An Early Phase 1 interventional study of LpD3.5 and Placebo in Mild Cognitive Impairment (MCI), Cognition and Brain Aging, sponsored by University of South Florida. Recruiting at 1 site in United States. Open to participants aged 60 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-08-31.
Sponsored by University of South Florida · Early Phase 1, Interventional, and Treatment
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.
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.
3,872 studies on the registry are indexed under Cognitive Dysfunction; 1,119 are open to participants now.
This study's planned enrollment of 15 is below the median of 64 across 2,794 interventional studies indexed under Cognitive Dysfunction.
Browse Cognitive Dysfunction studies →University of South Florida is the lead sponsor of 340 studies on the registry; 65 are open to participants now.
Of its 17 completed or terminated interventional studies of FDA-regulated products, 4 (24%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Age 60 years and above; (ii) physician based clinically diagnosed MCI and the (MoCA) score between 18 and 25; iii) LBP ≥ 30 μg/mL in plasma, and (iv) willing to sign , 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:
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.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
MMSE and MoCA
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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
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.
Also known as: Placebo group
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.
Time frame: Baseline to Day 60
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).
Time frame: Baseline to Day 60
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.
Time frame: Baseline to Day 60
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.
Time frame: Baseline to Day 60
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.
Time frame: Baseline to Day 60
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.
Time frame: Baseline to Day 60
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.
Time frame: Baseline to Day 60
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.
Time frame: Baseline to Day 60
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.
Time frame: Baseline to Day 60
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