Brain Aging, Cognition, Gut Inflammation, Inflammaging, Leaky Gut Syndrome, Microbiome Dysbiosis, Mild Cognitive Impairment (MCI)
Conditions
Keywords
Postbiotics, Microbiome, Aging, Longevity, inflammaging, Gut Health, Brain Health, Leaky Gut, Inflammation, Probiotics, Supplement, Dietary, Lifestyle
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.
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.
Interventions
DIETARY_SUPPLEMENTLpD3.5
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.
DIETARY_SUPPLEMENTPlacebo
Inactive ingredients like maltodextrin; placebo capsules contain only inactive ingredients.
Sponsors
University of South Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
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.
Intervention model description
Double blinded cross-over randomized controlled trial.
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Plasma Lipopolysaccharide-Binding Protein (LBP) Level | Baseline to Day 60 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Stool Mucin Level | Baseline to Day 60 | Change in stool mucin level from baseline to Day 60. Stool mucin will be measured using an enzyme-linked immunosorbent assay (ELISA). |
| Change in Plasma C-Reactive Protein (CRP) Level | Baseline to Day 60 | Change in plasma C-reactive protein (CRP) concentration from baseline to Day 60 as a marker of systemic inflammation. |
| Change in Plasma Interleukin-6 (IL-6) Level | Baseline to Day 60 | Change in plasma interleukin-6 (IL-6) concentration from baseline to Day 60 as a marker of systemic inflammation. |
| Change in Plasma Tumor Necrosis Factor-Alpha (TNF-α) Level | Baseline to Day 60 | Change in plasma tumor necrosis factor-alpha (TNF-α) concentration from baseline to Day 60 as a marker of systemic inflammation. |
| Change in Plasma Interleukin-1 Beta (IL-1β) Level | Baseline to Day 60 | Change in plasma interleukin-1 beta (IL-1β) concentration from baseline to Day 60 as a marker of systemic inflammation. |
| Change in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score | Baseline to Day 60 | 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. |
| Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale 14 (ADAS-Cog14) Score | Baseline to Day 60 | 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. |
| Change in Alzheimer's Disease Cooperative Study - Instrumental Activities of Daily Living (ADCS-iADL) Score | Baseline to Day 60 | 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. |
Countries
United States
Contacts
CONTACTHariom Yadav, PhD
CONTACTShalini Jain, PhD
Outcome results
None listed