Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04559828 |
| Other study ID # |
20191185 ORIVA |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
June 10, 2020 |
| Est. completion date |
July 28, 2021 |
Study information
| Verified date |
August 2021 |
| Source |
National Research Council, Spain |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Alzheimer's disease (AD) is the most common cause of dementia and its prevalence will
multiply in the coming years, so it is urgent to establish preventive and therapeutic
measures. AD it is characterized by cerebrovascular and parenchymal accumulation of protein
deposits enriched in amyloid-beta (Aβ) as a consequence of alterations of the blood-brain
barrier. More than 60% of plasma Aβ is associated with triglyceride-rich lipoproteins (TRL),
being higher in subjects with AD. Microglia act as resident macrophages and play a crucial
role in most neuropathologies, since it is activated after homeostasis impairment in the
brain, and surrounds amyloid plaques in patients with AD. As a result of microglial
activation, a large number of pro-inflammatory markers are released, mediated by alterations
in the redox state, through the generation of ROS by the complex NADPH oxidase.
In a previous study, the investigators demonstrated in BV-2 cells that artificial TRL are
capable of activating microglia and trigger an inflammatory process. In addition, the
investigators showed that some of lipophilic minor components of pomace olive oil
simultaneously modulate oxidative stress and the inflammatory response in microglia. The
investigators suggested that these results should be replicated in humans after consumption
of pomace olive oil.
Therefore, in the present study we formulate the hypothesis that human TRL are capable of
activating microglia and that such activation can be attenuated when those particles are
generated after consumption of pomace olive oil. The results of the study would lay the
foundation for the start of clinical trials demonstrating the effect of pomace oil in
reducing the risk of development and progression of AD.
Description:
In a previous study, the investigators demonstrated that triglyceride-rich lipoproteins
(TRL), which transport dietary lipid components, are able of activating microglia, which
could be associated with the state of neuroinflammation in patients of Alzheimer's disease.
In addition, the investigators also demonstrated that some of the minor fat-soluble
components of olive pomace oil simultaneously modulate oxidative stress and the inflammatory
response in microglia, so that these components could have the ability to protect the brain
from microglial overactivation when transported in TRL.
In that study, the investigators used artificial TRL that were manufactured ad-hoc in the
laboratory, in order to be able to test the effect of the compounds both individually and
together. Now is the time to consolidate the results using human TRL, obtained after the
consumption of olive pomace oil. The investigators expect that the results of this study will
reveal that the intake of olive pomace oil can prevent the release of inflammatory markers
caused by the overactivation of microglia, which could be associated to a reduction in the
risk of development and progression of Alzheimer's disease.
Objectives and design
To test this hypothesis, two specific objectives will be addressed:
1. To obtain and characterize human TRL obtained after the intake of olive pomace oil.
2. To evaluate the mitigating effect of the microglial activation by TRL obtained after the
intake of olive pomace oil.
The study has been designed as a randomized and crossover trial in the postprandial phase in
healthy subjects, which will be divided into two groups to which a pomace oil and high-oleic
sunflower oil will be administered.
Activities
The specific objectives set out in the project will be addressed through the execution of the
activities that are detailed below:
1. Selection of volunteers and administration of olive pomace oil. 1.1. Obtaining and
characterizing the experimental oils. 1.2. Recruitment and selection of volunteers. 1.3.
Clinical trial in the postprandial phase.
2. Isolation and characterization of human TRL. 2.1. General determinations in blood serum.
2.2. Characterization of TRL.
3. Microglial activation in cells treated with human TRL. 3.1. Assays in cell cultures.
3.2. Analytical determinations. 3.3. Data processing and reporting.
