Dynamic Response to Probiotics in Context of Alzheimer Disease: a Proof-of-concept Study

Not Applicable

Completed

• Conditions: Alzheimer Disease
• Interventions: Dietary Supplement: SLAB51

• Registration Number: NCT05521477
• Lead Sponsor: University Hospital, Geneva

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 Timeline

• Study First Submitted: 2022-08-23
• Study First Submitted QC: 2022-08-25
• Study First Posted: 2022-08-30
• Study Start: 2022-09-01
• Primary Completion: 2024-02-28
• Study Completion: 2024-02-28
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-20
• Last Update Posted: 2025-01-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 3

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
participant procedure	SLAB51	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.

Primary Outcome Measures

Name	Time	Method
Concentration of plasma AD biomarker, Nfl	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	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	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 Outcome Measures

Name	Time	Method
Plasma concentration of GFAP	within a year of last participant finalising the study	The dynamic changes in concentration of plasma glial fibrillary acidic protein (GFAP), as a marker of neuroinflammation, will be reported shortly before, during and shortly after the consumption of probiotic (low or high doses) as compared to the baseline without treatment.
Plasma concentration of VCAM and NCAM	within a year of last participant finalising the study	The dynamic changes in concentration of plasma VCAM and NCAM, as markers of endothelial dysfunction, will be reported shortly before, during and shortly after the consumption of probiotic (low or high doses) as compared to the baseline without treatment.
Plasma and stool concentration of bacterial derived metabolites	within a year of last participant finalising the study	The dynamic changes of plasma and stool concentration of bacterial derived metabolites or small molecules (eg: short chain fatty acids (SCFAs) or lipopolysaccharide (LPS) will be reported shortly before, during and shortly after the consumption of probiotic (low or high doses) as compared to the baseline without treatment.
Plasma concentration of a panel of cytokines	within a year of last participant finalising the study	The dynamic changes in concentraion of a large panel of cytokines measured in plasma, as markers of systemic inflammation, will be reported shortly before, during and shortly after the consumption of probiotic (low or high doses) as compared to the baseline without treatment.
Profiling of gut bacterial population isolated from stools	within a year of last participant finalising the study	The dynamic changes in alpha and beta diversity, as well as the functionality of gut bacterial population isolated from stools will be reported shortly before, during and shortly after the consumption of probiotic (low or high doses) as compared to the baseline without treatment.

Trial Locations

Locations (1)

Geneva University hospitals - Memory clinic; 🇨🇭 Geneva, Switzerland