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Mild Cognitive Impairment (MCI)Early Phase 1PostbioticsNCT07794956

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

A Early Phase 1 study testing LpD3.5 in people with Mild Cognitive Impairment (MCI) and Cognition, run by University of South Florida at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 60 years and olderHealthy volunteers can take part
What is being tested?
LpD3.5
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
15 participants
Where
1 siteUnited States
Study dates
3 Mar 2026to 15 Nov 2026
Phase
Early Phase 1
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 60 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Hariom Yadav, PhD contact

8139748222

hyadav@usf.edu

Shalini Jain, PhD contact

+1 8139746281

jains10@usf.edu

United States1 site, 1 recruiting

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

    Tampa, Florida, 33612

    Hariom Yadav, PhD, 8139748222, hyadav@usf.edu

    Shalini Jain, PhD, jains10@usf.edu

    Recruiting

Other trials in United States

About this study

Official title: 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.

Read the detailed description

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.

Being tested
LpD3.5, Placebo
Keywords
Postbiotics, Microbiome, Aging, Longevity, inflammaging, Gut Health, Brain Health, Leaky Gut, Inflammation, Probiotics, Supplement, Dietary, Lifestyle
Medical subject headings
Cognitive Dysfunction, Inflammation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LpD3.5Dietary 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.

  • PlaceboDietary supplement

    Also called Placebo group

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

Study groups in NCT07794956
Study groupRoleWhat they receive
LpD3.5 groupActive comparatorThis group will receive LpD3.5 (2 capsules per day) for a duration of 60 days with follow-up at 90-day.
Receives: Dietary Supplement: LpD3.5; Dietary Supplement: Placebo
Placebo groupPlacebo comparatorThey will receive a bottle of placebo capsules (2 capsules per day) for a duration of 60 days with follow-up at 90 days
Receives: Dietary Supplement: LpD3.5; Dietary Supplement: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline to Day 60

Secondary outcomes (8)

  1. Change in Stool Mucin Level

    Change in stool mucin level from baseline to Day 60. Stool mucin will be measured using an enzyme-linked immunosorbent assay (ELISA).

    Measured: Baseline to Day 60

  2. Change in Plasma C-Reactive Protein (CRP) Level

    Change in plasma C-reactive protein (CRP) concentration from baseline to Day 60 as a marker of systemic inflammation.

    Measured: Baseline to Day 60

  3. Change in Plasma Interleukin-6 (IL-6) Level

    Change in plasma interleukin-6 (IL-6) concentration from baseline to Day 60 as a marker of systemic inflammation.

    Measured: Baseline to Day 60

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

    Change in plasma tumor necrosis factor-alpha (TNF-α) concentration from baseline to Day 60 as a marker of systemic inflammation.

    Measured: Baseline to Day 60

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

    Change in plasma interleukin-1 beta (IL-1β) concentration from baseline to Day 60 as a marker of systemic inflammation.

    Measured: Baseline to Day 60

  6. Change in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score

    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.

    Measured: Baseline to Day 60

  7. Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale 14 (ADAS-Cog14) Score

    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.

    Measured: Baseline to Day 60

  8. Change in Alzheimer's Disease Cooperative Study - Instrumental Activities of Daily Living (ADCS-iADL) Score

    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.

    Measured: Baseline to Day 60

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2026
  2. Study start3 Mar 2026
  3. Primary completion15 Nov 2026 (estimated)
  4. Study completion15 Nov 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Double blinded cross-over randomized controlled trial.
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
15 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07794956
Sponsor's protocol ID
IRB 8263
Other IDs
USF Microbiome Institute
Acronym
Postbiotics
Status last verified
Aug 2026
First submitted
24 Aug 2026
Last updated
31 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 29682542

  • 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.

    PubMed 35573092

  • 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.

    PubMed 25948052

  • 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.

    PubMed 28709450

  • 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.

    PubMed 34500036

  • 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.

    PubMed 37224131

  • 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.

    PubMed 35535879

  • 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.

    PubMed 27763627

  • 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.

    PubMed 32302292

  • 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.

    PubMed 32129462

  • 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.

    PubMed 31814084

  • 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.

    PubMed 37213047

  • 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.

    PubMed 29282327

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing LpD3.5 in people with Mild Cognitive Impairment (MCI) and Cognition, run by University of South Florida at 1 site in United States.

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 7 inclusion and 1 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 31 Aug 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 States. 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.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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 Hariom Yadav, PhD (8139748222, hyadav@usf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Plasma Lipopolysaccharide-Binding Protein (LBP) Level (time frame: Baseline to Day 60). 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 NCT07794956, which also lists 13 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 31 Aug 2026.

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