Probiotic Impact on Cognitive Performance, and Metabolic Outcomes in Overweight Young Adults With Impaired Glucose Regulation

Not Applicable

Not yet recruiting

• Conditions: Impaired Glucose Regulation; Impaired Glucose Tolerance (Prediabetes); Prediabetes (Insulin Resistance, Impaired Glucose Tolerance); Overweight (BMI > 25); Cognitive Dysfunction; Neurovascular Coupling Mechanism and Cognitive Function

• Registration Number: NCT07073781
• Lead Sponsor: Leeds Beckett University

Brief Summary

This 12-week, double-blind, placebo-controlled trial will examine whether daily supplementation with the Lab4P probiotic can improve cognitive performance and metabolic health in overweight adults aged 18 to 35 with impaired glucose tolerance, a preclinical condition where blood glucose regulation is mildly disrupted. Seventy participants will be randomly assigned to receive either Lab4P or a placebo. The study will assess changes in memory, executive function, and processing speed, along with blood glucose control, cardiovascular function, cholesterol levels, body composition, and markers of inflammation. The study will also analyse changes in the gut microbiome and evaluate the safety and tolerability of the probiotic.

Detailed Description

Global rates of Overweight and obesity are rising at unprecedented levels, contributing to increased metabolic disturbances such as impaired glucose metabolism. Disruptions in glucose regulation are both characteristic of and contributory to the pathogenesis of metabolic disorders, including type 2 diabetes (T2D). Clinical perturbations in glucose homeostasis are strongly associated with cognitive impairments, and an increased risk of neurodegenerative diseases (Nazaribadie et al., 2014; Zilliox et al., 2016). Increasing evidence suggests that even slightly impaired glucose metabolism (IGM) may contribute to cognitive decline (Kirvalidze et al., 2022).

Emerging evidence shows that cognitive impairments, including memory, executive function, and visuomotor deficits, can be observed in young adults with impaired glucose metabolism, alongside early markers of structural and functional brain changes (Lamport et al., 2009; Repple et al., 2019). Neuroimaging studies have revealed reduced white matter integrity and decreased cerebral glucose metabolism in prediabetic individuals aged 22-35, particularly in brain regions associated with attention, self-regulation, and working memory (Repple et al., 2019; Ribeiro et al., 2023; Sadler et al., 2019; Deery et al., 2024a).

These neurocognitive effects appear to be driven by early neurovascular unit (NVU) dysfunction, involving elevated blood glucose, insulin resistance (IR), endothelial damage, and inflammation. Exaggerated glucose excursions promote oxidative stress and impair endothelial function at the blood brain barrier, disrupting cerebral blood flow (CBF), glucose transport and metabolic homeostasis (Di Pino et al., 2019; Kullmann et al., 2016; Feng \& Gao, 2024). Functional uncoupling between CBF and regional cerebral glucose metabolism has been directly observed in young adults with IR (Deery et al., 2024b).

Together, these findings suggest that NVU dysfunction may underlie early cognitive decline in young adults with IGM, and that this population represents a critical target for early, non-pharmacological intervention. Probiotic formulations, including the probiotic consortium Lab4P, have shown promise in improving metabolic markers and reducing inflammation, with preclinical data suggesting potential cognitive and neuroprotective benefits (Michael et al., 2021; Webberley et al., 2023). However, its procognitive effects in humans remain unexplored.

This trial will evaluate whether Lab4P supplementation can enhance cognitive performance, and cardiometabolic regulation in overweight young adults with IGM. By targeting a modifiable risk state early in life, the study aims to determine whether probiotic supplementation can serve as a viable strategy to mitigate long term neurocognitive and metabolic decline.

Study Timeline

• Status Verified: 2025-07
• Study First Submitted: 2025-07-09
• Study First Submitted QC: 2025-07-09
• Last Update Submitted: 2025-07-09
• Study First Posted: 2025-07-18
• Last Update Posted: 2025-07-18
• Study Start: 2025-08-25
• Primary Completion: 2026-06-30
• Study Completion: 2026-08-20

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

Not provided

Exclusion Criteria

• Diagnosed diabetes (any type).
• Diagnosed sleep disorders.
• Fasting glucose >6.9 mmol/L during screening.
• History of bariatric surgery (e.g., gastric bypass, sleeve gastrectomy).
• Major surgery, significant illness, trauma, infection, or myocardial infarction within the past 6 weeks.
• Current use of medications affecting glucose metabolism or probiotics
• Pregnancy or actively trying to conceive
• Night shift work within the past month

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Verbal Memory Performance	Baseline to Week 12 (end of treatment).	Assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB) Verbal Recognition Memory task (VRM) a computerized word list recall task, which measures accuracy in recalling previously presented verbal stimuli to evaluate verbal memory function.

Secondary Outcome Measures

Name	Time	Method
Visual Episodic Memory	Baseline to Week 12 (end of treatment).	Measured using the Paired Associates Learning (PAL) task (CANTAB), which assesses the ability to remember the locations of visual patterns and form new associations.
Number of Participants Reporting One or More Adverse Events (AEs) or Serious Adverse Events (SAEs)	Baseline to Week 12 (end of treatment).	All adverse events (AEs) and serious adverse events (SAEs) will be monitored through participant self-reports and case report forms. Events will be categorized by severity and relatedness to the study product.
Visuospatial Working Memory	Baseline to Week 12 (end of treatment).	Measured using the Spatial Working Memory (SWM) task (CANTAB), which assesses the ability to temporarily retain and manipulate spatial information and use effective search strategies during problem-solving.
Executive function (Response Inhibition and Impulse Control)	Baseline to Week 12 (end of treatment).	Measured using the Stop Signal Task (SST) (CANTAB), which assesses the ability to inhibit a dominant or preplanned motor response when signaled.
Executive function (Cognitive Flexibility and Attentional Set-Shifting)	Baseline to Week 12 (end of treatment).	Measured using the Intra-Extra Dimensional Set Shift (IED) task (CANTAB), which assesses the ability to shift attention between different stimulus dimensions and adapt to changing rules. This evaluates cognitive flexibility and executive function.
Processing speed, Psychomotor Response, and Attention	Baseline to Week 12 (end of treatment).	Measured using the Five Choice Reaction Time (RTI) task (CANTAB), which assesses how quickly and accurately participants respond to visual stimuli.
Cerebrovascular Reactivity (CVR)	Baseline to Week 12 (end of treatment).	CVR reflects the ability of cerebral blood vessels to dilate or constrict in response to changes in carbon dioxide, indicating the health of the brain's vascular system. Measured via transcranial Doppler ultrasound of the middle cerebral artery in response to hypercapnia/hypocapnia challenge.
Flow-Mediated Dilation (FMD)	Baseline to Week 12 (end of treatment).	Measured using ultrasound imaging of the brachial artery before and after a period of blood flow restriction using a pressure cuff. The artery's ability to dilate in response to the return of blood flow (reactive hyperemia) reflects endothelial function, an early indicator of vascular health and cardiovascular risk.
Global Sleep Quality	Baseline to Week 12 (end of treatment).	Measured using the Pittsburgh Sleep Quality Index (PSQI) global score, a validated 19-item self-report instrument assessing subjective sleep quality over the past month.
Sleep Latency	Baseline to Week 12 (end of treatment).	Assessed as a PSQI subcomponent, defined as the self-reported time (in minutes) taken to fall asleep on most nights.
Sleep Duration	Baseline to Week 12 (end of treatment).	Assessed as a PSQI subcomponent, reflecting the average number of hours of sleep per night.
Sleep Efficiency	Baseline to Week 12 (end of treatment).	Calculated as a PSQI subcomponent, defined as the ratio of total sleep time to time spent in bed, expressed as a percentage.
Sleep Disturbances	Baseline to Week 12 (end of treatment).	Derived from PSQI items capturing the frequency of nocturnal awakenings and other sleep interruptions.
Sleep Medication Use	Baseline to Week 12 (end of treatment).	Based on PSQI responses indicating frequency of pharmacological sleep aid use over the past month.
Total Cholesterol	Baseline to Week 12 (end of treatment).	Measured from a fasting capillary blood sample using the Cholestech LDX Analyzer (Abbott). This test provides total blood cholesterol levels, which are used to assess cardiovascular risk.
Daytime dysfunction	Baseline to Week 12 (end of treatment).	Evaluated using PSQI items assessing difficulties staying awake during the day and maintaining enthusiasm for activities.
Glycated Haemoglobin (HbA1C)	Baseline to Week 12 (end of treatment).	HbA1c reflects average blood glucose levels over the previous 2 to 3 months and is used to assess long-term blood sugar control. Measured from capillary blood using the Afinion 2 Analyzer (Abbott).
Fasting Blood Glucose	Baseline to Week 12 (end of treatment).	This measure reflects short-term blood sugar levels and is used to assess baseline glucose regulation. Measured from capillary blood using an over-the-counter, CE-marked glucometer.
Glucose Tolerance (AUC)	Baseline to Week 12 (end of treatment).	Assessed via a 2-hour oral glucose tolerance test (OGTT), with capillary blood glucose measured at 0, 30, 60, and 120 minutes post-glucose ingestion. These values will be used to calculate the area under the curve (AUC), which reflects how effectively the body regulates blood glucose over time.
Systolic blood pressure	Baseline to Week 12 (end of treatment).	Measured using an automated oscillometric device (Omron). This measure reflects the pressure in the arteries when the heart contracts and is a key indicator of cardiovascular health.
Diastolic blood pressure	Baseline to Week 12 (end of treatment).	Measured using an automated oscillometric device (Omron). This measure reflects the pressure in the arteries when the heart is at rest between beats and is an important marker of vascular function and cardiovascular risk.
Low-Density Lipoprotein Cholesterol (LDL-C)	Baseline to Week 12 (end of treatment).	Measured from a fasting capillary blood sample using the Cholestech LDX Analyzer (Abbott). LDL-C contributes to plaque buildup in the arteries and is a key cardiovascular risk marker.
High-Density Lipoprotein Cholesterol (HDL-C)	Baseline to Week 12 (end of treatment).	Measured from a fasting capillary blood sample using the Cholestech LDX Analyzer (Abbott). HDL-C helps remove excess cholesterol from the bloodstream and is protective against heart disease.
Triglycerides	Baseline to Week 12 (end of treatment).	Measured from a fasting capillary blood sample using the Cholestech LDX Analyzer (Abbott). Triglycerides are a type of fat found in the blood and are used to assess metabolic health and cardiovascular risk.
Body Mass Index (BMI)	Baseline to Week 12 (end of treatment).	Calculated as weight in kilograms divided by height in meters squared (kg/m²). Weight is measured using a calibrated digital scale and height with a stadiometer. BMI is a gold standard measure used to classify underweight, normal weight, overweight, and obesity.
Waist-to-Hip Ratio	Baseline to Week 12 (end of treatment).	Calculated by dividing waist circumference by hip circumference. This ratio reflects fat distribution and is a marker of cardiometabolic risk.
Total Lean Mass	Baseline to Week 12 (end of treatment).	Measured in kilograms using dual-energy X-ray absorptiometry (DXA). This measure reflects the total weight of muscle and other non-fat, non-bone tissues in the body.
Total Fat Mass	Baseline to Week 12 (end of treatment).	Measured in kilograms using dual-energy X-ray absorptiometry (DXA). This reflects the total amount of fat tissue in the body.
Percent Body Fat	Baseline to Week 12 (end of treatment).	Calculated from DXA-derived fat mass as a percentage of total body mass. This measure is used to evaluate body composition and excess adiposity-related risk.
Interleukin-6 (IL-6)	Baseline to Week 12 (end of treatment).	Quantified from venous plasma samples using enzyme-linked immunosorbent assay (ELISA) kits. IL-6 is a pro-inflammatory cytokine associated with immune response and chronic inflammation.
Tumor Necrosis Factor-Alpha (TNF-α)	Baseline to Week 12 (end of treatment).	Measured from venous plasma samples using ELISA kits. TNF-α is a cytokine involved in systemic inflammation and plays a role in metabolic and vascular dysfunction.
Gut Microbiota Diversity	Baseline to Week 12 (end of treatment).	Assessed by 16S rRNA gene sequencing of DNA extracted from stool samples. Diversity will be measured using alpha diversity indices (e.g., Shannon Index), reflecting the richness and evenness of microbial communities.
Gut Microbiota Community Dispersion	Baseline to Week 12 (end of treatment).	Assessed using beta diversity metrics such as Bray-Curtis dissimilarity and principal coordinates analysis (PCoA). This reflects variability in microbial composition between participants and time points.
Relative Abundance of Microbial Taxa	Baseline to Week 12 (end of treatment).	Determined from 16S rRNA gene sequencing data by calculating the proportion of individual bacterial taxa present in stool samples. This measure assesses how specific microbial populations change over time.
Adherence Rate	Baseline to Week 12 (end of treatment).	Assessed by capsule counts at the Week 12 visit and participant self-reports. The number of capsules taken will be calculated as a percentage of the total expected capsules over the 12-week intervention period.
Physical Discomfort Symptoms	Baseline to Week 12 (end of treatment).	Assessed using a structured, self-administered questionnaire. Participants will indicate whether they experienced specific physical symptoms during the past 14 days, and on how many days each symptom occurred. Symptom categories include gastrointestinal (e.g., constipation, diarrhoea, bloating), systemic (e.g., sore throat, headache, muscle ache, cold symptoms), and medication or menstrual-related events (e.g., use of antibiotics, vaginal treatments, menstruation).

Trial Locations

Locations (1)

Leeds Beckett University; 🇬🇧 Leeds, Greater Manchester, United Kingdom