Lipoproteins and ImmunoMetabolism

NCT ID: NCT05746013

Last Updated: 2023-02-27

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-01
• Study Completion Date: 2025-12-31

Brief Summary

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.

Conditions

Obesity; Metabolic Syndrome; Metabolism Disorder; Inflammation; Immune System and Related Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

No Fat meal

Group Type: PLACEBO_COMPARATOR

Lipid Emulsion

Intervention Type: DIETARY_SUPPLEMENT

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.

SFA meal

Group Type: EXPERIMENTAL

Lipid Emulsion

Intervention Type: DIETARY_SUPPLEMENT

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.

MUFA meal

Group Type: EXPERIMENTAL

Lipid Emulsion

Intervention Type: DIETARY_SUPPLEMENT

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.

PUFA meal

Group Type: EXPERIMENTAL

Lipid Emulsion

Intervention Type: DIETARY_SUPPLEMENT

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.

Interventions

Lipid Emulsion

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.

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Spanish National Research Council

OTHER_GOV

Sponsor Role: collaborator

University of Seville

OTHER

Sponsor Role: lead

Responsible Party

Sergio Montserrat de la Paz

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Seville

Seville, , Spain

Countries

Spain

Other Identifiers

US-1263458

Identifier Type: -

Identifier Source: org_study_id