Design of Personalised supplemenTs Based on the Gut micRobiota Through Artificial Intelligence for Alzheimer's Patients (TREAT)

Design of Personalised supplemenTs Based on the Gut micRobiota of Alzheimer Patients Through Network and Artificial Intelligence Analysis

Studies indicate that the intestinal microbiota could have an implication in Alzheimer's disease; recently, a positive relationship has been established between levels of bacterial lipopolysaccharide (LPS) and cerebral amyloidosis and a negative relationship between the production of the chain fatty acid cuts butyrate by the intestinal microbiota and cerebral amyloidosis. Currently there is no effective treatment for Alzheimer's, but studies indicate that a healthy diet such as the Mediterranean diet and physical exercise delay the symptoms of this disease. For all these reasons, it is postulated that introducing changes in the intestinal microbiota through diet may be a new treatment or serve as an adjuvant treatment for Alzheimer's disease.

Study Overview

• Status: Not yet recruiting
• Conditions: Alzheimer Disease; Gut Microbiota
• Intervention / Treatment: Dietary supplement: Dietary counseling; Dietary supplement: Personalized diet

Detailed Description

The study consists of three main stages, a first part in which healthy subjects and patients will be characterized. With all the variables obtained, network analyzes and predictive analyzes are carried out in order to see the interaction between variables and determine predictive variables of Alzheimer's disease that could be subject to modification by the diet. In a second stage, the personalized supplement will be designed based on the characteristics of Alzheimer's patients and there is no patient participation. In a third stage, a randomized, parallel nutritional intervention trial will be carried out where the supplement designed "ad hoc" will be compared in the population of Alzheimer's patients against a nutritional supplement commonly used in Alzheimer's patients.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mar Larrosa, PhD; Phone Number: +34913942041; Email: mlarrosa@ucm.es
• Study Contact Backup: Name: Juan Marín Muñoz, MD, PhD; Phone Number: +34968 369 409; Email: juan.marin5@carm.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. to be able to give written consent signed jointly by the patient's legal representative following the rules of the clinical research ethics committee
2. minimum educational level (reading and writing)
3. proficiency of the language of the tests applied; adequate visual and auditory acuity, in the opinion of the researcher, to enable him/her to carry out the tests in the study (compensatory glasses and hearing aids are allowed
4. compliance with the diagnostic criteria of prodromal Alzheimer's Disease according to the criteria of the Institute on Aging- Alzheimer's Association [NIA-AA]: Global Deterioration Scale GDS≥ 2-3
5. Availability of a person ('caregiver') who has frequent and sufficient contact with the subject, so that he/she can provide precise information on the subject's day-to-day life, and attend the visits that are required by the study

Exclusion Criteria:

1. Suffer or have suffered from neurological (epilepsy, sleep disorders, etc.), psychiatric or any other type of pathology (sensory, hepatic, infectious, etc.) which, in the investigator's opinion, may affect their current cognition and functionality
2. Metabolic/endocrine disorders: Type I diabetes, the rest will not be excluded
3. Chronic or sporadic use of antibiotics, antifungals, antivirals or anti-parasitic agents and chronic use of proton pump inhibitors (omeprazole, etc.). The chronic medication that these patients take due to hypertension, diabetes, etc., should be recorded in the database but should not be a criterion for exclusion
4. Suffer from some type of pathology related to the gastrointestinal system or have undergone gastrointestinal surgery (ulcerative colitis, Crohn's disease, bariatric surgery)
5. Pre-menopause or perimenopause

Control patients: recruited among the relatives and companions of the patients and/or in primary care centers in the region of Murcia. The inclusion criteria for the control group will be the same as for the Alzheimer's group except for the requirements regarding cognitive impairment. The intention is for the control group to be similar in age and sex distribution to the Alzheimer's group.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control Human patient (non-Alzheimer) with routine normal diet; Control human patients (30),non suffering from Alzheimer, will continue with their normal dietary habits and samples will be collected.
Sham Comparator: Alzheimer patients with routine normal diet and dietary counseling; Alzheimer patients (30) will continue with their routine normal diet and samples will be collected.	Dietary supplement: Dietary counseling; Dietary advice will be provided to adapt the diet to the nutritional objectives and recommended intakes.
Experimental: Alzheimer patients with personalized diet; Alzheimer patients (30) will be given personalized diet, with supplements based on the gut microbiota (elaborated through AI analyses). Samples will be collected.	Dietary supplement: Personalized diet; Personalized supplement designed by artificial intelligence based on the intestinal microbiota and incorporated into diets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fecal microbiota	Differences in fecal microbiota between healthy controls and Alzheimer's disease participants; Changes in fecal microbiota in Alzheimer's disease participants before and after a nutritional intervention. Microbiota shotgun analysis	Baseline, an average of 1.5 years from baseline and change after three months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dietary habits characterization	Diet characterization of healthy controls and Alzheimer's disease participants - Changes in diet in Alzheimer's disease participants before and after a nutritional intervention 3-day registration questionnaire, a food consumption frequency questionnaire and adherence to mediterranean diet questionnaire will be used. Percentage of macronutrients ingested will be obtained.	Baseline, an average of 1.5 years from baseline and change after three months
Physical activity (PA) characterization	The International Physical Activity Questionnaire for Older People (IPAQ-E) quantifies subjects' activity in minutes per week and categorizes the results into Metabolic Equivalent of Task (MET) values. 1 MET is equivalent to 3.5 mL of oxygen consumed per kg per minute. PA is characterized as: Low: No PA is performed, or the activity is insufficient to reach moderate or high activity. Moderate: Involves three or more days of vigorous PA for at least 25 minutes per day, or five or more days of vigorous PA and/or walking for at least 30 minutes per day. Additionally, achieving an energy expenditure of at least 600 METs per minute per week through a combination of activities. High: Involves vigorous activity at least three days per week, resulting in an energy expenditure of 1500 METs per minute per week. Alternatively, seven or more days of a combination of walking, moderate, and/or vigorous activity, reaching an energy expenditure of at least 3000 METs per minute per week.	Baseline
Blood lipopolysaccharide (LPS)	Changes in LPS in healthy controls and Alzheimer's disease participants - Changes in LPS in Alzheimer's disease participants before and after a nutritional intervention To analyze circulating LPS levels in blood samples	Baseline, an average of 1.5 years from baseline and change after three months
Fecal Short chain fatty acids (SCFA)	Changes in fecal SCFA in healthy controls and Alzheimer's disease participants - Changes in fecal SCFA in Alzheimer's disease participants before and after a nutritional intervention SCFA will be analyzed by High performance liquid chromatography (HPLC)	Baseline, an average of 1.5 years from baseline and change after three months
Metabolomic analysis	Changes in serum and fecal samples in Alzheimer's disease participants before and after a nutritional intervention to search for potential markers of the supplement's effect on health.	An average of 1.5 years from baseline and change after three months
Bile fecal acids	- Changes in fecal bile acids in Alzheimer's disease participants before and after a nutritional intervention Bile fecal acids will be analyzed by High performance liquid chromatography (HPLC)	Baseline, an average of 1.5 years from baseline and change after three months

Collaborators and Investigators

• Sponsor: Universidad Complutense de Madrid
• Collaborators: Universidad Europea de Madrid; Hospital Clínico Universitario Virgen de la Arrixaca
• Investigators: Principal Investigator: Mar Larrosa, PhD, Universidad Complutense de Madrid

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: December 5, 2023
• First Submitted That Met QC Criteria: January 9, 2024
• First Posted (Actual): January 10, 2024

Study Record Updates

• Last Update Posted (Actual): January 10, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Alzheimer's disease; Supplementation; Physical exercise; Artificial intelligence; Gut Microbiota
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: PID2021-123700OB-I00

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No