Effects of Hydroxytyrosol-Rich Olive Polyphenol Dietary Supplement Combined With Mediterranean Diet Adherence on the Cognitive Health of Patients With Mild Cognitive Impairment

NCT07672938 | Recruiting DMC

• 1 other identifier: 107/12-3-2025
• Study Type: interventional
• Target: 141
• Locations: 1 country
• Sites: 1

Brief Summary

Nutrition is an important modifiable risk factor of human cognitive health. Increasing data suggests that certain nutrients or food ingredients, such as plant polyphenols, have the potential to benefit cognitive abilities even in later life. In terms of polyphenols, Hydroxytyrosol (HT) has gained health benefit claims as a potential preventative antioxidant supplementation of neurodegenerative and amyloid-associated diseases while its pharmacological mechanisms suggest protection against cognitive decline. The primary objective of this study will be to evaluate the effects of HT-rich olive juice polyphenol supplementation alongside MeDi adherence compared with placebo alongside MeDi adherence in the prevention of cognitive decline among patients with Mild Cognitive Impairment associated with AD and non-AD pathology.

Conditions

Mild Cognitive Impairment (MCI)

Keywords

Dementia Prevention; Phenolic-rich Nutritional Intervention; Hydroxytyrosol; Mediterranean Diet; Neurodegenerative Biomarkers; Public Health; Clinical Trial

Outcome Measures

Primary Outcomes (1)

• Primary: Mean change on the Alzheimer's Disease (AD) Assessment Scale-Cognitive Subscale (ADAS-Cog) total score from baseline to Week 52 compared with placebo

  The effects of Hydroxytyrosol-Rich Olive Juice Polyphenol Supplement compared with placebo on the cognitive performance of patients with MCI as measured by ADAS-Cog. ADAS-Cog ranges from 0-85 by summing the number of errors made on each task, so that higher scores indicate worse performance.

  From baseline to Week 52

Secondary Outcomes (11)

• Key secondary: Mean change on the Montreal Cognitive Assessment Test (MoCA) total score from baseline to Week 52 compared with placebo

  From baseline to Week 52

• - Mean change on Clinical Dementia Rating - Sum of boxes (CDR-SB) from baseline to Week 52 compared with placebo

  From baseline to Week 52

• Mean change on Mini-Mental State Examination (MMSE) from baseline to Week 52 compared with placebo

  From baseline to Week 52

• - Mean change on Geriatric Depression Scale-15 (GDS-15) from baseline to Week 52 compared with placebo.

  From baseline to Week 52

• - Mean change on Short Anxiety Screening Test (SAST-10) from baseline to Week 52 compared with placebo

  From baseline to Week 52

Other Outcomes (3)

• Mean percentage change in plasma phosphorylated tau 217 (p-tau217) pg/mL from baseline to Week 52 compared with placebo.

  From baseline to Week 52

• Mean percentage change in plasma levels of beta-amyloid 1-42 (Aβ 1-42) pg/mL from baseline to Week 52 compared with placebo.

  From baseline to Week 52

• Mean percentage change in plasma Glial Fibrillary Acidic Protein (GFAP) pg/mL concentration from baseline to Week 52 compared with placebo.

  From baseline to Week 52

Study Arms (3)

Active Arm - Low Dose

ACTIVE COMPARATOR

Low dose: 8 drops (20mg of polyphenols) + Mediterranean Diet instructions

Dietary Supplement: Low-Dose Hydroxytyrosol-Rich Olive Juice Polyphenol Supplement

Experimental Arm - High Dose

EXPERIMENTAL

High dose: 16 drops (40mg of polyphenols) + Mediterranean Diet instructions

Dietary Supplement: High-Dose Hydroxytyrosol-Rich Olive Juice Polyphenol Supplement

Placebo Comparator Arm

PLACEBO COMPARATOR

Placebo 8 drops + Mediterranean Diet instructions

Dietary Supplement: Placebo

Interventions

Low-Dose Hydroxytyrosol-Rich Olive Juice Polyphenol Supplement DIETARY_SUPPLEMENT

This is a prospective, randomised, double-blind, three-arm, placebo-controlled with 1:1:1 randomisation and 52-week follow-up trial. The MEDIPHENO-HTrial study will enrol patients within the Mild Cognitive Impairment spectrum related to AD and non-AD type pathologies. Participants will be randomised to receive either 8 drops of the active HT-high phenolic supplement, or 16 drops of the active HT-high phenolic supplement or 8 drops of the matching placebo. The Mediterranean diet adherence support will be delivered identically to all groups to reduce dietary confounding.

Active Arm - Low Dose

High-Dose Hydroxytyrosol-Rich Olive Juice Polyphenol Supplement DIETARY_SUPPLEMENT

This is a prospective, randomised, double-blind, three-arm, placebo-controlled with 1:1:1 randomisation and 52-week follow-up trial. The MEDIPHENO-HTrial study will enrol patients within the Mild Cognitive Impairment spectrum related to AD and non-AD type pathologies. Participants will be randomised to receive either 8 drops of the active HT-high phenolic supplement, or 16 drops of the active HT-high phenolic supplement or 8 drops of the matching placebo. The Mediterranean diet adherence support will be delivered identically to all groups to reduce dietary confounding.

Experimental Arm - High Dose

Placebo DIETARY_SUPPLEMENT

This is a prospective, randomised, double-blind, three-arm, placebo-controlled with 1:1:1 randomisation and 52-week follow-up trial. The MEDIPHENO-HTrial study will enrol patients within the Mild Cognitive Impairment spectrum related to AD and non-AD type pathologies. Participants will be randomised to receive either 8 drops of the active HT-high phenolic supplement, or 16 drops of the active HT-high phenolic supplement or 8 drops of the matching placebo. The Mediterranean diet adherence support will be delivered identically to all groups to reduce dietary confounding.

Placebo Comparator Arm

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• GR-based men and women aged 50 - 85
• Willingness and ability to conform to the full protocol.
• Ability to accept and sign the consent form.
• Presence of a diagnostic classification of Mild Cognitive Impairment according to the National Institute on Aging and Alzheimer's Association (NIA-AA) framework MCI, which corresponds to stage 3 on the pre-dementia range.
• MoCA score of ≥18 and ≤ 26. Or
• MMSE (Mini-Mental State Examination) score of ≥26 and ≤ 28.
• No active suicide ideation based on the Columbia-Suicide Severity Rating Scale.
• Absence of severe depressive symptomatology based on the Geriatric Depression Scale-15.
• Not using any laxative drugs for at least three days prior to the screening visit.
• Information about APOE status

You may not qualify if:

• Patients with mild, moderate, or severe dementia.
• Current or recent (within the last 4 weeks) engagement with a strict dietary regime i.e., vegetarian / vegan / ketogenic / paleolithic / high protein / weight loss.
• Any known issues with blood taking.
• Any known bleeding disorders.
• Any known allergy to olives, inability to tolerate gluten or multiple allergies/intolerances that would significantly limit food intake.
• Average alcohol use of \>21 glasses per week for men and \>14 glasses per week for women (on average for the last six months).
• History of psychiatric illness including intellectual disability, schizophrenia, bipolar disorder, severe, active depression and alcoholism.
• Neurologic conditions such as vascular dementia, movement disorders, history of conditions such as anaemia and cancer in the last five years, renal or liver failure, malignant tumours, or organ transplant.
• Coffee consumption greater than 5 cups per day.
• Body mass index \> 35 kg/ m2.
• Not taking a stable dose of statins for at least 3 months before the recruitment visit. Taking antibiotics in the 1 week preceding the recruitment visit.
• Pregnancy or lactation.
• Participation in another clinical trial during the last 30 days prior to the recruitment visit.
• Subject taking supplements that may affect lipoprotein metabolism, \>1 g of fish oil/day, antioxidant supplements, cannabidiol (CBD) oil.

Sponsors & Collaborators

• Panhellenic Federation of Alzheimer's Disease and Related Disorders: lead
• Levius Vita Foods srl: collaborator
• Palliative Care Centre "Panagia Glykofilousa", Greek Association of Alzheimer's Disease and Related Disorders, Plastira 65, Thessaloniki 542 50, Greece.: collaborator

Study Sites (1)

Palliative Care Centre "Panagia Glykofilousa", Greek Association of Alzheimer's Disease and Related Disorders, Plastira 65, Thessaloniki 54250, Greece.

Thessaloniki, Central Macedonia, 54250, Greece

RECRUITING

MeSH Terms

Conditions

Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Vilma Chalili

  School of Medicine, Aristotle University of Thessaloniki

  PRINCIPAL INVESTIGATOR

• Magda Tsolaki

  First Department of Neurology, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki

  STUDY CHAIR

Central Study Contacts

Magda Tsolaki, Professor Emeritus, MD, PhD

CONTACT

+30 2310316143; tsolakim1@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2026
• First Posted: June 29, 2026
• Study Start: March 31, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: June 30, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)