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

Alzheimer Disease Clinical Trial

— HISTEPPA  

Official title:

HIgh Frequency Sampling to sTudy the Physiological Effect of Probiotics on Peripheral Markers of Alzheimer's Pathology: a Proof-of-concept Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05521477
• Other study ID #: 2022-01052
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 1, 2022
• Est. completion date: September 1, 2023

Study information

• Verified date: August 2022
• Source: University Hospital, Geneva
• Contact: Giovanni B Frisoni, MD
• Phone: +41 (0)22 372 58 01
• Email: Giovanni.Frisoni[@]unige.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

proof-of-concept study to adequately design a larger trial to investigate the effect of supplementation of a probiotic (SLAB51) on AD biomarker.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 3
• Est. completion date: September 1, 2023
• Est. primary completion date: September 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Dietary Supplement:
• SLAB51
One dose of probiotic consists of a bag of probiotic powder to dissolve in a glass of water according to the manufacturer instructions. Each bag contains 100 billion bacteria of the following strains: streptococcus thermophilus DSM 32245, 2 Bifidobacteria lactis DSM 32246 and DSM 32247, Lactobacillus acidophilus DSM 32241, Lactobacillus helveticus DSM 32242, Lactobacillus paracasei DSM 32243, Lactobacillus plantarum DSM 32244 and Lactobacillus brevis DSM 27961.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Geneva

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concentration of plasma AD biomarker, Amyloid	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.	within a year of last participant finalising the study
Primary	Concentration of plasma AD biomarker, Tau	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.	within a year of last participant finalising the study
Primary	Concentration of plasma AD biomarker, Nfl	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.	within a year of last participant finalising the study
Secondary	Plasma concentration of GFAP	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.	within a year of last participant finalising the study
Secondary	Plasma concentration of a panel of cytokines	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.	within a year of last participant finalising the study
Secondary	Plasma concentration of VCAM and NCAM	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.	within a year of last participant finalising the study
Secondary	Profiling of gut bacterial population isolated from stools	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.	within a year of last participant finalising the study
Secondary	Plasma and stool concentration of bacterial derived metabolites	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.	within a year of last participant finalising the study