Modulating Immune Responses After Consistent Lipid Exposure

NCT07502898 | Recruiting

• 1 other identifier: NL009718
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

Background of the study: Enhanced immune responses can lead to chronic hyperinflammation, which contributes to the development of non-communicable diseases such as type 2 diabetes and cardiovascular disease. Poor dietary habits, particularly the consumption of high-fat meals, are thought to trigger this process by increasing the concentration of triglyceride-rich lipoproteins in the bloodstream, resulting in postprandial triglyceridemia. This state stimulates immune cell activation, elevates circulating lipopolysaccharide levels, and enhances the production of inflammatory mediators including IL-6, TNFα, VCAM1, and ICAM1, as well as changes in inflammatory gene expression in peripheral blood mononuclear cells. Until now, most research investigating the relationship between fat intake and postprandial inflammation has focused on the effects of a single high-fat meal. However, in daily life, individuals typically spend the majority of the day-up to 18 hours-in a postprandial state, continuously exposed to multiple meals containing a mix of macronutrients and fats from diverse sources. It remains unclear how repeated fat intake influences the timing, magnitude, and overall pattern of the postprandial immune response. The MIRACLE study is designed to address this gap by exploring how repetitive postprandial fat exposure affects circulating immune cells in healthy individuals, comparing the effects of plant-derived and dairy-derived lipids. The study employs a double-blind, randomized, cross-over, two-armed intervention design in which each participant acts as their own control. Objective of the study: The primary objective of the MIRACLE study is to determine how daily repetitive exposure to lipids from the same source modulates the postprandial immune response, as reflected by IL-6 levels, compared with acute exposure. Postprandial IL-6 concentrations will be measured using multiplex ELISA assays at multiple time points following the high-fat shake at baseline (T0) and after repeated exposure (T1). These data will allow calculation of protein dynamics and incremental area under the curve (iAUC) values for IL-6. Secondary objectives: Secondary objectives include comparing postprandial IL-6 iAUC values across T0, T1, and T2; comparing IL-6 responses between the plant- and dairy-derived fats; and identifying mechanisms underlying lipid-induced immunomodulation in PBMCs, including changes in immune cell functioning, phenotypes, and circulating inflammatory parameters. The study will also assess the effects of repeated fat intake on postprandial metabolic markers such as glucose and triglyceride levels. Glucose will be continuously monitored using glucose sensors, while other metabolic parameters will be measured in plasma. Additionally, the relationship between body composition, as assessed by Dual Energy X-ray Absorptiometry (DXA), and postprandial immune and metabolic responses will be evaluated at T0, T1, and T2. Study design: On each test day, a catheter cannula will be inserted into an antecubital vein, followed by a 30-minute rest period before measurements begin. Baseline blood samples (t = 0) will be drawn from the catheter, after which participants consume a 0.6 L high-fat shake containing 95 grams of fat from one of the two lipid sources. Subsequent blood samples will be collected at 0.5, 1, 2, 3, 4, and 6 hours post-consumption to monitor postprandial responses. Following the first test day, participants will consume smaller breakfast shakes (\~300 mL, \~20 grams of fat) daily for four consecutive weeks, using lipid powders corresponding to the same fat source. After these four weeks, the postprandial test day will be repeated following the same procedures as on the first day. After the second test day, a washout period of two weeks will take place before participants return for a third test day, again following the same protocol. This will be followed by another washout period of two weeks to three months before beginning the second arm of the study, during which participants will consume lipids from the alternate fat source. Thus, each participant completes both the plant-derived and dairy-derived fat interventions in a randomized order, ensuring within-subject comparison. Study population: 39 healthy male or female volunteers, age 40-70, BMI 22-27. Intervention: 2 different breakfast shakes based on either plant-derived or dairy-derived fat.

Conditions

Lipid Metabolism; Postprandial Inflammation

Outcome Measures

Primary Outcomes (1)

• Postprandial IL-6 plasma levels in response to a high fat shake before and after the 4-week intervention period.

  The main objective is to establish the impact of daily repetitive exposure (after a 4-week intervention period) to lipids from the same lipid source on the postprandial immune response reflected by circulating IL-6 levels, compared to the effects of acute exposure (before a 4-week intervention period) using two different lipid sources in healthy middle-aged men and women. Therefore, we will measure: Postprandial IL-6 levels in the circulation in response to a high fat shake measured as part of a multiplex ELISA assay before and after the 4-week intervention period. By measuring baseline levels and levels at all postprandial sampling time points, we will be able to determine protein dynamics and iAUCs of these cytokines. As we will determine cytokine levels in response to the same high fat shake before and after the 4-week intervention period, we will be able to define whether repetitive intake of fat from the same source alters the postprandial immune response.

  Levels will be assessed in cryopreserved plasma, derived from whole blood collected before and following a high-fat shake at baseline and up to 6 hours postprandially on the two test days per lipid source.

Secondary Outcomes (4)

• Postprandial inflammatory plasma proteins in response to a high-fat shake before the 4-week intervention phase, directly after the intervention phase, and after a two-week wash out period.

  Levels will be assessed in cryopreserved plasma, derived from whole blood collected before and following high-fat shake at baseline and up to 6 hours postprandially on all three test days per lipid source.

• Postprandial IL-6 plasma levels in response to two different high fat shakes before, directly after the 4-week intervention period and after a 2-week wash out period.

  Levels will be assessed in cryopreserved plasma, derived from whole blood collected before and following a high-fat shake at baseline and up to 6 hours postprandially on all three test days per lipid source.

• Postprandial glucose levels in response to two different high fat shakes before, directly after the 4-week intervention period and after a 2-week wash out period.

  Levels will be assessed through CGM sensors during the entire duration of the study, so during the full six weeks of both arms including all test days involving high-fat shake consumption.

• Postprandial lipid profiles in response to two different high fat shakes before, directly after the 4-week intervention period and after a 2-week wash out period.

  Lipids will be assessed in cryopreserved plasma, derived from whole blood collected before and following a high-fat shake at baseline and up to 6 hours postprandially on all three test days per lipid source.

Study Arms (2)

Dairy-derived fat shake then plant-derived fat

ACTIVE COMPARATOR

During the first dietary intervention, the breakfast will consist of a dairy-derived lipid shake. During the second dietary intervention, the breakfast will consist of a plant-derived lipid shake.

Other: Dairy-derived breakfast shake consumption; Other: Plant-derived breakfast shake consumption

Plant-derived fat shake then dairy-derived fat shake

EXPERIMENTAL

During the first dietary intervention, the breakfast will consist of a plant-derived lipid shake. During the second dietary intervention, the breakfast will consist of a dairy-derived lipid shake.

Other: Dairy-derived breakfast shake consumption; Other: Plant-derived breakfast shake consumption

Interventions

Dairy-derived breakfast shake consumption OTHER

4-week consumption of a breakfast shake containing dairy-derived lipids.

Dairy-derived fat shake then plant-derived fat; Plant-derived fat shake then dairy-derived fat shake

Plant-derived breakfast shake consumption OTHER

4-week consumption of a breakfast shake containing plant-derived lipids.

Dairy-derived fat shake then plant-derived fat; Plant-derived fat shake then dairy-derived fat shake

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Apparently healthy man or woman
• Age 40-70y at the time of screening
• BMI of 22-27 kg/m2
• Having a Hb value above 8.4 (men) or 7.4 (women) mmol/L
• Having veins suitable for blood sampling via a catheter cannula (judged by study nurse/ medical doctor)
• Willing to have dairy-based breakfast every day
• Having a mobile phone suitable for installing the research app
• Signed informed consent and able to adhere to the protocol

You may not qualify if:

• A history of cardiovascular diseases, such as a stroke or heart disease;
• Having an eating disorder;
• Having diabetes (type I or type II);
• Having used antibiotics in the past 3 months;
• Using diabetes medication;
• Using medications that may affect the study results (as assessed by the study physician);
• Suffering from stomach or intestinal problems, such as Crohn's disease, ulcerative colitis, irritable bowel syndrome, or having undergone major digestive system surgery;
• Having known food allergies or intolerances to foods used in the study (e.g., cow's milk);
• Having an Hb level of less than 8.5 mmol/L (for men) or less than 7.5 mmol/L (for women) - to be tested during the eligibility assessment;
• Being allergic or intolerant to medical skin patches;
• Suffering from chronic or acute inflammatory diseases, such as rheumatoid arthritis or psoriatic arthritis;
• Having an autoimmune disease;
• Having thyroid problems;
• Having recently donated blood (within 2 months before the eligibility assessment) or planning to donate blood during the study period;
• Having recently participated in another medical-scientific study (within 2 months before the eligibility assessment);

Sponsors & Collaborators

• Wageningen University: lead
• FrieslandCampina, Amersfoort, The Netherlands: collaborator

Study Sites (1)

Wageningen University

Wageningen, 6708WE, Netherlands

RECRUITING

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 11, 2025
• First Posted: March 31, 2026
• Study Start: January 5, 2026
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: March 31, 2026

Record last verified: 2026-01

Locations

NL (1)