- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05746013
Lipoproteins and ImmunoMetabolism
February 16, 2023 updated by: Sergio Montserrat de la Paz, University of Seville
Deciphering the Role of Dietary Fatty Acids on HDL Functionality
Dietary interventions have been consistently proposed as a part of a comprehensive strategy to lower the incidence and severity of atherosclerosis and cardiovascular diseases (CVD).
Excessive consumption of fats enriched in saturated fatty acids (SFA) is associated with an increased risk of atherosclerosis and other CVD.
By contrast, replacement of SFA with monounsaturated fatty acids (MUFA) and omega-3 long-chain polyunsaturated fatty acids (ω-3 PUFA) has been reported to be inversely associated with risk of atherosclerosis.
This is partly due to the ability of MUFA (and PUFA) in modulating low-density lipoprotein (LDL) and triglyceride-rich lipoprotein (TRL) lipid composition and oxidation status, and thereby the functionality of such lipoproteins.
While most of the nutritional studies have focused on elucidating the mechanisms by which dietary fats affect LDL and TRL, little or nothing is known about the regulatory effect of MUFA and PUFA on structure and functional remodelling of high-density lipoproteins (HDL).
There is clear evidence of an inverse association between plasma levels of HDL and the formation of atherosclerotic plaques.
However, recent studies have suggested that HDL may not be as beneficial as thought at least in patients with established cardiometabolic disorders.
In those patients, the HDL behaves as pro-inflammatory lipoproteins.
Until now, few studies have addressed this "dark side" of HDL and has never been evaluated the role of dietary fatty acids on HDL plasticity (i.e.
phenotype and functionality).
A better understanding of this duality between anti-inflammatory and pro-inflammatory HDL would be relevant to prevent HDL-related atherogenic dyslipidemias and to provide personalized dietary advices for a successful management of atherogenic lipid profiles.
This step of proof-of-principle will determine the instrumental role of major fatty acids present on a diet (SFA, MUFA and MUFA plus ω-3 PUFA) in promoting or reversing the phenotype of pro-inflammatory HDL.
We expect to offer a novel insight on HDL and its relationship with dietary fatty acids through the following objectives: 1) To analyse acute changes in the lipidome, proteome and functional properties of HDL in humans (healthy volunteers and patients with metabolic syndrome) upon a challenge of a meal rich in SFA, MUFA or MUFA plus ω-3 PUFA; and 2) To analyse the influence of diets rich in SFA, MUFA and MUFA plus ω-3 PUFA on HDL plasticity in a preclinical animal model of diet-induced metabolic syndrome and that develops atherosclerosis.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
40
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Seville, Spain, 41009
- University of Seville
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
Male
Description
Inclusion Criteria:
- clinical diagnosis of metabolic syndrome
Exclusion Criteria:
- Allergy to dairy products
- Allergy to fish oil
- Vegetarian
- Tobacco smoker
- Current or recent (<4 wk) use of fish oil supplements or more than four times fish/week
- Received innoculations within 2 mo of starting the study or planned to during the study
- Donated or intended to donate blood from 2 mo before the study till 2 mo after the study
- Unstable body weight (no weight gain/loss >3 kg)
- Medical condition that can interfere with the study outcome (i.e., biochemical evidence of active heart disease, renal impairment, hypothyroidism, liver dysfunction, etc.)
- Use of medications know to interfere with glucose homeostasis or lipid metabolism
- Use of anti-inflammatory medication, hormone or cytokine or growth factor therapies
- Abuse of drugs and/or alcohol
- Participation in another biomedical study within 1 mo before the first screening visit, or not wanting to be informed about chance-findings during screening.
- Severe diabetes, which requires application of insuin
- Diabetes-related complications.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: No Fat meal
|
The oral lipid emulsions will contain water, sucrose, emulsifier, flavouring, and the corresponding fat (50 g/m2 of body surface area): milk cream (SFA) or refined olive oil (MUFA) with or without a dose of omega-3 PUFA, which will consist of 920 mg of EPA and 760 mg of DHA.
|
Experimental: SFA meal
|
The oral lipid emulsions will contain water, sucrose, emulsifier, flavouring, and the corresponding fat (50 g/m2 of body surface area): milk cream (SFA) or refined olive oil (MUFA) with or without a dose of omega-3 PUFA, which will consist of 920 mg of EPA and 760 mg of DHA.
|
Experimental: MUFA meal
|
The oral lipid emulsions will contain water, sucrose, emulsifier, flavouring, and the corresponding fat (50 g/m2 of body surface area): milk cream (SFA) or refined olive oil (MUFA) with or without a dose of omega-3 PUFA, which will consist of 920 mg of EPA and 760 mg of DHA.
|
Experimental: PUFA meal
|
The oral lipid emulsions will contain water, sucrose, emulsifier, flavouring, and the corresponding fat (50 g/m2 of body surface area): milk cream (SFA) or refined olive oil (MUFA) with or without a dose of omega-3 PUFA, which will consist of 920 mg of EPA and 760 mg of DHA.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Evolution of Glucose levels in postprandial state.
Time Frame: Up to 6 hours
|
Blood glucose levels, measured by biochemical procedures (mg/dL).
|
Up to 6 hours
|
Evolution of Insulin in postprandial state.
Time Frame: Up to 6 hours
|
Blood Insulin levels, measured using ELISA procedures (pmol/L).
|
Up to 6 hours
|
Evolution of C-peptide in postprandial state
Time Frame: Up to 6 hours
|
C-peptide, using routine biochemical procedures (pmol/L).
|
Up to 6 hours
|
Evolution of Trigliceride and NEFA parameters in postprandial state
Time Frame: Up to 6 hours
|
Triglyceride and NEFA levels in plasma will be measured at several time-points postprandially using routine biochemical procedures (mg/dL)
|
Up to 6 hours
|
Evolution of NAMPT in postprandial state
Time Frame: Up to 6 hours
|
NAMP activity will be measured in plasma at several postprandial time-points using colorimetric techniques (UI/ml).
|
Up to 6 hours
|
Evolution of cytokines in postprandial state
Time Frame: Up to 6 hours
|
Pro-inflammatory and anti-inflammatory cytokines, including NFα, IL-1β, IL-6, IL-8, IL-10, ICAM-1, MCP-1, leptin, and adiponectin, in plasma will be measured using ELISA techniques (mg/dl).
|
Up to 6 hours
|
Evolution of inflammatory markers in postprandial state.
Time Frame: Up to 6 hours
|
The acute phase protein (hsCRP), PAI-1, fibrinogen, transferrin, albumin, and myeloperoxidase (MPO) will be measured using colorimetric techniques (mg/dl).
|
Up to 6 hours
|
HDL lipoproteome
Time Frame: Up to 6 hours.
|
HDL protein and lipid fractions HDL will be analysed by MALDI-TOF MS after employing an organic polymeric anion exchanger [Poly(GMA/EGDMA)] for lipoprotein enrichment from serum samples.
|
Up to 6 hours.
|
HDL antioxidant capacity
Time Frame: Up to 6 hours.
|
HDL obtained from different postprandial points will be tested by their capacity to prevent LDL oxidation with an in vitro cell-free assay.
|
Up to 6 hours.
|
HDL cholesterol efflux capacity
Time Frame: Up to 6 hours.
|
HDL cholesterol efflux capacity will be measured using fluorescent-labelled cholesterol.
HDL extracted from serum at different postprandial points will be tested.
|
Up to 6 hours.
|
HDL LCAT activity
Time Frame: Up to 6 hours.
|
Lecithin choltesteryl acyl transferase (LCAT) activity (UI/ml) of HDL obtained from different postprandial points will be measured using a fluorimetric cell-free assay.
|
Up to 6 hours.
|
HDL PON1 activity
Time Frame: Up to 6 hours
|
Paraoxonse 1 (PON1) activity, of HDL obtained from serum at different postprandial tiems, will be measured using a colorimetric assay (pmol/mL).
|
Up to 6 hours
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 1, 2020
Primary Completion (Anticipated)
May 1, 2023
Study Completion (Anticipated)
December 1, 2025
Study Registration Dates
First Submitted
November 17, 2022
First Submitted That Met QC Criteria
February 16, 2023
First Posted (Estimate)
February 27, 2023
Study Record Updates
Last Update Posted (Estimate)
February 27, 2023
Last Update Submitted That Met QC Criteria
February 16, 2023
Last Verified
November 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- US-1263458
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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