LpD3.5 Intervention Study in Older Adults- LISA-I Trial

NCT07794956 | Recruiting Early Phase 1

• 2 other identifiers: IRB 8263USF Microbiome Institute
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mild Cognitive Impairment (MCI); Cognition; Brain Aging; Microbiome Dysbiosis; Leaky Gut Syndrome; Gut Inflammation; Inflammaging

Keywords

Postbiotics; Microbiome; Aging; Longevity; inflammaging; Gut Health; Brain Health; Leaky Gut; Inflammation; Probiotics; Supplement; Dietary; Lifestyle

Outcome Measures

Primary Outcomes (1)

• Change in Plasma Lipopolysaccharide-Binding Protein (LBP) Level

  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.

  Baseline to Day 60

Secondary Outcomes (8)

• Change in Stool Mucin Level

  Baseline to Day 60

• Change in Plasma C-Reactive Protein (CRP) Level

  Baseline to Day 60

• Change in Plasma Interleukin-6 (IL-6) Level

  Baseline to Day 60

• Change in Plasma Tumor Necrosis Factor-Alpha (TNF-α) Level

  Baseline to Day 60

• Change in Plasma Interleukin-1 Beta (IL-1β) Level

  Baseline to Day 60

Study Arms (2)

LpD3.5 group

ACTIVE COMPARATOR

This group will receive LpD3.5 (2 capsules per day) for a duration of 60 days with follow-up at 90-day.

Dietary Supplement: LpD3.5; Dietary Supplement: Placebo

Placebo group

PLACEBO COMPARATOR

They will receive a bottle of placebo capsules (2 capsules per day) for a duration of 60 days with follow-up at 90 days

Dietary Supplement: LpD3.5; Dietary Supplement: Placebo

Interventions

LpD3.5 DIETARY_SUPPLEMENT

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.

LpD3.5 group; Placebo group

Placebo DIETARY_SUPPLEMENT

Inactive ingredients like maltodextrin; placebo capsules contain only inactive ingredients.

Also known as: Placebo group

LpD3.5 group; Placebo group

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of South Florida: lead

Study Sites (1)

Department of Neurosurgery and Brain and Spine and Faculty of USF Center for Microbiome Re-search, Microbiomes Institute

Tampa, Florida, 33612, United States

RECRUITING

Related Publications (13)

• 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.

  PMID: 29682542 RESULT

• 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.

  PMID: 35573092 RESULT

• 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.

  PMID: 25948052 RESULT

• 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.

  PMID: 28709450 RESULT

• 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.

  PMID: 34500036 RESULT

• 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.

  PMID: 37224131 RESULT

• 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.

  PMID: 35535879 RESULT

• 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.

  PMID: 27763627 RESULT

• 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.

  PMID: 32302292 RESULT

• 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.

  PMID: 32129462 RESULT

• 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.

  PMID: 31814084 RESULT

• 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.

  PMID: 37213047 RESULT

• 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.

  PMID: 29282327 RESULT

MeSH Terms

Conditions

Cognitive Dysfunction; Inflammation

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Hariom Yadav, PhD

CONTACT

8139748222; hyadav@usf.edu

Shalini Jain, PhD

CONTACT

+1 8139746281; jains10@usf.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Participants, study investigators, research staff, and outcome assessors will remain blinded to treatment assignment. The LpD3.5 and placebo products will be matched to maintain blinding throughout the intervention period. Treatment allocation will remain concealed until completion of the primary analysis, unless unblinding is required for safety reasons.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double blinded cross-over randomized controlled trial.

Study Record Dates

• First Submitted: August 24, 2026
• First Posted: August 31, 2026
• Study Start: March 3, 2026
• Primary Completion (Estimated): November 15, 2026
• Study Completion (Estimated): November 15, 2026
• Last Updated: August 31, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)