Neuroprotective Effects of Oleanolic Acid and Erythrodiol in Prodromal Alzheimer's Disease

NCT07847944 | Not Yet Recruiting DMC

• 1 other identifier: PID2024-161189OB-I00
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Alzheimer's disease begins many years before memory problems become obvious. People in the early ("prodromal") stage have memory complaints but are still independent in daily life. At present there is no treatment that prevents this stage from progressing to dementia. Olive oil contains two natural compounds, oleanolic acid and erythrodiol. Earlier work by this research team suggests that these compounds may reduce inflammation and oxidative stress and may improve the way the body handles sugars and fats, processes that are also altered in Alzheimer's disease. This study will test whether consuming olive oils that contain these compounds delays the progression from prodromal Alzheimer's disease to dementia. A total of 120 adults aged 50 to 80 years with prodromal Alzheimer's disease will take part at three public hospitals in southern Spain. Participants will be assigned by chance to one of three groups and will consume 55 mL per day of one of three oils for 12 months: olive oil enriched with oleanolic acid, pomace olive oil (which naturally contains both compounds), or a standard commercial olive oil with very low levels of these compounds. Neither the participants nor the staff assessing them will know which oil each person is receiving. Participants will attend study visits at the start of the study and after 6 and 12 months. At these visits they will complete memory and thinking tests, a physical and nutritional assessment, and blood and urine tests.

Conditions

Alzheimer s Disease; Prodromal Alzheimer's Disease

Keywords

Oleanolic acid; Erythrodiol; Triterpenes; Olive oil; Dietary intervention; Neuroprotection; Advanced glycation end products; Functional Foods; Oxidative stress

Outcome Measures

Primary Outcomes (1)

• Conversion from prodromal Alzheimer's disease to dementia

  Proportion of participants converting to dementia, defined as a change in the Clinical Dementia Rating Global Score (CDR-GS) from 0.5 at baseline to 1 or higher. The CDR-GS ranges from 0 to 3, with higher scores indicating greater dementia severity

  Baseline to 12-months

Secondary Outcomes (4)

• Change in Clinical Dementia Rating Sum of Boxes (CDR-SB)

  Baseline to 12-months

• Change in Mini-Mental State Examination (MMSE) score

  Baseline to 12-months

• Change in Mild Behavioral Impairment Checklist (MBI-C) score

  Baseline to 12-months

• Change in Functional Activities Questionnaire (FAQ) score

  Baseline to 12-months

Other Outcomes (8)

• Change in lipid metabolism biomarkers

  Baseline, 6 months and 12 months

• Change in glucose metabolism and insulin sensitivity biomarkers

  Baseline, 6 months and 12 months

• Change in plasma lipid classes

  Baseline and 12 months

Study Arms (3)

OA-enriched Olive Oil

EXPERIMENTAL

Participants will consume 55 mL/day of olive oil enriched with oleanolic acid (600 mg/kg) for 12 months, preferably raw and distributed across the three main meals.

Dietary Supplement: Oleanolic acid-enriched olive oil

Pomace Olive Oil

EXPERIMENTAL

Participants will consume 55 mL/day of commercial pomace olive oil, which naturally contains oleanolic acid (180 mg/kg) and erythrodiol (670 mg/kg), for 12 months, preferably raw and distributed across the three main meals.

Dietary Supplement: Pomace olive oil

Control Olive Oil

PLACEBO COMPARATOR

Participants will consume 55 mL/day of commercial olive oil 0.4°, which has the same fatty acid composition but a very low content of minor bioactive components, for 12 months, preferably raw and distributed across the three main meals.

Dietary Supplement: Commercial olive oil 0.4 degrees

Interventions

Oleanolic acid-enriched olive oil DIETARY_SUPPLEMENT

Olive oil enriched with oleanolic acid (600 mg/kg), 55 mL/day for 12 months, consumed preferably raw and distributed across the three main meals.

OA-enriched Olive Oil

Pomace olive oil DIETARY_SUPPLEMENT

Commercial pomace olive oil, naturally containing oleanolic acid (180 mg/kg) and erythrodiol (670 mg/kg), 55 mL/day for 12 months, consumed preferably raw and distributed across the three main meals.

Pomace Olive Oil

Commercial olive oil 0.4 degrees DIETARY_SUPPLEMENT

Commercial olive oil 0.4°, with the same fatty acid composition but a very low content of minor bioactive components, 55 mL/day for 12 months, consumed preferably raw and distributed across the three main meals.

Control Olive Oil

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women aged 50 to 80 years Diagnosis of prodromal Alzheimer's disease, meeting all of the following: memory complaints corroborated by a reliable informant; Mini-Mental State Examination (MMSE) total score between 22 and 30; Free and Cued Selective Reminding Test (FCSRT, picture version) total recall score of 46 or less; Clinical Dementia Rating Global Score (CDR-GS) of 0.5; functional independence in activities of daily living (Functional Activities Questionnaire total score of 8 or less); plasma p-tau 217 above 0.45 pg/mL measured by the Lumipulse method Ability and willingness to attend scheduled visits at the study center Adequate visual and auditory capacity to complete study evaluations Educational level sufficient to read and write Written informed consent

You may not qualify if:

• Absence of a reliable informant Evidence, based on medical history or clinical evaluation, of a neurological condition other than Alzheimer's disease that could account for the cognitive impairment Clinically significant, advanced or unstable systemic disease that may interfere with cognitive evaluation Severe psychiatric disorders, including schizophrenia, bipolar disorder or active major depression History of alcohol or psychotropic substance abuse Pre-existing intellectual disability that precludes neuropsychological evaluation

Sponsors & Collaborators

• Spanish National Research Council: lead
• Universidad de Granada: collaborator
• Hospital Universitario Reina Sofia de Cordoba: collaborator
• Valme University Hospital: collaborator
• Maimónides Biomedical Research Institute of Córdoba: collaborator
• Universidad Pablo de Olavide: collaborator

Study Sites (1)

Instituto de la Grasa, CSIC

Seville, 41013, Spain

Location

Central Study Contacts

Elena M Yubero-Serrano, PhD.

CONTACT

+34687848695; elena.yubero@ig.csic.es

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Scientist

Study Record Dates

• First Submitted: September 22, 2026
• First Posted: September 29, 2026
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: September 29, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Data will become available after completion of the project and publication of the main results, and will remain accessible for at least five years thereafter.
• Access Criteria: Requests for access should be submitted to the principal investigator by e-mail, including a description of the proposed research question and analysis plan. Requests will be evaluated by the study investigators. Access to de-identified individual participant data and to the supporting documents will be granted to researchers whose proposal is considered methodologically sound and consistent with the consent given by study participants, subject to a signed data access agreement.

Locations

ES (1)