Mild Cognitive ImpairmentNCT05029765
Effect of Mediterranean Diet and Probiotics in Adults With Mild Cognitive Impairment
A study testing Mediterranean diet, Healthy diet (WHO recommendations) and Biopolis-MIX42 in people with Mild Cognitive Impairment, run by Pablo Pérez Martínez at 1 site in Spain.
Trial 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… Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Mild Cognitive Impairment
- What is being tested?
- Mediterranean diet, Healthy diet (WHO recommendations) and Biopolis-MIX42
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteSpain
- Study dates
- 26 Jan 2017to 5 Mar 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A 24 Weeks Double-blind Latin-square Trial of Effect of Mediterranean Diet and Probiotics in Adults With Mild Cognitive Impairment
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.
- Conditions
- Mild Cognitive Impairment
- Being tested
- Mediterranean diet, Healthy diet (WHO recommendations), Placebo, Biopolis-MIX42
- Keywords
- Mild Cognitive Impairment, Probiotics, Microbiota, Mediterranean diet
- Medical subject headings
- Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mediterranean dietDietary supplement
Mediterranean diet:
22% Monounsaturated fat, 6% Polyunsaturated fat, 7% Saturated fat, 15% Protein, 50% Carbohydrates
Healthy diet (WHO recommendations)Dietary supplement
Recommendations according to WHO
PlaceboDietary supplement
Placebo
Biopolis-MIX42Dietary supplement
Biopolis-MIX42: a capsule containing 10^9 colony forming units of Lactobacillus rhamnosus and Bifidobacterium longum.
| Study group | Role | What they receive |
|---|---|---|
| Healthy diet Arm | Placebo comparator | Healthy diet (WHO recommendations) + placebo Receives: Dietary Supplement: Healthy diet (WHO recommendations); Dietary Supplement: Placebo |
| Mediterranean diet Arm | Placebo comparator | Mediterranean diet + placebo Receives: Dietary Supplement: Mediterranean diet; Dietary Supplement: Placebo |
| Mediterranean diet "plus" Arm | Active comparator | Mediterranean diet + Biopolis-MIX42 (1 capsule per day containing 10^9 colony forming units of Lactobacillus rhamnosus and Bifidobacterium long). Receives: Dietary Supplement: Mediterranean diet; Dietary Supplement: Biopolis-MIX42 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and 24 weeks after each dietary intervention
Secondary outcomes (8)
Microbiota pattern
Changes in the percentage of different families of Microbiota will be analysed during the study
Measured: Baseline and 24 weeks after each dietary intervention
Endotoxemia levels
Changes in the endotoxemia levels will be analysed during the study
Measured: Baseline and 24 weeks after each dietary intervention
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.
Measured: Baseline and 24 weeks after each dietary intervention
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.
Measured: Baseline and 24 weeks after each dietary intervention
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)
Measured: Baseline and 24 weeks after each dietary intervention
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.
Measured: Baseline and 24 weeks after each dietary intervention
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.
Measured: Baseline and 24 weeks after each dietary intervention
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.
Measured: Baseline and 24 weeks after each dietary intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2021
- Study start26 Jan 2017
- Primary completion5 Mar 2020
- Study completion5 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pablo Pérez Martínez
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Pablo Pérez Martínez, Maimónides Biomedical Research Institute of Córdoba
- Investigators
- Pablo Perez-Martinez, PhD, MD, Principal investigator, IMIBIC/ Reina Sofia University Hospital / University of Cordoba
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05029765
- Sponsor's protocol ID
- PI16/01777
- Status last verified
- Aug 2021
- First submitted
- 14 Jun 2018
- Last updated
- 1 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cruz M, Martinez-Huelamo M, Yubero-Serrano EM, Cubedo-Cullere M, Mora-Ortiz M, Guadall A, Sanchez-Pla A, Wishart DS, Andres-Lacueva C, Perez-Martinez P, Merono T. Enhanced metabolic flexibility links Mediterranean diet with cognition: interim findings from a randomized controlled trial. Food Funct. 2026 Aug 17;17(16):7303-7316. doi: 10.1039/d5fo05544j.
PubMed 42504863Cardelo MP, Corina A, Leon-Acuna A, Quintana-Navarro GM, Alcala-Diaz JF, Rangel-Zuniga OA, Camargo A, Conde-Gavilan C, Carmona-Medialdea C, Vallejo-Casas JA, Carmona-Asenjo E, Ochoa-Sepulveda JJ, Aguera-Morales E, Delgado-Lista J, Katsiki N, Lopez-Miranda J, Perez-Jimenez F, Yubero-Serrano EM, Perez-Martinez P. Effect of the Mediterranean diet and probiotic supplementation in the management of mild cognitive impairment: Rationale, methods, and baseline characteristics. Front Nutr. 2022 Dec 8;9:1037842. doi: 10.3389/fnut.2022.1037842. eCollection 2022.
PubMed 36570150
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 24 Weeks Double-blind Latin-square Trial of Effect of Mediterranean Diet and Probiotics in Adults With Mild Cognitive Impairment
- ClinicalTrials.gov ID
- NCT05029765
- Acronym / sponsor ID
- PI16/01777
- Conditions
- Mild Cognitive Impairment
- Keywords
- Mild Cognitive Impairment, Probiotics, Microbiota, Mediterranean diet
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Pablo Pérez MartínezUniversity, hospital or other
- Study start
- 26 Jan 2017 (actual)
- Primary completion
- 5 Mar 2020 (actual)
- Study completion
- 5 Mar 2020 (actual)
- First posted
- 1 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
- 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)).
| Arm | Type | Receives |
|---|---|---|
| Healthy diet Arm | Placebo comparator | Dietary Supplement: Healthy diet (WHO recommendations), Dietary Supplement: PlaceboHealthy diet (WHO recommendations) + placebo |
| Mediterranean diet Arm | Placebo comparator | Dietary Supplement: Mediterranean diet, Dietary Supplement: PlaceboMediterranean diet + placebo |
| Mediterranean diet "plus" Arm | Active comparator | Dietary Supplement: Mediterranean diet, Dietary Supplement: Biopolis-MIX42Mediterranean diet + Biopolis-MIX42 (1 capsule per day containing 10^9 colony forming units of Lactobacillus rhamnosus and Bifidobacterium long). |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mediterranean dietMediterranean diet: 22% Monounsaturated fat, 6% Polyunsaturated fat, 7% Saturated fat, 15% Protein, 50% Carbohydrates | Dietary supplement | Mediterranean diet "plus" Arm, Mediterranean diet Arm |
| Healthy diet (WHO recommendations)Recommendations according to WHO | Dietary supplement | Healthy diet Arm |
| PlaceboPlacebo | Dietary supplement | Healthy diet Arm, Mediterranean diet Arm |
| Biopolis-MIX42Biopolis-MIX42: a capsule containing 10^9 colony forming units of Lactobacillus rhamnosus and Bifidobacterium longum. | Dietary supplement | Mediterranean diet "plus" Arm |
Primary outcome
Cognitive change
Time frame: 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.
8 secondary outcomes
Microbiota pattern
Time frame: Baseline and 24 weeks after each dietary intervention
Endotoxemia levels
Time frame: Baseline and 24 weeks after each dietary intervention
Change in inflammatory marker
Time frame: Baseline and 24 weeks after each dietary intervention
Change in oxidative stress parameters
Time frame: Baseline and 24 weeks after each dietary intervention
Neurofunctional change
Time frame: Baseline and 24 weeks after each dietary intervention
Modulation of Microbiota-gut-nervous system
Time frame: Baseline and 24 weeks after each dietary intervention
Change in cytokine levels
Time frame: Baseline and 24 weeks after each dietary intervention
Neuropeptides modulation
Time frame: Baseline and 24 weeks after each dietary intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2021.
- Derived from this study: PubMed 42504863Cruz M, Martinez-Huelamo M, Yubero-Serrano EM, Cubedo-Cullere M, Mora-Ortiz M, Guadall A, Sanchez-Pla A, Wishart DS, Andres-Lacueva C, Perez-Martinez P, Merono T. Enhanced metabolic flexibility links Mediterranean diet with cognition: interim findings from a randomized controlled trial. Food Funct. 2026 Aug 17;17(16):7303-7316. doi: 10.1039/d5fo05544j.
- Derived from this study: PubMed 36570150Cardelo MP, Corina A, Leon-Acuna A, Quintana-Navarro GM, Alcala-Diaz JF, Rangel-Zuniga OA, Camargo A, Conde-Gavilan C, Carmona-Medialdea C, Vallejo-Casas JA, Carmona-Asenjo E, Ochoa-Sepulveda JJ, Aguera-Morales E, Delgado-Lista J, Katsiki N, Lopez-Miranda J, Perez-Jimenez F, Yubero-Serrano EM, Perez-Martinez P. Effect of the Mediterranean diet and probiotic supplementation in the management of mild cognitive impairment: Rationale, methods, and baseline characteristics. Front Nutr. 2022 Dec 8;9:1037842. doi: 10.3389/fnut.2022.1037842. eCollection 2022.
- Individual participant dataSharing planned: No
Related trials for Mild Cognitive Impairment
RecruitingPhase 1
PET Imaging of Phosphodiesterase-4 (PDE4) in Volunteers With Alzheimer Disease (AD) or Mild Cognitive Impairment (MCI)
Alzheimer s Disease, Mild Cognitive Impairment
RecruitingObservational study
Community-based Screening for Alzheimer's Disease
Alzheimer's Disease(AD), Mild Cognitive Impairment (MCI)
RecruitingObservational study
InRAD Observational Study
Alzheimer's Disease(AD), Mild Cognitive Impairment (MCI)
Recruiting
Treating Insomnia in Mild Cognitive Impairment
Mild Cognitive Impairment (MCI), Insomnia
Recruiting
Telehealth-Adapted Compensatory Training and Intervention for Cognition
MCI, Mild Cognitive Impairment
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pablo Perez-Martinez, PhD, MD principal investigator
IMIBIC/ Reina Sofia University Hospital / University of Cordoba
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Mediterranean diet, Healthy diet (WHO recommendations) and Biopolis-MIX42 in people with Mild Cognitive Impairment, run by Pablo Pérez Martínez at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cognitive change (time frame: Baseline and 24 weeks after each dietary intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05029765, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2021.