HIgh Frequency Sampling to sTudy the Physiological Effect of Probiotics on Peripheral Markers of Alzheimer's Pathology: a Proof-of-concept Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- University Hospital, Geneva
- Enrollment
- 3
- Locations
- 1
- Primary Endpoint
- Concentration of plasma AD biomarker, Nfl
Study Overview
Brief Summary
proof-of-concept study to adequately design a larger trial to investigate the effect of supplementation of a probiotic (SLAB51) on AD biomarker.
Detailed Description
BACKGROUND: A growing body of evidence suggests an effect of gut bacteria and their metabolites on brain health, including the development of neurodegenerative conditions and Alzheimer's disease (AD). Probiotic supplementation is commonplace in medicine but targeting the gut microbiome to prevent AD is poorly understood and little is known on the dynamic effects of probiotics on physiology.
AIM: This is a proof-of-concept study to adequately design a larger trial to investigate the effect of supplementation of a probiotic (SLAB51) on AD biomarker. The study will use a high frequency sampling to closely monitor the physiological dynamics as the result of low and high dose consumption of the probiotic.
METHODS: Study subjects will be three patients with prodromal AD between 60 and 80 years old and carrying the apolipoprotein E (APOE) e4 allele. Participants will sequentially receive no supplement (run-in), low and high doses of probiotics for five consecutive days with a washout period in-between. Blood and stools will be collected every day or every second days. The main readout will be the established plasma markers of AD, and more exploratory analysis will be performed on putative mediators of the gut-brain axis.
EXPECTED OUTCOME: Curves of dynamic change of the readouts will be built for each subject, and a model of the response will be estimated. The results of this project will help design a larger trial to identify the most promising analytes showing a dynamic response to probiotic consumption and better understand the link to the pathology.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 60 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Diagnosis of mild cognitive impairment (MCI) due to AD, obtained from the clinical path of the participant in the memory clinic according to the criteria of Petersen et al. 1999 (46)
- •Previous evidence of brain amyloidosis (assessed by positron emission tomographie (PET) or cerebrospinal fluid (CSF))
- •Carrier of APOEe4 gene allele
- •Defecates at least once a day
Exclusion Criteria
- •Antibiotic consumption 1 month prior the intervention
- •Prebiotic consumption 1 month prior the intervention
- •Recent change in diet habit (eg: vegetarian, vegan, high protein diet)
- •Current alcohol addiction
- •Current smoking habit
- •Clinical diagnosis of dementia.
- •Contraindications to probiotic consumption
- •Inability to undergo the procedures of the study, e.g., severe behavioural disturbances.
- •severe diseases:
- •Life threatening diseases,
- •Severe systemic diseases (e.g., kidney insufficiency, cardiac insufficiency, decompensated diabetes, decompensated metabolic diseases, decompensated hypothyroidism, uncontrolled autoimmune diseases);
- •Chronic digestive diseases (e.g.: Crohn's disease, Ulcerative colitis, C. difficile infection)
- •Chronic immune diseases
- •The participation to a clinical trial involving potential Alzheimer's disease modifying therapies.
Arms & Interventions
participant procedure
each participant will go through 3 phases of identical protocol. In each phases blood and stools will be collected at specific days, as well as cardiometabolic measures, transit time, cognitive tests and food consumption.
Each phase last 2 weeks with a washout period of 1 month in between. In the first phase, no treatment will be provided, in the second phase a low dose of probiotic (once a day for five days) will be given and in the third phase high dose of probiotic (twice a day for five days) will be administered.
Intervention: SLAB51 (Dietary Supplement)
Outcomes
Primary Outcomes
Concentration of plasma AD biomarker, Nfl
Time Frame: within a year of last participant finalising the study
The dynamic changes of plasma concentration neurofilament light (NfL in pg/ml), will be reported in the blood shortly before, during and shortly after the consumption of probiotic (low or high doses) as compared to the baseline without treatment.
Concentration of plasma AD biomarker, Amyloid
Time Frame: within a year of last participant finalising the study
The dynamic changes of plasma amyloid concentration, namely Ab40 and Ab42 in pg/ml, will be reported in the blood shortly before, during and shortly after the consumption of probiotic (low or high doses) as compared to the baseline without treatment.
Concentration of plasma AD biomarker, Tau
Time Frame: within a year of last participant finalising the study
The dynamic changes of plasma Tau concentration more specifically p-Tau-181, p-Tau-231 and Tau in pg/ml, will be reported in the blood shortly before, during and shortly after the consumption of probiotic (low or high doses) as compared to the baseline without treatment.
Secondary Outcomes
- Plasma concentration of GFAP(within a year of last participant finalising the study)
- Plasma concentration of VCAM and NCAM(within a year of last participant finalising the study)
- Plasma and stool concentration of bacterial derived metabolites(within a year of last participant finalising the study)
- Plasma concentration of a panel of cytokines(within a year of last participant finalising the study)
- Profiling of gut bacterial population isolated from stools(within a year of last participant finalising the study)
Investigators
Giovanni B. Frisoni
MD Professor
University Hospital, Geneva