Management of Mild Cognitive Impairment Patients With Extra Virgin Olive Oil - MICOIL

Study Overview
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Brief Summary
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There is accumulating evidence suggesting that olive oil may have a positive impact on conditions involving cognitive deficits, such as MCI and AD. More specifically, these beneficial effects are mostly attributed to some phenolic compounds in olive oil, such as oleocanthal, oleuropein and ligstroside. Oleocanthal is deeper studied than the rest of olive oil phenol components and it shows promising results in neuroprotection against AD through various suggested mechanisms, such as the enhancement of amyloid-beta clearance in the brain and the inhibition of neurofibrillary tangles formation. For this reason, it would be interesting to study the effects of freshly-pressed extra virgin olive oil, as it is known that it contains oleocanthal in higher concentrations than the normal extra virgin olive oil. The aim of the study is to evaluate the beneficial effect of extra virgin olive oil in comparison to freshly-pressed extra virgin olive oil on patients diagnosed with mild cognitive impairment (MCI). Study Type: Interventional Study Design: Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Prevention

Detailed Description
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OBJECTIVES OF THE TRIAL The objectives of this study are: To investigate the efficacy of freshly pressed EVOO as a disease course modifying treatment for mild cognitive impairment in a phase III double-blind placebo-controlled study. To investigate the effects in objective measurements in patients with mild cognitive impairment. STUDY DESIGN This is a Greek, randomized, double-blind, placebo-controlled study group of EVOO compared with placebo. Qualifying patients will be randomly assigned to receive 50mL of freshly-pressed EVOO or placebo (EVOO) or mediterranean dietary protocol on a daily basis for 24 months. Patients undergo assessments at baseline,12 and 24 months +/- 7 days after beginning treatment. Duration The total study duration will be 30 months. Patients will receive study medication for 24 months. Number of Subjects 150 subjects total will be enrolled. ; 50 in the experimental group (freshly pressed EVOO); 50 in the Control Group 1(EVOO) and 50 in control Group 2(same dietary habits-mediterranean dietary protocol). Patient Eligibility Screening Form (ESF) An eligibility form documenting the patient's fulfillment of the entry criteria will be completed by the assessor. The following information will be included in the ESF: Patient identification: Initials (First initial of first name and First initial of surname), date of birth and Patient Identification Number. Eligibility Screening; Checklist of inclusion and exclusion criteria Eligibility Statement; for patients found to be ineligible, the reason for ineligibility must be stated Written informed consent will be obtained from the subject . The informed consent form must be co-signed by the physician. The nature of the study and the potential risks associated with the trial will be explained to all subject candidates and their responsible informants. Signature and date: the ESF may be completed by an assessor but it is required that the principal investigator/study clinician sign and date the ESF to verify eligibility of the patient for inclusion.

Official Title
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Randomized, Double Blind, Placebo Controlled Prospective Study, to Evaluate the Effect of Freshly-Pressed Extra Virgin Olive Oil in the Disease's Progression in Patients Diagnosed With Mild Cognitive Impairment

Conditions
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Mild Cognitive Impairment

Intervention / Treatment
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* Dietary Supplement: Freshly-Pressed Extra Virgin Olive Oil
* Combination Product: extra virgin olive oil
* Other: mediterranean diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Memory Complaints Abnormal memory function documented by scoring 1 SD below the age-adjusted mean on the Logical Memory II subscale, (Delayed Paragraph Recall) from the Wechsler Memory Scale-R. MMSE 24-30 CDR(sum of boxes) >= 0,5 Diagnosis: Mild Cognitive Impairment (amnestic plus multi-domain) Geriatric Depression Scale (GDS) <6 Hachinski Modified Ischemic scale <= 4 Stability of Permitted Medications for 4 weeks Years of education: >= 5 Proficient language fluency Have a study partner with 10+ hr/wk contact (can be in person and telephone), accompanies to visits Compliance Exclusion Criteria: Visual and auditory acuity inadequate for neuropsychological testing Enrollment in other trials or studies not compatible with MICOIL History of significant neurological or psychiatric illnesses or presence of other diseases precluding enrollment. Use of forbidden medications (listed below) Ferromagnetic implants and devices (including implants or devices held in place by sutures, granulation or ingrowth of tissue, fixation devices, or by other means) not eligible for MRI scanning. Brain malformation or other conditions that may complicate lumbar puncture Medications across the study Excluded Medication: Antidepressants with anti-cholinergic properties. Regular use of narcotic analgesics (>2 doses per week) within 4 weeks of screening. Use of neuroleptics with anti-cholinergic properties (e.g., chlorpromazine, thioridazine) within 4 weeks of screening. Chronic use of other medications with significant central nervous system anticholinergic activity within 4 weeks of screening (e.g., diphenhydramine). Use of Anti-Parkinsonian medications (including Sinemet, amantadine, bromocriptine, pergolide, selegeline) within 4 weeks of screening. Participation in any other investigational drug study within 4 weeks of screening (individuals may not participate in any drug study while participating in this protocol).

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group<br>50 patients Freshly-Pressed Extra Virgin Olive Oil Aluminum bottle with 500 ml of freshly-pressed extra virgin olive oil 1 bottle per 10 days. Dietary Supplement: Freshly-Pressed Extra Virgin Olive Oil dietary intake of the content of 50 mL (3 tablespoons from the bottle containing the product) | Dietary Supplement: Freshly-Pressed Extra Virgin Olive Oil<br>* Dietary Supplement: Freshly-pressed extra virgin olive oil Freshly-Pressed Extra Virgin Olive Oil Aluminum bottle with 500 ml of freshly-pressed extra virgin olive oil 1 bottle per 10 days<br>|
| Placebo Comparator: Control group 1<br>50 patients Extra Virgin Olive Oil Aluminum bottle with 500 ml of freshly-pressed extra virgin olive oil 1 bottle per 10 days. Extra Virgin Olive Oil dietary intake of the content of 50 mL (3 tablespoons from the bottle containing the product) | Combination Product: extra virgin olive oil<br>* Extra Virgin Olive Oil Aluminum bottle with 500 ml of freshly-pressed extra virgin olive oil 1 bottle per 10 days<br>|
| Other: Control Group 2<br>50 patients that will have the same dietary habits and a Mediterranean dietary protocol | Other: mediterranean diet<br>* 50 patients that will have the same dietary habits and a Mediterranean dietary protocol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuropsychological Assessment- Measurements to Assess General Cognitive Function | Changes in Mini-Mental State Examination (MMSE) score | baseline, 12 and 24 months | 
| FUCAS-Measurements to Assess Daily Functionality | Changes in Functional cognitive assessment scale (FUCAS) score | baseline, 12 and 24 months | 
| Letter & Category Fluency Test- Measurement to Assess Verbal Fluency and Learning | Changes in the Letter & Category Fluency Test | baseline, 12 and 24 months | 
| CDR- Measurements to Assess General Cognitive Function | Changes in Global Clinical Dementia Rating (CDR) score (sum of boxes) | baseline, 12 and 24 months | 
| MoCA- Measurements to Assess General Cognitive Function | Changes in Montreal Cognitive Assessment (MoCA) | baseline, 12 and 24 months | 
| CANTAB- Measurements to Assess General Cognitive Function | Changes in Cambridge Neuropsychological Test Automated Battery (CANTAB) | baseline, 12 and 24 months | 
| Clock Drawing test- Measurements to Assess General Cognitive Function | Changes in the Clock Drawing test | baseline, 12 and 24 months | 
| Logical Memory test- Measurements to Assess General Cognitive Function | Changes in the Logical Memory test | baseline, 12 and 24 months | 
| Digit Span Forward & Backward test- Measurements to Assess General Cognitive Function | Changes in the Digit Span Forward & Backward test | baseline, 12 and 24 months | 
| WAIS-R Digit Symbol- Measurements to Assess General Cognitive Function | Changes in the WAIS-R Digit Symbol Substitution Test | baseline, 12 and 24 months | 
| TMT part A and B- Measurements to Assess General Cognitive Function | Changes in the Trail Making Test | baseline, 12 and 24 months | 
| ADASCog-Measurements to Assess Daily Functionality | Changes in Alzheimer's Disease Assessment Scale-Cognitive (ADASCog) | baseline, 12 and 24 months | 
| Functional Rating Scale for Dementia-Measurements to Assess Daily Functionality | Changes in Functional Rating Scale for Dementia (FRSSD) | baseline, 12 and 24 months | 
| Auditory Verbal Learning Test- Measurement to Assess Verbal Fluency and Learning | Changes in the Auditory Verbal Learning Test | baseline, 12 and 24 months | 
| Boston Naming Test- Measurement to Assess Verbal Fluency and Learning | Changes in the Boston Naming Test | baseline, 12 and 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NeuroImaging | Changes in brain Magnetic Resonance Imaging (MRI) 1.5 Tesla (brain atrophy) [Time Frame: baseline, 24 month] | baseline and 24 months | 
| CSF - beta amyloid | Changes in mean values on high sensitivity beta-amyloid 1-42 protein | baseline and 24 months | 
| CSF TAU-protein | Changes in mean values on TAU-protein in cerebrospinal fluid | baseline and 24 months | 
| Neurophysiology and ERPs | •Changes in Event-Related Potential (ERP) (oddball paradigm, auditory ERPs) [Time frame: baseline, 12 month, 24 month] | baseline, 12 and 24 months | 
| Electroencephalography recording | •Changes in Electroencephalography (EEG), resting state.The device records brain signals through 57 electrodes, 2 reference electrodes attached to the earlobes, and a ground electrode placed at a left anterior position. [Time frame: baseline, 12 month, 24 month] | baseline, 12 and 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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extra virgin olive oil, mild cognitive impairment, randomized double blind clinical trial