Clinical trial NCT05521477: Dynamic Response to Probiotics in Context of Alzheimer Disease: a Proof-of-concept Study
Official title: HIgh Frequency Sampling to sTudy the Physiological Effect of Probiotics on Peripheral Markers of Alzheimer's Pathology: a Proof-of-concept Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Alzheimer Disease
Keywords: microbiome
alzheimer disease
probiotic
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
First posted: 2022-08-30
Enrollment: 3
Sex: ALL
Minimum age (years): 60
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The study design will allow to evaluate the dose dependent effect of probiotic consumption on AD blood-based biomarker by comparing each individual to its baseline sampling.

Each participant will follow a 3 phases program of identical procedures:

* Phase I - baseline control: no probiotic will be consumed
* Phase II - Low dose probiotic consumption: 1 dose of probiotic will be taken in the morning for 5 days
* Phase III - High dose probiotic consumption: The subject will receive 1 dose of probiotic in the morning and one dose in the evening for 5 days

In all phases (2 weeks time) blood, stools, cardiometabolic parameter, food frequency, cognitive, anxiety and depression assessment will be collected at specific time points (either shortly before, during or shortly after the treatment period).
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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:

  1. Life threatening diseases,
  2. Severe systemic diseases (e.g., kidney insufficiency, cardiac insufficiency, decompensated diabetes, decompensated metabolic diseases, decompensated hypothyroidism, uncontrolled autoimmune diseases);
  3. Chronic digestive diseases (e.g.: Crohn's disease, Ulcerative colitis, C. difficile infection)
  4. Chronic immune diseases
* The participation to a clinical trial involving potential Alzheimer's disease modifying therapies.

Primary outcomes:
measure: Concentration of plasma AD biomarker, Amyloid
timeFrame: within a year of last participant finalising the study
measure: Concentration of plasma AD biomarker, Tau
timeFrame: within a year of last participant finalising the study
measure: Concentration of plasma AD biomarker, Nfl
timeFrame: within a year of last participant finalising the study
Secondary outcomes:
measure: Plasma concentration of GFAP
timeFrame: within a year of last participant finalising the study
measure: Plasma concentration of a panel of cytokines
timeFrame: within a year of last participant finalising the study
measure: Plasma concentration of VCAM and NCAM
timeFrame: within a year of last participant finalising the study
measure: Profiling of gut bacterial population isolated from stools
timeFrame: within a year of last participant finalising the study
measure: Plasma and stool concentration of bacterial derived metabolites
timeFrame: within a year of last participant finalising the study
Other outcomes:
Locations:
city: Geneva
country: Switzerland
facility: Geneva University hospitals - Memory clinic
Study officials:
affiliation: HUG
name: Giovanni B Frisoni, MD
role: PRINCIPAL_INVESTIGATOR
References: