High-fat Challenge Induced Trained Innate Immunity (SHAKE Study)

NCT05682456 | Completed

• 2 other identifiers: 107808NTR7612
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this randomized controlled cross-over trial is to investigate whether a single high-fat challenge can induce trained innate immunity in healthy volunteers. The main question it aims to answer is: Can a single high-fat challenge induce a persistent pro-inflammatory and pro-atherogenic monocyte phenotype, as detected by an augmented cytokine production capacity? To study this, participants will receive an oral high-fat and reference shake in a cross-over design and blood will be drawn before and at 1, 2, 4, 6, 24, and 72 hours after the shakes.

Conditions

Cardiovascular Diseases

Outcome Measures

Primary Outcomes (1)

• Monocyte TNFα production upon ex vivo stimulation with LPS

  72 hours

Secondary Outcomes (4)

• The monocyte production of TNFa, IL-6, IL-1beta, IL-10 upon ex vivo stimulation with LPS, Pam3Cys or Candida Albicans.

  0 hour, 4 hours, 24 hours and 72 hours

• The monocyte's inflammatory phenotype as assessed by flowcytometry analysis (i.e. membrane expression of markers including but not limited to CD14, CD16, CD11b, CCR2)

  0 hour, 4 hours, 24 hours and 72 hours

• Postprandial serum-induced TNFa and IL-6 production of healthy human monocytes upon stimulation with LPS or Pam3Cys 6 days later.

  0 hour, 2 hours, 4 hours , 6 hours

• Plasma triglyceride, glucose, free fatty acid and insulin concentrations

  0 hour, 1 hour, 2 hours, 4 hours , 6 hours

Study Arms (2)

High-fat shake

EXPERIMENTAL

Dietary Supplement: High-fat shake

Reference shake

ACTIVE COMPARATOR

Dietary Supplement: Reference shake

Interventions

High-fat shake DIETARY_SUPPLEMENT

The high-fat shake consisted of 53% (w/v) fresh cream, 3% (w/v) sugar and 44% (w/v) water

High-fat shake

Reference shake DIETARY_SUPPLEMENT

The reference shake consisted of 43% (w/v) full cream milk, 48% (w/v) full cream yoghurt, 4% (w/v) lemonade, 4% (w/v) fantomalt (Nutricia B.V., the Netherlands) and 1% (w/v) wheat fiber

Reference shake

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• LDL cholesterol \< 3.5 mmol/l, fasting triglycerides \< 2 mmol/l
• No previous cardiovascular events

You may not qualify if:

• Smoking within the year before study entry
• Diagnosed with any long-term medical condition that can interfere with the study (i.e.
• gallbladder disease, renal failure, cardiovascular disease, diabetes, rheumatoid arthritis etc.)
• Medication (with the exception of oral contraceptives) or supplement use (i.e. omega3)
• BMI \< 18 or \> 27 kg/m2
• Previous vaccination within 3 months prior to study entry
• Current infection or clinically significant infections within 1 month before study entry (defined as fever \> 38.5°C)
• Allergic to cow milk/dairy products
• Pregnancy/lactation
• Abuse of drugs or alcohol
• Vegetarian diet

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Radboudumc

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

MeSH Terms

Conditions

Cardiovascular Diseases

Study Officials

• Niels Riksen, MD, PhD

  Vascular Internal Medicine, Radboudumc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2022
• First Posted: January 12, 2023
• Study Start: May 6, 2019
• Primary Completion: January 9, 2020
• Study Completion: October 15, 2021
• Last Updated: January 12, 2023

Record last verified: 2022-12

Locations

NL (1)