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

Official title

Hydroxytyrosol-Rich Olive Juice Polyphenol and Mediterranean Diet (The MEDIPHENO-HTrial) in Prevention of Cognitive Decline in Community-Dwelling Patients With Mild Cognitive Impairment: A Double-Blind, Placebo-Controlled, 3-Arm, Randomised Controlled Clinical Study

Overview

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.

Interventions

• Dietary supplement Low-Dose Hydroxytyrosol-Rich Olive Juice Polyphenol 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
• Dietary supplement High-Dose Hydroxytyrosol-Rich Olive Juice Polyphenol 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
• Dietary supplement Placebo
  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

Primary outcome measures

• 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 [Time frame: From baseline to Week 52]

Secondary outcome measures (11)

• Key secondary: Mean change on the Montreal Cognitive Assessment Test (MoCA) total score from baseline to Week 52 compared with placebo [Time frame: From baseline to Week 52]
• - Mean change on Clinical Dementia Rating - Sum of boxes (CDR-SB) from baseline to Week 52 compared with placebo [Time frame: From baseline to Week 52]
• Mean change on Mini-Mental State Examination (MMSE) from baseline to Week 52 compared with placebo [Time frame: From baseline to Week 52]
• - Mean change on Geriatric Depression Scale-15 (GDS-15) from baseline to Week 52 compared with placebo. [Time frame: From baseline to Week 52]
• - Mean change on Short Anxiety Screening Test (SAST-10) from baseline to Week 52 compared with placebo [Time frame: From baseline to Week 52]
• - Mean change on Functional Rating Scale of Symptoms of Dementia (FRSSD) from baseline to Week 52 compared with placebo. [Time frame: From baseline to Week 52]
• - Mean change on Alzheimer's Disease Cooperative Study - Activities of Daily Living Scale for use in Mild Cognitive Impairment (ADCS-MCI-ADL) from baseline to Week 52 compared with placebo. [Time frame: From baseline to Week 52.]
• - Mean change on Quality of life in Alzheimer's disease (QoL-AD) from baseline to Week 52 compared with placebo. [Time frame: From baseline to Week 52.]
• - Mean change on - Pittsburgh Sleep Quality Index (PSQI) from baseline to Week 52 compared with placebo. [Time frame: From baseline to Week 52.]
• - Mean change in LDL-C mg/dL cholesterol from baseline to Week 52 compared with placebo. [Time frame: From baseline to Week 52]
• - Mean change in HDL-C mg/dL cholesterol from baseline to Week 52 compared with placebo. [Time frame: From baseline to Week 52]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Prevention

Study locations

Greece · 1 center

• Palliative Care Centre "Panagia Glykofilousa", Greek Association of Alzheimer's Disease an — Thessaloniki

Identifiers

NCT: NCT07672938 · 107/12-3-2025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗