Back to resultsEffect of Mediterranean Diet and Probiotics in Adults With Mild Cognitive Impairment
Primary Purpose
Mild Cognitive Impairment
Status
Completed
Phase
Not Applicable
Locations
Spain
Study Type
Interventional
Intervention
Mediterranean diet
Healthy diet (WHO recommendations)
Placebo
Biopolis-MIX42
Sponsored by
About this trial
This is an interventional treatment trial for Mild Cognitive Impairment focused on measuring Mild Cognitive Impairment, Probiotics, Microbiota, Mediterranean diet
Eligibility Criteria
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.
Sites / Locations
- Reina Sofia University Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Placebo Comparator
Active Comparator
Arm Label
Healthy diet Arm
Mediterranean diet Arm
Mediterranean diet "plus" Arm
Arm Description
Healthy diet (WHO recommendations) + placebo
Mediterranean diet + placebo
Mediterranean diet + Biopolis-MIX42 (1 capsule per day containing 10^9 colony forming units of Lactobacillus rhamnosus and Bifidobacterium long).
Outcomes
Primary Outcome Measures
Cognitive change
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
Changes in the percentage of different families of Microbiota will be analysed during the study
Endotoxemia levels
Changes in the endotoxemia levels will be analysed during the study
Change in inflammatory marker
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
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
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
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
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05029765
Brief Title
Effect of Mediterranean Diet and Probiotics in Adults With Mild Cognitive Impairment
Official Title
A 24 Weeks Double-blind Latin-square Trial of Effect of Mediterranean Diet and Probiotics in Adults With Mild Cognitive Impairment
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Completed
Study Start Date
January 26, 2017 (Actual)
Primary Completion Date
March 5, 2020 (Actual)
Study Completion Date
March 5, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Pablo Pérez Martínez
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mild Cognitive Impairment
Keywords
Mild Cognitive Impairment, Probiotics, Microbiota, Mediterranean diet
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
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)).
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Healthy diet Arm
Arm Type
Placebo Comparator
Arm Description
Healthy diet (WHO recommendations) + placebo
Arm Title
Mediterranean diet Arm
Arm Type
Placebo Comparator
Arm Description
Mediterranean diet + placebo
Arm Title
Mediterranean diet "plus" Arm
Arm Type
Active Comparator
Arm Description
Mediterranean diet + Biopolis-MIX42 (1 capsule per day containing 10^9 colony forming units of Lactobacillus rhamnosus and Bifidobacterium long).
Intervention Type
Dietary Supplement
Intervention Name(s)
Mediterranean diet
Intervention Description
Mediterranean diet:
22% Monounsaturated fat, 6% Polyunsaturated fat, 7% Saturated fat, 15% Protein, 50% Carbohydrates
Intervention Type
Dietary Supplement
Intervention Name(s)
Healthy diet (WHO recommendations)
Intervention Description
Recommendations according to WHO
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
Placebo
Intervention Type
Dietary Supplement
Intervention Name(s)
Biopolis-MIX42
Intervention Description
Biopolis-MIX42: a capsule containing 10^9 colony forming units of Lactobacillus rhamnosus and Bifidobacterium longum.
Primary Outcome Measure Information:
Title
Cognitive change
Description
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.
Time Frame
Baseline and 24 weeks after each dietary intervention
Secondary Outcome Measure Information:
Title
Microbiota pattern
Description
Changes in the percentage of different families of Microbiota will be analysed during the study
Time Frame
Baseline and 24 weeks after each dietary intervention
Title
Endotoxemia levels
Description
Changes in the endotoxemia levels will be analysed during the study
Time Frame
Baseline and 24 weeks after each dietary intervention
Title
Change in inflammatory marker
Description
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.
Time Frame
Baseline and 24 weeks after each dietary intervention
Title
Change in oxidative stress parameters
Description
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.
Time Frame
Baseline and 24 weeks after each dietary intervention
Title
Neurofunctional change
Description
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)
Time Frame
Baseline and 24 weeks after each dietary intervention
Title
Modulation of Microbiota-gut-nervous system
Description
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.
Time Frame
Baseline and 24 weeks after each dietary intervention
Title
Change in cytokine levels
Description
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.
Time Frame
Baseline and 24 weeks after each dietary intervention
Title
Neuropeptides modulation
Description
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.
Time Frame
Baseline and 24 weeks after each dietary intervention
10. Eligibility
Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pablo Perez-Martinez, PhD, MD
Organizational Affiliation
IMIBIC/ Reina Sofia University Hospital / University of Cordoba
Official's Role
Principal Investigator
Facility Information:
Facility Name
Reina Sofia University Hospital
City
Cordoba
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Effect of Mediterranean Diet and Probiotics in Adults With Mild Cognitive Impairment
We'll reach out to this number within 24 hrs