Effect of Mediterranean Diet and Probiotics in Adults With Mild Cognitive Impairment

Sponsor

Pablo Pérez Martínez (Other)

Overall Status

Completed

CT.gov ID

NCT05029765

Collaborator

(none)

Enrollment

Location

Arms

37.3

Actual Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Manipulation of the gut microbiota through dietary modification affects brain function, with improvement in patients with cognitive disorders. Combined effect of nutritional intervention with Mediterranean diet and probiotics with potentially healthy growth of germ, affect the evolution of mild cognitive impairment, by the modulation of components related with the axis microbiota-gut-brain: neuropeptides, short-chain fatty acids, markers for oxidative stress and inflammation.

Condition or Disease	Intervention/Treatment	Phase
Mild Cognitive Impairment	Dietary Supplement: Mediterranean diet Dietary Supplement: Healthy diet (WHO recommendations) Dietary Supplement: Placebo Dietary Supplement: Biopolis-MIX42	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

50 men and women with mild cognitive impairment and more than 60 years will follow three dietary intervention periods of 24 weeks each, with a randomized crossover design. Dietary periods will be: 1.- Healthy diet (WHO recommendations) + placebo; 2.- Mediterranean diet + placebo and ; 3.- Mediterranean diet "plus" (Mediterranean diet + Biopolis-MIX42 (a capsule containing 10^9 colony forming units of Lactobacillus rhamnosus and Bifidobacterium longum)).50 men and women with mild cognitive impairment and more than 60 years will follow three dietary intervention periods of 24 weeks each, with a randomized crossover design. Dietary periods will be: 1.- Healthy diet (WHO recommendations) + placebo; 2.- Mediterranean diet + placebo and ; 3.- Mediterranean diet "plus" (Mediterranean diet + Biopolis-MIX42 (a capsule containing 10^9 colony forming units of Lactobacillus rhamnosus and Bifidobacterium longum)).

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A 24 Weeks Double-blind Latin-square Trial of Effect of Mediterranean Diet and Probiotics in Adults With Mild Cognitive Impairment

Actual Study Start Date :

Jan 26, 2017

Actual Primary Completion Date :

Mar 5, 2020

Actual Study Completion Date :

Mar 5, 2020

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Healthy diet Arm Healthy diet (WHO recommendations) + placebo	Dietary Supplement: Healthy diet (WHO recommendations) Recommendations according to WHO Dietary Supplement: Placebo Placebo
Placebo Comparator: Mediterranean diet Arm Mediterranean diet + placebo	Dietary Supplement: Mediterranean diet Mediterranean diet: 22% Monounsaturated fat, 6% Polyunsaturated fat, 7% Saturated fat, 15% Protein, 50% Carbohydrates Dietary Supplement: Placebo Placebo
Active Comparator: Mediterranean diet "plus" Arm Mediterranean diet + Biopolis-MIX42 (1 capsule per day containing 10^9 colony forming units of Lactobacillus rhamnosus and Bifidobacterium long).	Dietary Supplement: Mediterranean diet Mediterranean diet: 22% Monounsaturated fat, 6% Polyunsaturated fat, 7% Saturated fat, 15% Protein, 50% Carbohydrates Dietary Supplement: Biopolis-MIX42 Biopolis-MIX42: a capsule containing 10^9 colony forming units of Lactobacillus rhamnosus and Bifidobacterium longum.

Arm

Intervention/Treatment

Placebo Comparator: Healthy diet Arm

Healthy diet (WHO recommendations) + placebo

Dietary Supplement: Healthy diet (WHO recommendations)

Recommendations according to WHO

Dietary Supplement: Placebo

Placebo

Placebo Comparator: Mediterranean diet Arm

Mediterranean diet + placebo

Dietary Supplement: Mediterranean diet

Mediterranean diet: 22% Monounsaturated fat, 6% Polyunsaturated fat, 7% Saturated fat, 15% Protein, 50% Carbohydrates

Dietary Supplement: Placebo

Placebo

Active Comparator: Mediterranean diet "plus" Arm

Mediterranean diet + Biopolis-MIX42 (1 capsule per day containing 10^9 colony forming units of Lactobacillus rhamnosus and Bifidobacterium long).

Dietary Supplement: Mediterranean diet

Mediterranean diet: 22% Monounsaturated fat, 6% Polyunsaturated fat, 7% Saturated fat, 15% Protein, 50% Carbohydrates

Dietary Supplement: Biopolis-MIX42

Biopolis-MIX42: a capsule containing 10^9 colony forming units of Lactobacillus rhamnosus and Bifidobacterium longum.

Outcome Measures

Primary Outcome Measures

Cognitive change [Baseline and 24 weeks after each dietary intervention]
Cognitive change in Alzheimer's Disease Assessment Scale-Cognitive-Plus ("ADAS-Cog- Plus"). The total ADAS-Cog-plus score ranges from 0-70 with higher scores suggesting greater impairment.

Secondary Outcome Measures

Microbiota pattern [Baseline and 24 weeks after each dietary intervention]
Changes in the percentage of different families of Microbiota will be analysed during the study
Endotoxemia levels [Baseline and 24 weeks after each dietary intervention]
Changes in the endotoxemia levels will be analysed during the study
Change in inflammatory marker [Baseline and 24 weeks after each dietary intervention]
At time 0 and after 24 weeks of each intervention period and follow-up, the levels of high sesitivity C-reactive protein (hs-CRP) were determined in plasma in mg/dL.
Change in oxidative stress parameters [Baseline and 24 weeks after each dietary intervention]
At time 0 and after 24 weeks of each intervention period and follow-up, the levels of advanced glycation end products (AGEs) were determined in serum in ug/mL: methylglioxal (MG) and N-carboxymethyllysine (CML). Likewise, carbonilated proteins in nmol/mg and lipid peroxidation levels in plasma in ug/mL.
Neurofunctional change [Baseline and 24 weeks after each dietary intervention]
At time 0 and after 24 weeks of each intervention period and follow-up, neurofunctional changes were measured by emission tomography with 2-deoxy-2-[fluorine-18]fluoro- D-glucose (18F-FDG-PET)
Modulation of Microbiota-gut-nervous system [Baseline and 24 weeks after each dietary intervention]
Changes in the plasma levels of molecules with activity on the nervous system were analysed during the study. At time 0 and after 24 weeks of each intervention period and follow-up, Gamma-Aminobutiric acid (GABA) in ng/mL and short-chain fatty acids (acetate, propionate and butirate) in ng/mL were determined in plasma.
Change in cytokine levels [Baseline and 24 weeks after each dietary intervention]
At time 0 and after 24 weeks of each intervention period and follow-up, the levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-a) were determined in plasma in pg/mL.
Neuropeptides modulation [Baseline and 24 weeks after each dietary intervention]
Changes in the plasma levels of molecules with activity on the nervous system were analysed during the study. At time 0 and after 24 weeks of each intervention period and follow-up, Substance P (SP), Y Peptide (PYY), beta-amyloid in pg/mL were determined in plasma.

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age> = 60 years with mild cognitive impairment (Clinical Dementia Rating (CRD) 0.5; Mini Mental Examiantion de Folstein (MMSE)> 23; Repeatable Battery for the Asessment of Neuropsychological Status (RBANS) <= 85)
Drugs with a stable dose from a minimum of 4 weeks prior to screening (excluding psychopharmaceuticals and any other that could affect alertness and cognitive ability)
Geriatric depression scale score <6
Sufficient visual and auditory abilities to carry out the neuropsychological tests. Good health without diseases that prevent the completion of the study.
A minimum educational training established for 6 years or similar work history.
A familiar informant or close caregiver with a minimum contact with the patient established in 10 hours per week that can accompany the participant to the clinical visits

Exclusion Criteria:

Any uncontrolled medical or neurological condition that, in the opinion of the researcher, could contribute to the subject's cognitive impairment (for example, substances abuse, vitamin B12 deficiency, abnormal thyroid function, stroke, or other Cerebral vascular disease, Lewy body dementia, frontotemporal dementia, TBI).
A clinically significant psychiatric illness (eg, major depression, schizophrenia, or bipolar affective disorder) in the 6 months prior to screening.
Transient ischemic attack or cerebrovascular accident or any unexplained loss of consciousness in 1 year before selection (in case of vascular deficit with cognitive sequelae that may still be reversible).
Poorly controlled diabetes mellitus, due to a glycosylated haemoglobin (HbA1c) value of 8% in the selection.
History of unstable angina, myocardial infarction, chronic heart failure (New York Heart Association Class 3 or 4), or clinically significant conduction disorders (unstable atrial fibrillation) within 1 year prior to screening.
Uncontrolled hypertension defined as the mean of 3 measures of systolic blood pressure / diastolic blood pressure> 165/100 mmHg, and persistent systolic blood pressure / diastolic blood pressure > 180/100 mmHg in the 3 months prior to randomization which were considered by the researcher as an indicative of chronic uncontrolled hypertension.
History of seizures in the 10 years prior the selection.
Recent history (within 1 year of screening) of alcohol or substance abuse with positive urine test (looking for non-prescription drugs), alcohol or cannabinoids.
Patients with chronic diseases will be excluded: severe psychiatric, chronic processes in need of treatment such as chronic kidney failure, chronic liver disease, neoplasms under treatment, chronic obstructive pulmonary disease, endocrinopathies susceptible to decompensation and digestive tract diseases.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Reina Sofia University Hospital	Cordoba		Spain

Sponsors and Collaborators

Pablo Pérez Martínez

Investigators

Principal Investigator: Pablo Perez-Martinez, PhD, MD, IMIBIC/ Reina Sofia University Hospital / University of Cordoba

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Pablo Pérez Martínez, Investigator-in-charge at Nutrigenomics Metabolic Syndrome group, Maimónides Biomedical Research Institute of Córdoba

ClinicalTrials.gov Identifier:

NCT05029765

Other Study ID Numbers:

PI16/01777

First Posted:

Sep 1, 2021

Last Update Posted:

Sep 1, 2021

Last Verified:

Aug 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by Pablo Pérez Martínez, Investigator-in-charge at Nutrigenomics Metabolic Syndrome group, Maimónides Biomedical Research Institute of Córdoba

Mild Cognitive Impairment

Probiotics

Microbiota

Mediterranean diet

Additional relevant MeSH terms:

Cognitive Dysfunction

Study Results

No Results Posted as of Sep 1, 2021