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

NCT ID: NCT07073781

Last Updated: 2025-12-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-08-15

Study Completion Date

2026-08-20

Brief Summary

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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

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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

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Group receiving the Lab4P probiotic capsules

Experimental group will consume oral dose of 50 billion Colony forming Units (CFU) once daily till delivery.

Group Type EXPERIMENTAL

Lab4p Probiotic Consortium

Intervention Type DIETARY_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.

Group receiving the identical, non-active placebo

Microcrystalline cellulose/d each, up till delivery

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Placebo capsules are composed of microcrystalline cellulose, and are identical in appearance to the test product.

Interventions

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Lab4p Probiotic Consortium

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.

Intervention Type DIETARY_SUPPLEMENT

Placebo

Placebo capsules are composed of microcrystalline cellulose, and are identical in appearance to the test product.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Aged 18-35 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

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cultech Ltd, Port Talbot, UK

UNKNOWN

Sponsor Role collaborator

Leeds Beckett University

OTHER

Sponsor Role lead

Responsible Party

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Lewis Hepburn

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Lewis F Hepburn, Msc

Role: PRINCIPAL_INVESTIGATOR

Leeds Beckett University

Lauren Owen, PhD

Role: STUDY_CHAIR

Leeds Beckett University

Steve Trangmar, PhD

Role: STUDY_CHAIR

Leeds Beckett University

Locations

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Leeds Beckett University

Leeds, Greater Manchester, United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Lewis F Hepburn

Role: CONTACT

+447541333140

Facility Contacts

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Lewis F Hepburn

Role: primary

+447541333140

References

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Feng 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.

Reference Type BACKGROUND
PMID: 38576869 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27491830 (View on PubMed)

Webberley 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.

Reference Type BACKGROUND
PMID: 36902113 (View on PubMed)

Sadler 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.

Reference Type BACKGROUND
PMID: 31030631 (View on PubMed)

Ribeiro 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.

Reference Type BACKGROUND
PMID: 37703295 (View on PubMed)

Repple 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.

Reference Type BACKGROUND
PMID: 31467393 (View on PubMed)

Nazaribadie 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.

Reference Type BACKGROUND
PMID: 24495302 (View on PubMed)

Michael 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.

Reference Type BACKGROUND
PMID: 33408364 (View on PubMed)

Lamport 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.

Reference Type BACKGROUND
PMID: 19026680 (View on PubMed)

Kullmann 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.

Reference Type BACKGROUND
PMID: 27489306 (View on PubMed)

Kirvalidze 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.

Reference Type BACKGROUND
PMID: 35104494 (View on PubMed)

Di 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.

Reference Type BACKGROUND
PMID: 31426413 (View on PubMed)

Deery 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.

Reference Type BACKGROUND
PMID: 38914735 (View on PubMed)

Deery 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.

Reference Type BACKGROUND
PMID: 40604159 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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i-NutriLife Hub PoC_R3_012

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

LBU-Lab4P-ProCogTrial-2025

Identifier Type: -

Identifier Source: org_study_id

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