature, the trial should use similar tools and be of similar duration to be comparable.
Clinicians will determine whether something is clinically meaningful or not based on the time that the changes are in effect. For example, a pain reduction score of two over a 6-month period would be considered to be clinically meaningful, so a trial would need to be at least six months long to demonstrate this.
Finally, the sensitivity of instruments is important, particularly when considering changes that cannot be measured by physical assessments alone.
For example, improvements in cognition would not necessarily occur in larger leaps over a short timeframe; this would likely occur gradually over time, so a longer study would be required to demonstrate an overall significant change.
Summary
A number of considerations should be kept in mind throughout the design, delivery, and analysis of the impact of microbiome-based products, particularly when these are seeking to establish a tangible and measurable impact of functions such as mood, sleep, and stress levels or cognition.
One of the best ways of ensuring that these trials are designed, delivered and analyzed effectively – and that they provide good, usable and reproducible results – is to work with an established external provider.
Atlantia Clinical Trials has over 10 years of experience in the provision of human clinical studies, with extensive expertise in study design, tool and assessment selection and data analysis.
About Atlantia Clinical Trials
Atlantia Clinical Trials Ltd is a CRO that specializes in conducting studies in foods, beverages and supplements for companies world-wide that want to scientifically validate their functional ingredients to support an: EFSA (European Food Safety Authority) Health Claim; FDA (Food & Drug Administration) Structure Function Claim; or General Product Marketing Claim.
Atlantia works with world leading scientists (among the top cited 1% internationally, in the areas of digestive health and functional foods) at the: APC Microbiome Institute in University College Cork, Ireland; Teagasc, Moorepark, Ireland and recognized centers of excellence globally.
Atlantia runs and operates its own clinic sites and conducts all studies to ICH-GCP standard (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use – Good Clinical Practice). Its team includes physician experts in digestive health, mental health (psychological stress and cognition), cardiovascular health, sports performance, metabolic disease, bone health, immune health and healthy ageing. The clinical team also includes project managers, research nurses, nutritionists, certified sports trainers and lab researchers.
Atlantia manages all elements from protocol design, placebo manufacture, recruitment, and study execution, to sample and data analysis, statistics and report/dossier preparation to provide a service which is technically, scientifically and clinically superior.
The clinical studies cover a broad spectrum of functional food and beverage categories, such as dairy, cereal, probiotic, different protein forms, infant-specific foods, vitamins/minerals, plant or marine extracts and medical foods.
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