Impaired Glucose RegulationProCogNCT07073781
Probiotic Impact on Cognitive Performance, and Metabolic Outcomes in Overweight Young Adults With Impaired Glucose Regulation
A study testing Lab4p Probiotic Consortium in people with Impaired Glucose Regulation and Impaired Glucose Tolerance (Prediabetes), run by Leeds Beckett University at 1 site in United Kingdom.
Trial 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 40 with impaired glucose tolerance, a preclinical condition where blood glucose regulation is mildly disrupted. Read more about this study
- Who is it for?
- Ages 18 to 40 years
- Conditions the study is for
- Impaired Glucose Regulation, Impaired Glucose Tolerance (Prediabetes), Prediabetes (Insulin Resistance, Impaired Glucose Tolerance)
- What is being tested?
- Lab4p Probiotic Consortium
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 15 Aug 2025to 20 Aug 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 40 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Aged 18-40 years
- Body Mass Index (BMI) between 25.0 and 29.9 kg/m² (classified as overweight)
- In good general health (self-reported)
- Normal self-reported sleep patterns, with no history of diagnosed sleep disorders
- Willing and able to provide informed consent
- Able to comply with study procedures, including fasting and oral glucose tolerance testing
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
Leeds Beckett University
Leeds, Greater Manchester, LS1 3HE
Lewis F Hepburn, +447541333140, L.hepburn3449@student.leedsbeckett.ac.uk
Lewis F Hepburn
About this study
Official title: A Double-blind Placebo-controlled Exploratory Trial to Assess the Impact of Daily Lab4P Probiotic Supplementation on Cognitive Performance and Metabolic Regulation in Overweight Young Adults With Impaired Glucose Regulation
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 40 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.
Read the 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. Increasing evidence suggests that even slightly impaired glucose metabolism (IGM) may contribute to cognitive decline.
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. 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.
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. Functional uncoupling between CBF and regional cerebral glucose metabolism has been directly observed in young adults with IR.
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. 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.
- 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
- Being tested
- Lab4p Probiotic Consortium, Placebo
- Keywords
- Probiotic supplementation, Psychobiotic, Cognitive performance, Metabolic function, Impaired glucose tolerance, Gut-brain axis
- Medical subject headings
- Glucose Intolerance, Prediabetic State, Insulin Resistance, Overweight, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lab4p Probiotic ConsortiumDietary supplement
The investigational product in this study is Lab4P, a patented multi-strain probiotic consortium formulated as a food supplement and supplied in capsule form. Each daily dose contains a total of 5 × 10¹⁰ CFU of live bacteria, comprising five strains: Lactobacillus acidophilus CUL60 and CUL21, Lactobacillus plantarum CUL66, Bifidobacterium bifidum CUL20, and Bifidobacterium animalis subsp. lactis CUL34. In addition to probiotics, each capsule also contains three micronutrients at 100-200% of the recommended daily intake: Vitamin D (10 µg; 200%), Vitamin C (80 mg; 100%), and Zinc (10 mg; 100%).
Lab4P is a marketed, human-approved product manufactured by Cultech Ltd. (Port Talbot, UK) and is classified as a food supplement, available for purchase without prescription. Both the active product and placebo will be identically packaged to maintain blinding.
PlaceboOther
Placebo capsules are composed of microcrystalline cellulose, and are identical in appearance to the test product.
| Study group | Role | What they receive |
|---|---|---|
| Group receiving the Lab4P probiotic capsules | Experimental | Experimental group will consume oral dose of 50 billion Colony forming Units (CFU) once daily till delivery. Receives: Dietary Supplement: Lab4p Probiotic Consortium |
| Group receiving the identical, non-active placebo | Placebo comparator | Microcrystalline cellulose/d each, up till delivery Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Verbal Memory Performance
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.
Measured: Baseline to Week 12 (end of treatment).
Secondary outcomes (37)
Visual Episodic Memory
Measured using the Paired Associates Learning (PAL) task (CANTAB), which assesses the ability to remember the locations of visual patterns and form new associations.
Measured: Baseline to Week 12 (end of treatment).
Number of Participants Reporting One or More Adverse Events (AEs) or Serious Adverse Events (SAEs)
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.
Measured: Baseline to Week 12 (end of treatment).
Visuospatial Working Memory
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.
Measured: Baseline to Week 12 (end of treatment).
Executive function (Response Inhibition and Impulse Control)
Measured using the Stop Signal Task (SST) (CANTAB), which assesses the ability to inhibit a dominant or preplanned motor response when signaled.
Measured: Baseline to Week 12 (end of treatment).
Executive function (Cognitive Flexibility and Attentional Set-Shifting)
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.
Measured: Baseline to Week 12 (end of treatment).
Processing speed, Psychomotor Response, and Attention
Measured using the Five Choice Reaction Time (RTI) task (CANTAB), which assesses how quickly and accurately participants respond to visual stimuli.
Measured: Baseline to Week 12 (end of treatment).
Cerebrovascular Reactivity (CVR)
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.
Measured: Baseline to Week 12 (end of treatment).
Flow-Mediated Dilation (FMD)
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.
Measured: Baseline to Week 12 (end of treatment).
Global Sleep Quality
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.
Measured: Baseline to Week 12 (end of treatment).
Sleep Latency
Assessed as a PSQI subcomponent, defined as the self-reported time (in minutes) taken to fall asleep on most nights.
Measured: Baseline to Week 12 (end of treatment).
Sleep Duration
Assessed as a PSQI subcomponent, reflecting the average number of hours of sleep per night.
Measured: Baseline to Week 12 (end of treatment).
Sleep Efficiency
Calculated as a PSQI subcomponent, defined as the ratio of total sleep time to time spent in bed, expressed as a percentage.
Measured: Baseline to Week 12 (end of treatment).
Sleep Disturbances
Derived from PSQI items capturing the frequency of nocturnal awakenings and other sleep interruptions.
Measured: Baseline to Week 12 (end of treatment).
Sleep Medication Use
Based on PSQI responses indicating frequency of pharmacological sleep aid use over the past month.
Measured: Baseline to Week 12 (end of treatment).
Daytime dysfunction
Evaluated using PSQI items assessing difficulties staying awake during the day and maintaining enthusiasm for activities.
Measured: Baseline to Week 12 (end of treatment).
Glycated Haemoglobin (HbA1C)
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).
Measured: Baseline to Week 12 (end of treatment).
Fasting Blood Glucose
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.
Measured: Baseline to Week 12 (end of treatment).
Glucose Tolerance (AUC)
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.
Measured: Baseline to Week 12 (end of treatment).
Systolic blood pressure
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.
Measured: Baseline to Week 12 (end of treatment).
Diastolic blood pressure
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.
Measured: Baseline to Week 12 (end of treatment).
Total Cholesterol
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.
Measured: Baseline to Week 12 (end of treatment).
Low-Density Lipoprotein Cholesterol (LDL-C)
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.
Measured: Baseline to Week 12 (end of treatment).
High-Density Lipoprotein Cholesterol (HDL-C)
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.
Measured: Baseline to Week 12 (end of treatment).
Triglycerides
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.
Measured: Baseline to Week 12 (end of treatment).
Body Mass Index (BMI)
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.
Measured: Baseline to Week 12 (end of treatment).
Waist-to-Hip Ratio
Calculated by dividing waist circumference by hip circumference. This ratio reflects fat distribution and is a marker of cardiometabolic risk.
Measured: Baseline to Week 12 (end of treatment).
Total Lean Mass
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.
Measured: Baseline to Week 12 (end of treatment).
Total Fat Mass
Measured in kilograms using dual-energy X-ray absorptiometry (DXA). This reflects the total amount of fat tissue in the body.
Measured: Baseline to Week 12 (end of treatment).
Percent Body Fat
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.
Measured: Baseline to Week 12 (end of treatment).
Interleukin-6 (IL-6)
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.
Measured: Baseline to Week 12 (end of treatment).
Tumor Necrosis Factor-Alpha (TNF-α)
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.
Measured: Baseline to Week 12 (end of treatment).
Gut Microbiota Diversity
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.
Measured: Baseline to Week 12 (end of treatment).
Gut Microbiota Community Dispersion
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.
Measured: Baseline to Week 12 (end of treatment).
Relative Abundance of Microbial Taxa
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.
Measured: Baseline to Week 12 (end of treatment).
Adherence Rate
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.
Measured: Baseline to Week 12 (end of treatment).
Physical Discomfort Symptoms
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).
Measured: Baseline to Week 12 (end of treatment).
Circulating Markers of Platelet Activity
Circulating markers of platelet activity will be quantified from venous blood samples using validated biochemical assays. These markers reflect platelet activation status and provide an index of platelet function in response to the intervention.
Measured: Baseline, Week 6, and Week 12.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2025
- Study start15 Aug 2025
- Primary completion30 Jun 2027 (estimated)
- Study completion20 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Impaired Glucose RegulationStudies 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 to one of two parallel groups (Lab4P or placebo) and will receive their assigned intervention daily for 12 weeks. There will be no crossover between groups, and outcomes will be assessed at multiple time points across the intervention period.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leeds Beckett University
- Sponsor type
- University, hospital or other
- Collaborators
- Cultech Ltd
- Responsible party
- Principal investigator, Lewis Hepburn, Leeds Beckett University
- Investigators
- Lewis F Hepburn, Msc, Principal investigator, Leeds Beckett UniversityLauren Owen, PhD, Study chair, Leeds Beckett UniversitySteve Trangmar, PhD, Study chair, Leeds Beckett University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07073781
- Sponsor's protocol ID
- LBU-Lab4P-ProCogTrial-2025
- Other IDs
- i-NutriLife Hub PoC_R3_012
- Acronym
- ProCog
- Status last verified
- Sep 2026
- First submitted
- 9 Jul 2025
- Last updated
- 17 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified IPD collected during the trial will be shared. This includes outcome-level data related to cognitive performance, sleep quality, glucose regulation, lipid profiles, vascular function, inflammatory biomarkers, body composition, and gut microbiota composition.
Publications
Zilliox LA, Chadrasekaran K, Kwan JY, Russell JW. Diabetes and Cognitive Impairment. Curr Diab Rep. 2016 Sep;16(9):87. doi: 10.1007/s11892-016-0775-x.
PubMed 27491830Webberley TS, Bevan RJ, Kerry-Smith J, Dally J, Michael DR, Thomas S, Rees M, Morgan JE, Marchesi JR, Good MA, Plummer SF, Wang D, Hughes TR. Assessment of Lab4P Probiotic Effects on Cognition in 3xTg-AD Alzheimer's Disease Model Mice and the SH-SY5Y Neuronal Cell Line. Int J Mol Sci. 2023 Feb 28;24(5):4683. doi: 10.3390/ijms24054683.
PubMed 36902113Sadler JR, Shearrer GE, Burger KS. Alterations in ventral attention network connectivity in individuals with prediabetes. Nutr Neurosci. 2021 Feb;24(2):140-147. doi: 10.1080/1028415X.2019.1609646. Epub 2019 Apr 28.
PubMed 31030631Ribeiro M, Yordanova YN, Noblet V, Herbet G, Ricard D. White matter tracts and executive functions: a review of causal and correlation evidence. Brain. 2024 Feb 1;147(2):352-371. doi: 10.1093/brain/awad308.
PubMed 37703295Repple J, Karliczek G, Meinert S, Forster K, Grotegerd D, Goltermann J, Redlich R, Arolt V, Baune BT, Dannlowski U, Opel N. Variation of HbA1c affects cognition and white matter microstructure in healthy, young adults. Mol Psychiatry. 2021 Apr;26(4):1399-1408. doi: 10.1038/s41380-019-0504-3. Epub 2019 Aug 29.
PubMed 31467393Nazaribadie M, Amini M, Ahmadpanah M, Asgari K, Jamlipaghale S, Nazaribadie S. Executive functions and information processing in patients with type 2 diabetes in comparison to pre-diabetic patients. J Diabetes Metab Disord. 2014 Feb 4;13(1):27. doi: 10.1186/2251-6581-13-27.
PubMed 24495302Michael DR, Davies TS, Jack AA, Masetti G, Marchesi JR, Wang D, Mullish BH, Plummer SF. Daily supplementation with the Lab4P probiotic consortium induces significant weight loss in overweight adults. Sci Rep. 2021 Jan 6;11(1):5. doi: 10.1038/s41598-020-78285-3.
PubMed 33408364Lamport DJ, Lawton CL, Mansfield MW, Dye L. Impairments in glucose tolerance can have a negative impact on cognitive function: a systematic research review. Neurosci Biobehav Rev. 2009 Mar;33(3):394-413. doi: 10.1016/j.neubiorev.2008.10.008. Epub 2008 Nov 5.
PubMed 19026680Kullmann S, Heni M, Hallschmid M, Fritsche A, Preissl H, Haring HU. Brain Insulin Resistance at the Crossroads of Metabolic and Cognitive Disorders in Humans. Physiol Rev. 2016 Oct;96(4):1169-209. doi: 10.1152/physrev.00032.2015. Epub 2016 Aug 3.
PubMed 27489306Kirvalidze M, Hodkinson A, Storman D, Fairchild TJ, Bala MM, Beridze G, Zuriaga A, Brudasca NI, Brini S. The role of glucose in cognition, risk of dementia, and related biomarkers in individuals without type 2 diabetes mellitus or the metabolic syndrome: A systematic review of observational studies. Neurosci Biobehav Rev. 2022 Apr;135:104551. doi: 10.1016/j.neubiorev.2022.104551. Epub 2022 Jan 29.
PubMed 35104494Feng L, Gao L. The role of neurovascular coupling dysfunction in cognitive decline of diabetes patients. Front Neurosci. 2024 Mar 21;18:1375908. doi: 10.3389/fnins.2024.1375908. eCollection 2024.
PubMed 38576869Di Pino A, Urbano F, Scicali R, Di Mauro S, Filippello A, Scamporrino A, Piro S, Purrello F, Rabuazzo AM. 1 h Postload Glycemia Is Associated with Low Endogenous Secretory Receptor for Advanced Glycation End Product Levels and Early Markers of Cardiovascular Disease. Cells. 2019 Aug 16;8(8):910. doi: 10.3390/cells8080910.
PubMed 31426413Deery HA, Liang E, Di Paolo R, Voigt K, Murray G, Siddiqui MN, Egan GF, Moran C, Jamadar SD. The association of regional cerebral blood flow and glucose metabolism in normative ageing and insulin resistance. Sci Rep. 2024 Jun 25;14(1):14574. doi: 10.1038/s41598-024-65396-4.
PubMed 38914735Deery HA, Liang E, Di Paolo R, Voigt K, Murray G, Siddiqui MN, Egan GF, Moran C, Jamadar SD. Peripheral insulin resistance attenuates cerebral glucose metabolism and impairs working memory in healthy adults. NPJ Metab Health Dis. 2024 Aug 2;2(1):17. doi: 10.1038/s44324-024-00019-0.
PubMed 40604159
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind Placebo-controlled Exploratory Trial to Assess the Impact of Daily Lab4P Probiotic Supplementation on Cognitive Performance and Metabolic Regulation in Overweight Young Adults With Impaired Glucose Regulation
- ClinicalTrials.gov ID
- NCT07073781
- Acronym / sponsor ID
- ProCog / LBU-Lab4P-ProCogTrial-2025
- 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
- Keywords
- Probiotic supplementation, Psychobiotic, Cognitive performance, Metabolic function, Impaired glucose tolerance, Gut-brain axis
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Leeds Beckett UniversityUniversity, hospital or other
- Collaborators
- Cultech Ltd
- Study start
- 15 Aug 2025 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 20 Aug 2027 (estimated)
- First posted
- 18 Jul 2025 (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.
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 40 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. Increasing evidence suggests that even slightly impaired glucose metabolism (IGM) may contribute to cognitive decline.
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. 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.
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. Functional uncoupling between CBF and regional cerebral glucose metabolism has been directly observed in young adults with IR.
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. 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants will be randomly assigned to one of two parallel groups (Lab4P or placebo) and will receive their assigned intervention daily for 12 weeks. There will be no crossover between groups, and outcomes will be assessed at multiple time points across the intervention period.
| Arm | Type | Receives |
|---|---|---|
| Group receiving the Lab4P probiotic capsules | Experimental | Dietary Supplement: Lab4p Probiotic ConsortiumExperimental group will consume oral dose of 50 billion Colony forming Units (CFU) once daily till delivery. |
| Group receiving the identical, non-active placebo | Placebo comparator | Other: PlaceboMicrocrystalline cellulose/d each, up till delivery |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Aged 18-40 years
- Body Mass Index (BMI) between 25.0 and 29.9 kg/m² (classified as overweight)
- In good general health (self-reported)
- Normal self-reported sleep patterns, with no history of diagnosed sleep disorders
- Willing and able to provide informed consent
Key exclusion criteria (8 listed)
- 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.
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 |
|---|---|---|
| Lab4p Probiotic ConsortiumThe investigational product in this study is Lab4P, a patented multi-strain probiotic consortium formulated as a food supplement and supplied in capsule form. Each daily dose contains a total of 5 × 10¹⁰ CFU of live bacteria, comprising five strains: Lactobacillus acidophilus CUL60 and CUL21, Lactobacillus plantarum CUL66, Bifidobacterium bifidum CUL20, and Bifidobacterium animalis subsp. lactis CUL34. In addition to probiotics, each capsule also contains three micronutrients at 100-200% of the recommended daily intake: Vitamin D (10 µg; 200%), Vitamin C (80 mg; 100%), and Zinc (10 mg; 100%). Lab4P is a marketed, human-approved product manufactured by Cultech Ltd. (Port Talbot, UK) and is classified as a food supplement, available for purchase without prescription. Both the active product and placebo will be identically packaged to maintain blinding. | Dietary supplement | Group receiving the Lab4P probiotic capsules |
| PlaceboPlacebo capsules are composed of microcrystalline cellulose, and are identical in appearance to the test product. | Other | Group receiving the identical, non-active placebo |
Primary outcome
Verbal Memory Performance
Time frame: 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.
37 secondary outcomes
Visual Episodic Memory
Time frame: Baseline to Week 12 (end of treatment).
Number of Participants Reporting One or More Adverse Events (AEs) or Serious Adverse Events (SAEs)
Time frame: Baseline to Week 12 (end of treatment).
Visuospatial Working Memory
Time frame: Baseline to Week 12 (end of treatment).
Executive function (Response Inhibition and Impulse Control)
Time frame: Baseline to Week 12 (end of treatment).
Executive function (Cognitive Flexibility and Attentional Set-Shifting)
Time frame: Baseline to Week 12 (end of treatment).
Processing speed, Psychomotor Response, and Attention
Time frame: Baseline to Week 12 (end of treatment).
Cerebrovascular Reactivity (CVR)
Time frame: Baseline to Week 12 (end of treatment).
Flow-Mediated Dilation (FMD)
Time frame: Baseline to Week 12 (end of treatment).
Global Sleep Quality
Time frame: Baseline to Week 12 (end of treatment).
Sleep Latency
Time frame: Baseline to Week 12 (end of treatment).
Sleep Duration
Time frame: Baseline to Week 12 (end of treatment).
Sleep Efficiency
Time frame: Baseline to Week 12 (end of treatment).
Sleep Disturbances
Time frame: Baseline to Week 12 (end of treatment).
Sleep Medication Use
Time frame: Baseline to Week 12 (end of treatment).
Daytime dysfunction
Time frame: Baseline to Week 12 (end of treatment).
Glycated Haemoglobin (HbA1C)
Time frame: Baseline to Week 12 (end of treatment).
Fasting Blood Glucose
Time frame: Baseline to Week 12 (end of treatment).
Glucose Tolerance (AUC)
Time frame: Baseline to Week 12 (end of treatment).
Systolic blood pressure
Time frame: Baseline to Week 12 (end of treatment).
Diastolic blood pressure
Time frame: Baseline to Week 12 (end of treatment).
Total Cholesterol
Time frame: Baseline to Week 12 (end of treatment).
Low-Density Lipoprotein Cholesterol (LDL-C)
Time frame: Baseline to Week 12 (end of treatment).
High-Density Lipoprotein Cholesterol (HDL-C)
Time frame: Baseline to Week 12 (end of treatment).
Triglycerides
Time frame: Baseline to Week 12 (end of treatment).
Body Mass Index (BMI)
Time frame: Baseline to Week 12 (end of treatment).
Waist-to-Hip Ratio
Time frame: Baseline to Week 12 (end of treatment).
Total Lean Mass
Time frame: Baseline to Week 12 (end of treatment).
Total Fat Mass
Time frame: Baseline to Week 12 (end of treatment).
Percent Body Fat
Time frame: Baseline to Week 12 (end of treatment).
Interleukin-6 (IL-6)
Time frame: Baseline to Week 12 (end of treatment).
Tumor Necrosis Factor-Alpha (TNF-α)
Time frame: Baseline to Week 12 (end of treatment).
Gut Microbiota Diversity
Time frame: Baseline to Week 12 (end of treatment).
Gut Microbiota Community Dispersion
Time frame: Baseline to Week 12 (end of treatment).
Relative Abundance of Microbial Taxa
Time frame: Baseline to Week 12 (end of treatment).
Adherence Rate
Time frame: Baseline to Week 12 (end of treatment).
Physical Discomfort Symptoms
Time frame: Baseline to Week 12 (end of treatment).
Circulating Markers of Platelet Activity
Time frame: Baseline, Week 6, and Week 12.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2026.
- Background: PubMed 27491830Zilliox LA, Chadrasekaran K, Kwan JY, Russell JW. Diabetes and Cognitive Impairment. Curr Diab Rep. 2016 Sep;16(9):87. doi: 10.1007/s11892-016-0775-x.
- Background: PubMed 36902113Webberley TS, Bevan RJ, Kerry-Smith J, Dally J, Michael DR, Thomas S, Rees M, Morgan JE, Marchesi JR, Good MA, Plummer SF, Wang D, Hughes TR. Assessment of Lab4P Probiotic Effects on Cognition in 3xTg-AD Alzheimer's Disease Model Mice and the SH-SY5Y Neuronal Cell Line. Int J Mol Sci. 2023 Feb 28;24(5):4683. doi: 10.3390/ijms24054683.
- Background: PubMed 31030631Sadler JR, Shearrer GE, Burger KS. Alterations in ventral attention network connectivity in individuals with prediabetes. Nutr Neurosci. 2021 Feb;24(2):140-147. doi: 10.1080/1028415X.2019.1609646. Epub 2019 Apr 28.
- Background: PubMed 37703295Ribeiro M, Yordanova YN, Noblet V, Herbet G, Ricard D. White matter tracts and executive functions: a review of causal and correlation evidence. Brain. 2024 Feb 1;147(2):352-371. doi: 10.1093/brain/awad308.
- Background: PubMed 31467393Repple J, Karliczek G, Meinert S, Forster K, Grotegerd D, Goltermann J, Redlich R, Arolt V, Baune BT, Dannlowski U, Opel N. Variation of HbA1c affects cognition and white matter microstructure in healthy, young adults. Mol Psychiatry. 2021 Apr;26(4):1399-1408. doi: 10.1038/s41380-019-0504-3. Epub 2019 Aug 29.
- Background: PubMed 24495302Nazaribadie M, Amini M, Ahmadpanah M, Asgari K, Jamlipaghale S, Nazaribadie S. Executive functions and information processing in patients with type 2 diabetes in comparison to pre-diabetic patients. J Diabetes Metab Disord. 2014 Feb 4;13(1):27. doi: 10.1186/2251-6581-13-27.
- Background: PubMed 33408364Michael DR, Davies TS, Jack AA, Masetti G, Marchesi JR, Wang D, Mullish BH, Plummer SF. Daily supplementation with the Lab4P probiotic consortium induces significant weight loss in overweight adults. Sci Rep. 2021 Jan 6;11(1):5. doi: 10.1038/s41598-020-78285-3.
- Background: PubMed 19026680Lamport DJ, Lawton CL, Mansfield MW, Dye L. Impairments in glucose tolerance can have a negative impact on cognitive function: a systematic research review. Neurosci Biobehav Rev. 2009 Mar;33(3):394-413. doi: 10.1016/j.neubiorev.2008.10.008. Epub 2008 Nov 5.
- Background: PubMed 27489306Kullmann S, Heni M, Hallschmid M, Fritsche A, Preissl H, Haring HU. Brain Insulin Resistance at the Crossroads of Metabolic and Cognitive Disorders in Humans. Physiol Rev. 2016 Oct;96(4):1169-209. doi: 10.1152/physrev.00032.2015. Epub 2016 Aug 3.
- Background: PubMed 35104494Kirvalidze M, Hodkinson A, Storman D, Fairchild TJ, Bala MM, Beridze G, Zuriaga A, Brudasca NI, Brini S. The role of glucose in cognition, risk of dementia, and related biomarkers in individuals without type 2 diabetes mellitus or the metabolic syndrome: A systematic review of observational studies. Neurosci Biobehav Rev. 2022 Apr;135:104551. doi: 10.1016/j.neubiorev.2022.104551. Epub 2022 Jan 29.
- Background: PubMed 38576869Feng L, Gao L. The role of neurovascular coupling dysfunction in cognitive decline of diabetes patients. Front Neurosci. 2024 Mar 21;18:1375908. doi: 10.3389/fnins.2024.1375908. eCollection 2024.
- Background: PubMed 31426413Di Pino A, Urbano F, Scicali R, Di Mauro S, Filippello A, Scamporrino A, Piro S, Purrello F, Rabuazzo AM. 1 h Postload Glycemia Is Associated with Low Endogenous Secretory Receptor for Advanced Glycation End Product Levels and Early Markers of Cardiovascular Disease. Cells. 2019 Aug 16;8(8):910. doi: 10.3390/cells8080910.
- Individual participant dataSharing planned: Yes. De-identified IPD collected during the trial will be shared. This includes outcome-level data related to cognitive performance, sleep quality, glucose regulation, lipid profiles, vascular function, inflammatory biomarkers, body composition, and gut microbiota composition.
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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.
Lewis F Hepburn, Msc principal investigator
Leeds Beckett University
Lauren Owen, PhD study chair
Leeds Beckett University
Steve Trangmar, PhD study chair
Leeds Beckett University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lab4p Probiotic Consortium in people with Impaired Glucose Regulation and Impaired Glucose Tolerance (Prediabetes), run by Leeds Beckett University 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 6 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: looking for participants now, as of the sponsor's last update on 17 Sep 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lewis F Hepburn (+447541333140, l.hepburn3449@student.leedsbeckett.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Verbal Memory Performance (time frame: Baseline to Week 12 (end of treatment).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07073781, which also lists 14 linked publications.
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 17 Sep 2026.