Alzheimer s DiseaseNEUROLEANCT07847944
Neuroprotective Effects of Oleanolic Acid and Erythrodiol in Prodromal Alzheimer's Disease
A study testing Oleanolic acid-enriched olive oil, Pomace olive oil and Commercial olive oil 0.4 degrees in people with Alzheimer s Disease and Prodromal Alzheimer's Disease, run by Spanish National Research Council at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 80 years
- Conditions the study is for
- Alzheimer s Disease, Prodromal Alzheimer's Disease
- What is being tested?
- Oleanolic acid-enriched olive oil, Pomace olive oil and Commercial olive oil 0.4 degrees
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteSpain
- Study dates
- Jan 2027to Jan 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 50 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Spain1 site
Instituto de la Grasa, CSIC
Seville, 41013
Elena M Yubero-Serrano, PhD., +34687848695, elena.yubero@ig.csic.es
About this study
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.
Read more
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.
Read the detailed description
NEUROLEA is a multicenter, randomized, double-blind, controlled dietary intervention trial coordinated by the Instituto de la Grasa (CSIC). Participants will be recruited at the Neurology Units of Hospital Universitario Virgen del Rocío, Hospital Universitario Reina Sofía and Hospital Universitario de Valme.
Study oils. High-purity crystalline oleanolic acid (>95%) will be obtained from olive leaves following a procedure developed by the research team (Spanish Patent ES2160553) and used to prepare an oleanolic acid-enriched olive oil (600 mg/kg) according to European Patent EP18382510. A commercial olive oil 0.4° will serve as the control oil, as it has the same fatty acid composition as the other oils but a very low content of minor bioactive components. Pomace olive oil, which naturally contains oleanolic acid and erythrodiol, will be purchased from local markets. Oil composition will be verified by gas chromatography and differential scanning calorimetry before the intervention begins.
Randomization and blinding. Allocation will follow computer-generated random numbers prepared by the trial coordinator. Participants, clinical and nutritional research staff, and the neuropsychologists scoring the cognitive assessments will be blinded to group assignment.
Sample size. Thirty-four participants per arm are required for 90% power to detect a 10% reduction in dementia incidence in the functional oil arms compared with a 25% incidence in the control arm over 12 months (alpha 0.05). Allowing for up to 15% attrition in a long-term dietary intervention, the target is 40 participants per arm (120 in total).
Intervention and follow-up. Participants will consume 55 mL/day of the assigned oil, preferably raw and distributed across the three main meals, for 12 months. Adherence will be assessed with the self-reported Haynes-Sackett compliance test and by return of empty bottles, methods previously used by this team in the PREDIABOLE and OLTRAD trials. Participants and their caregivers will receive general healthy-eating guidance throughout the study.
Assessments. Evaluations will be performed at baseline and after 6 and 12 months, and will include a comprehensive neuropsychological battery, clinical examination, anthropometry and body composition by bioimpedance, dietary intake and diet quality questionnaires, and fasting blood and urine sampling. Serum concentrations of oleanolic acid and erythrodiol will be measured by HPLC-MS to verify exposure.
Mechanistic analyses. Beyond the clinical endpoints, the trial will examine circulating markers of lipid and glucose metabolism, oxidative stress and inflammation, and advanced glycation end product metabolism, together with the expression of related genes in peripheral blood mononuclear cells. Blood-based markers of Alzheimer's disease pathology (p-tau 217, neurofilament light chain, glial fibrillary acidic protein, and the amyloid beta 42/40 ratio) will be quantified at baseline and 12 months.
Data will be managed in REDCap and stored in pseudonymized form in accordance with the General Data Protection Regulation.
- Conditions
- Alzheimer s Disease, Prodromal Alzheimer's Disease
- Being tested
- Oleanolic acid-enriched olive oil, Pomace olive oil, Commercial olive oil 0.4 degrees
- Keywords
- Oleanolic acid, Erythrodiol, Triterpenes, Olive oil, Dietary intervention, Neuroprotection, Advanced glycation end products, Functional Foods, Oxidative stress
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oleanolic acid-enriched olive oilDietary 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.
Pomace olive oilDietary 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.
Commercial olive oil 0.4 degreesDietary 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Dietary Supplement: Commercial olive oil 0.4 degrees |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline to 12-months
Secondary outcomes (4)
Change in Clinical Dementia Rating Sum of Boxes (CDR-SB)
CDR-SB total score ranges from 0 to 18, with higher scores indicating more severe cognitive impairment.
Measured: Baseline to 12-months
Change in Mini-Mental State Examination (MMSE) score
MMSE total score ranges from 0 to 30, with higher scores indicating better global cognitive performance
Measured: Baseline to 12-months
Change in Mild Behavioral Impairment Checklist (MBI-C) score
MBI-C assesses behavioral and psychological symptoms; higher scores indicate more severe symptoms
Measured: Baseline to 12-months
Change in Functional Activities Questionnaire (FAQ) score
FAQ total score ranges from 0 to 30, with higher scores indicating greater functional impairment
Measured: Baseline to 12-months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2026
- Study startJan 2027 (estimated)
- Primary completionOct 2028 (estimated)
- Study completionJan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer s DiseaseStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Spanish National Research Council
- Sponsor type
- Other government
- Collaborators
- Valme University Hospital, Universidad de Granada, Maimónides Biomedical Research Institute of Córdoba, Hospital Universitario Reina Sofia de Cordoba, Universidad Pablo de Olavide
- Responsible party
- Principal investigator, Elena M. Yubero-Serrano, Instituto de la Grasa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07847944
- Sponsor's protocol ID
- PID2024-161189OB-I00
- Acronym
- NEUROLEA
- Status last verified
- Sep 2026
- First submitted
- 22 Sep 2026
- Last updated
- 29 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data underlying published results will be made available in institutional repositories, in accordance with the data management plan of the project and with international standards for the documentation of clinical study data.
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuroprotective Effects of Oleanolic Acid and Erythrodiol in Prodromal Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT07847944
- Acronym / sponsor ID
- NEUROLEA / PID2024-161189OB-I00
- Conditions
- Alzheimer s Disease, Prodromal Alzheimer's Disease
- Keywords
- Oleanolic acid, Erythrodiol, Triterpenes, Olive oil, Dietary intervention, Neuroprotection, Advanced glycation end products, Functional Foods
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Spanish National Research CouncilOther government
- Collaborators
- Valme University Hospital, Universidad de Granada, Maimónides Biomedical Research Institute of Córdoba, Hospital Universitario Reina Sofia de Cordoba, Universidad Pablo de Olavide
- Study start
- Jan 2027 (estimated)
- Primary completion
- Oct 2028 (estimated)
- Study completion
- Jan 2029 (estimated)
- First posted
- 29 Sep 2026 (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.
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.
Detailed description
NEUROLEA is a multicenter, randomized, double-blind, controlled dietary intervention trial coordinated by the Instituto de la Grasa (CSIC). Participants will be recruited at the Neurology Units of Hospital Universitario Virgen del Rocío, Hospital Universitario Reina Sofía and Hospital Universitario de Valme.
Study oils. High-purity crystalline oleanolic acid (>95%) will be obtained from olive leaves following a procedure developed by the research team (Spanish Patent ES2160553) and used to prepare an oleanolic acid-enriched olive oil (600 mg/kg) according to European Patent EP18382510. A commercial olive oil 0.4° will serve as the control oil, as it has the same fatty acid composition as the other oils but a very low content of minor bioactive components. Pomace olive oil, which naturally contains oleanolic acid and erythrodiol, will be purchased from local markets. Oil composition will be verified by gas chromatography and differential scanning calorimetry before the intervention begins.
Randomization and blinding. Allocation will follow computer-generated random numbers prepared by the trial coordinator. Participants, clinical and nutritional research staff, and the neuropsychologists scoring the cognitive assessments will be blinded to group assignment.
Sample size. Thirty-four participants per arm are required for 90% power to detect a 10% reduction in dementia incidence in the functional oil arms compared with a 25% incidence in the control arm over 12 months (alpha 0.05). Allowing for up to 15% attrition in a long-term dietary intervention, the target is 40 participants per arm (120 in total).
Intervention and follow-up. Participants will consume 55 mL/day of the assigned oil, preferably raw and distributed across the three main meals, for 12 months. Adherence will be assessed with the self-reported Haynes-Sackett compliance test and by return of empty bottles, methods previously used by this team in the PREDIABOLE and OLTRAD trials. Participants and their caregivers will receive general healthy-eating guidance throughout the study.
Assessments. Evaluations will be performed at baseline and after 6 and 12 months, and will include a comprehensive neuropsychological battery, clinical examination, anthropometry and body composition by bioimpedance, dietary intake and diet quality questionnaires, and fasting blood and urine sampling. Serum concentrations of oleanolic acid and erythrodiol will be measured by HPLC-MS to verify exposure.
Mechanistic analyses. Beyond the clinical endpoints, the trial will examine circulating markers of lipid and glucose metabolism, oxidative stress and inflammation, and advanced glycation end product metabolism, together with the expression of related genes in peripheral blood mononuclear cells. Blood-based markers of Alzheimer's disease pathology (p-tau 217, neurofilament light chain, glial fibrillary acidic protein, and the amyloid beta 42/40 ratio) will be quantified at baseline and 12 months.
Data will be managed in REDCap and stored in pseudonymized form in accordance with the General Data Protection Regulation.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| OA-enriched Olive Oil | Experimental | Dietary Supplement: Oleanolic acid-enriched olive oilParticipants 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. |
| Pomace Olive Oil | Experimental | Dietary Supplement: Pomace olive oilParticipants 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. |
| Control Olive Oil | Placebo comparator | Dietary Supplement: Commercial olive oil 0.4 degreesParticipants 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. |
Who may qualify
- Ages
- 50 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (1 listed)
- 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
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 |
|---|---|---|
| Oleanolic acid-enriched olive oilOlive oil enriched with oleanolic acid (600 mg/kg), 55 mL/day for 12 months, consumed preferably raw and distributed across the three main meals. | Dietary supplement | OA-enriched Olive Oil |
| Pomace olive oilCommercial 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. | Dietary supplement | Pomace Olive Oil |
| Commercial olive oil 0.4 degreesCommercial 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. | Dietary supplement | Control Olive Oil |
Primary outcome
Conversion from prodromal Alzheimer's disease to dementia
Time frame: Baseline to 12-months
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
4 secondary outcomes
Change in Clinical Dementia Rating Sum of Boxes (CDR-SB)
Time frame: Baseline to 12-months
Change in Mini-Mental State Examination (MMSE) score
Time frame: Baseline to 12-months
Change in Mild Behavioral Impairment Checklist (MBI-C) score
Time frame: Baseline to 12-months
Change in Functional Activities Questionnaire (FAQ) score
Time frame: Baseline to 12-months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2026.
- Individual participant dataSharing planned: Yes. De-identified individual participant data underlying published results will be made available in institutional repositories, in accordance with the data management plan of the project and with international standards for the documentation of clinical study data.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Oleanolic acid-enriched olive oil, Pomace olive oil and Commercial olive oil 0.4 degrees in people with Alzheimer s Disease and Prodromal Alzheimer's Disease, run by Spanish National Research Council 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 1 inclusion and 1 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: opening soon, as of the sponsor's last update on 29 Sep 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Elena M Yubero-Serrano, PhD. (+34687848695, elena.yubero@ig.csic.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Conversion from prodromal Alzheimer's disease to dementia (time frame: Baseline to 12-months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Sep 2026.