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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Verbal Memory Performance [Срок оценки: Baseline to Week 12 (end of treatment).]

Вторичные конечные точки (12)

• Visual Episodic Memory [Срок оценки: Baseline to Week 12 (end of treatment).]
• Number of Participants Reporting One or More Adverse Events (AEs) or Serious Adverse Events (SAEs) [Срок оценки: Baseline to Week 12 (end of treatment).]
• Visuospatial Working Memory [Срок оценки: Baseline to Week 12 (end of treatment).]
• Executive function (Response Inhibition and Impulse Control) [Срок оценки: Baseline to Week 12 (end of treatment).]
• Executive function (Cognitive Flexibility and Attentional Set-Shifting) [Срок оценки: Baseline to Week 12 (end of treatment).]
• Processing speed, Psychomotor Response, and Attention [Срок оценки: Baseline to Week 12 (end of treatment).]
• Cerebrovascular Reactivity (CVR) [Срок оценки: Baseline to Week 12 (end of treatment).]
• Flow-Mediated Dilation (FMD) [Срок оценки: Baseline to Week 12 (end of treatment).]
• Global Sleep Quality [Срок оценки: Baseline to Week 12 (end of treatment).]
• Sleep Latency [Срок оценки: Baseline to Week 12 (end of treatment).]
• Sleep Duration [Срок оценки: Baseline to Week 12 (end of treatment).]
• Sleep Efficiency [Срок оценки: Baseline to Week 12 (end of treatment).]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Великобритания · 1 центр

• Leeds Beckett University — Leeds

Публикации

• 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. PMID 27491830
• 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. PMID 36902113
• 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. PMID 31030631
• 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. PMID 37703295
• 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. PMID 31467393
• 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. PMID 24495302
• 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. PMID 33408364
• 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. PMID 19026680

Идентификаторы

NCT: NCT07073781 · LBU-Lab4P-ProCogTrial-2025 · i-NutriLife Hub PoC_R3_012

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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