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- Ensayo clínico NCT07794956
LpD3.5 Intervention Study in Older Adults- LISA-I Trial (Postbiotics)
A Postbiotics Intervention to Improve Cognitive Function in Older Adults With Mild Cognitive Impairment (Phase 1)
This randomized placebo-controlled clinical study, called the LpD3.5 Intervention Study in Older Adults (LISA), aims to evaluate whether a heat-inactivated postbiotic of human origin (LpD3.5) can serve as a non-pharmacological intervention to reduce gut permeability and inflammation in older adults with mild cognitive impairment (MCI). The study will assess the effects of LpD3.5 supplementation on markers associated with gut health, inflammation, microbiome composition, and cognitive function.
Participants aged 60 years or older with clinically diagnosed MCI will receive either LpD3.5 capsules or placebo capsules for 60 days, followed by a 30-day follow-up period. Biological samples and clinical assessments will be collected to evaluate changes in gut permeability, inflammatory markers, microbiome characteristics, and cognitive outcomes. The findings from this study may provide insight into the potential role of postbiotics as a dietary intervention to improve gut health and related outcomes in older adults with MCI.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
This randomized, placebo-controlled clinical trial, known as the LpD3.5 Intervention Study in Older Adults (LISA), is designed to evaluate whether a heat-inactivated postbiotic of human origin (LpD3.5) can serve as a non-pharmacological intervention to reduce gut permeability and inflammation in older adults with mild cognitive impairment (MCI). The study will assess whether LpD3.5 supplementation can improve gut barrier function, microbiome characteristics, and health-related outcomes associated with cognitive decline.
The primary objective of this study is to determine whether daily oral administration of dietary supplement-grade LpD3.5 (two capsules per day) reduces elevated gut permeability in older adults with MCI, as measured by plasma lipopolysaccharide-binding protein (LBP), a marker associated with intestinal barrier dysfunction.
The secondary objective is to determine whether LpD3.5 supplementation improves gut-related factors, including fecal mucin levels and gut microbiome composition, and whether these changes are associated with reduced inflammation and improved cognitive function. Inflammatory markers in stool and blood, including calprotectin, C-reactive protein (CRP), IL-6, TNF-α, and IL-1β, as well as cognitive outcomes assessed using standardized cognitive measures, will be evaluated.
Exploratory objectives include evaluating changes in blood pTau217 levels and examining potential relationships between LpD3.5 supplementation, gut permeability, microbiome alterations, inflammation, and cognitive function.
The rationale for this study is based on growing evidence that age-related changes in the gut microbiome may contribute to increased intestinal permeability, chronic inflammation, and cognitive decline. Previous preclinical studies have demonstrated that heat-inactivated LpD3.5 improves gut barrier function, reduces inflammation, and enhances cognitive and metabolic outcomes in aging models. This clinical study will investigate whether these beneficial effects translate to older adults with MCI.
Participants aged 60 years or older with clinically diagnosed MCI will be randomized to receive either LpD3.5 capsules or placebo capsules for 60 days, followed by a 30-day follow-up period. The study is designed to provide preliminary evidence regarding the safety, biological effects, and potential mechanisms of LpD3.5 as a dietary postbiotic intervention for improving gut health and related outcomes in older adults with MCI.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase temprana 1
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Hariom Yadav, PhD
- Número de teléfono: 8139748222
- Correo electrónico: hyadav@usf.edu
Copia de seguridad de contactos de estudio
- Nombre: Shalini Jain, PhD
- Número de teléfono: +1 8139746281
- Correo electrónico: jains10@usf.edu
Ubicaciones de estudio
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Florida
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Tampa, Florida, Estados Unidos, 33612
- Reclutamiento
- Department of Neurosurgery and Brain and Spine and Faculty of USF Center for Microbiome Re-search, Microbiomes Institute
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Contacto:
- Hariom Yadav, PhD
- Número de teléfono: 8139748222
- Correo electrónico: hyadav@usf.edu
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Contacto:
- Shalini Jain, PhD
- Correo electrónico: jains10@usf.edu
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
Age 60 years and above; (ii) physician based clinically diagnosed MCI and the Montreal Cognitive Assessment (MoCA) score between 18 and 25; iii) LBP ≥ 30 μg/mL in plasma, and (iv) willing to sign informed consent, take intervention regimen, follow study team guidelines and donate sam-ples, as instructed by the study team; and (iv) live with a partner or care giver
Study partners in this study must meet the following inclusion criteria:
- Be 60 years or older
- Willingness to participate in the study and provide consent
- Ability to have regular contact with the participant(s)
- Be knowledgeable about the participant's health, memory, and daily activities
- Communicate effectively in English
Exclusion Criteria:
Brain and gut related surgery within the past 5 years that affected cognitive function: This information will be collected during the initial telephonic screening through an eligibility checklist. (ii) diagnosis of inflammatory bowel disease, ulcerative colitis, Crohn's disease, acid reflux, gastroesophageal reflux disease, Clostridium difficile infection, or any other gastrointestinal disease that might significantly change the microbiome, gut permeability, and inflammation: Participants will be asked about these diagnoses during the telephonic screening, and responses will be documented : Participants will be asked about these diagnoses during the telephonic screening, and responses will be documented. (iii) history of fecal microbiota transplantation and small intestinal bacterial growth: These conditions will also be screened via the initial eligibility questionnaire ad-ministered during the pre-screening phone interview. (iv) history of cancer or cancer treatment in past 5 years: Participants will be asked to report any history of cancer or treatment during the tele-phonic screening (v) nausea, vomiting, food poisoning, constipation, or diarrhea and/or antibiotic use in the past 30 days; These symptoms will be captured via a brief symptom checklist completed at the time of recruitment as well as on-site at the initial study visit. (vi) heavy consumption of pro-biotics, yogurt, or other fermented food (>4 servings per day): Questionnaire on probiotic yogurt, or other fermented food will be administered during the initial screening by telephonic talk as well as on-site visit to capture this information.(vii) critical or terminal illnesses; (viii) having neurological disorders like epilepsy, Parkinson's disease and Amyotrophic lateral sclerosis: These conditions will be assessed via direct questioning during the telephonic pre-screening interview (ix) pregnant or prisoner: Pregnancy status will be determined via verbal confirmation during screening and documented in the eligibility checklist. (x) unable to eat the test product according to the regulations; (xi) participating in other clinical trial; (xii) any diagnosis or condition that renders the subject ineligible at the discretion of the PI and/or the study team.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Triple
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Comparador activo: LpD3.5 group
This group will receive LpD3.5 (2 capsules per day) for a duration of 60 days with follow-up at 90-day.
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LpD3.5 is a human-origin Lactobacillus paracasei strain, a commonly used probiotic species recognized as safe (GRAS).
The heat-inactivated postbiotic is produced and packaged in certified facilities for human consumption.
Inactive ingredients like maltodextrin; placebo capsules contain only inactive ingredients.
Otros nombres:
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Comparador de placebos: Placebo group
They will receive a bottle of placebo capsules (2 capsules per day) for a duration of 60 days with follow-up at 90 days
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LpD3.5 is a human-origin Lactobacillus paracasei strain, a commonly used probiotic species recognized as safe (GRAS).
The heat-inactivated postbiotic is produced and packaged in certified facilities for human consumption.
Inactive ingredients like maltodextrin; placebo capsules contain only inactive ingredients.
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Change in Plasma Lipopolysaccharide-Binding Protein (LBP) Level
Periodo de tiempo: Baseline to Day 60
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Change in plasma lipopolysaccharide-binding protein (LBP) concentration from baseline to Day 60.
LBP will be measured using an enzyme-linked immunosorbent assay (ELISA) as a marker of elevated gut permeability.
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Baseline to Day 60
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Change in Stool Mucin Level
Periodo de tiempo: Baseline to Day 60
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Change in stool mucin level from baseline to Day 60.
Stool mucin will be measured using an enzyme-linked immunosorbent assay (ELISA).
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Baseline to Day 60
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Change in Plasma C-Reactive Protein (CRP) Level
Periodo de tiempo: Baseline to Day 60
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Change in plasma C-reactive protein (CRP) concentration from baseline to Day 60 as a marker of systemic inflammation.
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Baseline to Day 60
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Change in Plasma Interleukin-6 (IL-6) Level
Periodo de tiempo: Baseline to Day 60
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Change in plasma interleukin-6 (IL-6) concentration from baseline to Day 60 as a marker of systemic inflammation.
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Baseline to Day 60
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Change in Plasma Tumor Necrosis Factor-Alpha (TNF-α) Level
Periodo de tiempo: Baseline to Day 60
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Change in plasma tumor necrosis factor-alpha (TNF-α) concentration from baseline to Day 60 as a marker of systemic inflammation.
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Baseline to Day 60
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Change in Plasma Interleukin-1 Beta (IL-1β) Level
Periodo de tiempo: Baseline to Day 60
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Change in plasma interleukin-1 beta (IL-1β) concentration from baseline to Day 60 as a marker of systemic inflammation.
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Baseline to Day 60
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Change in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score
Periodo de tiempo: Baseline to Day 60
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Change from baseline in the Clinical Dementia Rating - Sum of Boxes (CDR-SB) score.
The CDR-SB evaluates six domains of cognitive and functional performance: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care.
The total score ranges from 0 to 18, with higher scores indicating greater cognitive and functional impairment; therefore, a lower score represents a better outcome.
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Baseline to Day 60
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Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale 14 (ADAS-Cog14) Score
Periodo de tiempo: Baseline to Day 60
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Change from baseline in the Alzheimer's Disease Assessment Scale - Cognitive Subscale 14 (ADAS-Cog14) score.
The ADAS-Cog14 assesses cognitive domains including memory, attention, language, and executive function.
The total score ranges from 0 to 90, with higher scores indicating greater cognitive impairment; therefore, a lower score represents a better outcome.
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Baseline to Day 60
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Change in Alzheimer's Disease Cooperative Study - Instrumental Activities of Daily Living (ADCS-iADL) Score
Periodo de tiempo: Baseline to Day 60
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Change from baseline in the Alzheimer's Disease Cooperative Study - Instrumental Activities of Daily Living (ADCS-iADL) score.
The ADCS-iADL assesses instrumental activities required for independent daily functioning.
The score ranges from 0 to 56, with higher scores indicating better functional ability; therefore, a higher score represents a better outcome.
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Baseline to Day 60
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Colaboradores e Investigadores
Patrocinador
Publicaciones y enlaces útiles
Publicaciones Generales
- Petersen RC, Lopez O, Armstrong MJ, Getchius TSD, Ganguli M, Gloss D, Gronseth GS, Marson D, Pringsheim T, Day GS, Sager M, Stevens J, Rae-Grant A. Practice guideline update summary: Mild cognitive impairment [RETIRED]: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018 Jan 16;90(3):126-135. doi: 10.1212/WNL.0000000000004826. Epub 2017 Dec 27.
- Vemuri R, Gundamaraju R, Shastri MD, Shukla SD, Kalpurath K, Ball M, Tristram S, Shankar EM, Ahuja K, Eri R. Gut Microbial Changes, Interactions, and Their Implications on Human Lifecycle: An Ageing Perspective. Biomed Res Int. 2018 Feb 26;2018:4178607. doi: 10.1155/2018/4178607. eCollection 2018.
- Ma J, Piao X, Mahfuz S, Long S, Wang J. The interaction among gut microbes, the intestinal barrier and short chain fatty acids. Anim Nutr. 2021 Nov 11;9:159-174. doi: 10.1016/j.aninu.2021.09.012. eCollection 2022 Jun.
- Man AL, Bertelli E, Rentini S, Regoli M, Briars G, Marini M, Watson AJ, Nicoletti C. Age-associated modifications of intestinal permeability and innate immunity in human small intestine. Clin Sci (Lond). 2015 Oct;129(7):515-27. doi: 10.1042/CS20150046. Epub 2015 May 7.
- Buford TW. (Dis)Trust your gut: the gut microbiome in age-related inflammation, health, and disease. Microbiome. 2017 Jul 14;5(1):80. doi: 10.1186/s40168-017-0296-0.
- Kim N, Jeon SH, Ju IG, Gee MS, Do J, Oh MS, Lee JK. Transplantation of gut microbiota derived from Alzheimer's disease mouse model impairs memory function and neurogenesis in C57BL/6 mice. Brain Behav Immun. 2021 Nov;98:357-365. doi: 10.1016/j.bbi.2021.09.002. Epub 2021 Sep 6.
- Jemimah S, Chabib CMM, Hadjileontiadis L, AlShehhi A. Gut microbiome dysbiosis in Alzheimer's disease and mild cognitive impairment: A systematic review and meta-analysis. PLoS One. 2023 May 24;18(5):e0285346. doi: 10.1371/journal.pone.0285346. eCollection 2023.
- Alsegiani AS, Shah ZA. The influence of gut microbiota alteration on age-related neuroinflammation and cognitive decline. Neural Regen Res. 2022 Nov;17(11):2407-2412. doi: 10.4103/1673-5374.335837.
- Konig J, Wells J, Cani PD, Garcia-Rodenas CL, MacDonald T, Mercenier A, Whyte J, Troost F, Brummer RJ. Human Intestinal Barrier Function in Health and Disease. Clin Transl Gastroenterol. 2016 Oct 20;7(10):e196. doi: 10.1038/ctg.2016.54.
- Ahmadi S, Wang S, Nagpal R, Wang B, Jain S, Razazan A, Mishra SP, Zhu X, Wang Z, Kavanagh K, Yadav H. A human-origin probiotic cocktail ameliorates aging-related leaky gut and inflammation via modulating the microbiota/taurine/tight junction axis. JCI Insight. 2020 May 7;5(9):e132055. doi: 10.1172/jci.insight.132055.
- Ahmadi S, Razazan A, Nagpal R, Jain S, Wang B, Mishra SP, Wang S, Justice J, Ding J, McClain DA, Kritchevsky SB, Kitzman D, Yadav H. Metformin Reduces Aging-Related Leaky Gut and Improves Cognitive Function by Beneficially Modulating Gut Microbiome/Goblet Cell/Mucin Axis. J Gerontol A Biol Sci Med Sci. 2020 Jun 18;75(7):e9-e21. doi: 10.1093/gerona/glaa056.
- Wang S, Ahmadi S, Nagpal R, Jain S, Mishra SP, Kavanagh K, Zhu X, Wang Z, McClain DA, Kritchevsky SB, Kitzman DW, Yadav H. Lipoteichoic acid from the cell wall of a heat killed Lactobacillus paracasei D3-5 ameliorates aging-related leaky gut, inflammation and improves physical and cognitive functions: from C. elegans to mice. Geroscience. 2020 Feb;42(1):333-352. doi: 10.1007/s11357-019-00137-4. Epub 2019 Dec 8.
- Chaudhari DS, Jain S, Yata VK, Mishra SP, Kumar A, Fraser A, Kociolek J, Dangiolo M, Smith A, Golden A, Masternak MM, Holland P, Agronin M, White-Williams C, Arikawa AY, Labyak CA, Yadav H. Unique trans-kingdom microbiome structural and functional signatures predict cognitive decline in older adults. Geroscience. 2023 Oct;45(5):2819-2834. doi: 10.1007/s11357-023-00799-1. Epub 2023 May 22.
Fechas de registro del estudio
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Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
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Última verificación
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Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- IRB 8263
- USF Microbiome Institute (Otro número de subvención/financiamiento: University of South Florida)
Plan de datos de participantes individuales (IPD)
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Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
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