GPR146 and Cholesterol Metabolism

NCT07142317 | Not Yet Recruiting

• 1 other identifier: METC 25-027
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

Blood cholesterol balance is regulated by an interplay between the small intestine and the liver. Recently, a new protein (cholesin) was discovered, which is secreted by intestinal cells after dietary cholesterol intake. Cholesin travels to the liver and binds to the GPR146 receptor. This inhibits cholesterol production in the liver. Because plant sterols lower blood cholesterol levels by reducing cholesterol absorption in the intestine, the investigators would like to understand the effects of plant sterols on GPR146. The investigator hypothesis is that the production of the GPR146 gene differs after adding plant sterols to a high-cholesterol diet compared to eating a high-cholesterol and low-cholesterol diet. The main objective of this study is to investigate whether the expression of the GPR146 gene in the blood of adults differs between three meals with different levels of cholesterol intake. The secondary objective of the study is to examine changes in the expression of cholesin, the LDL receptor (LDLR), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) genes in the blood after these meals. Furthermore, changes in the expression of these genes, all of which play an important role in cholesterol metabolism, will be examined in intestinal cells.

Conditions

Healthy Participants

Keywords

GPR146; Cholesin; Cholesterol metabolism; Gene expression; Postprandial study; Intestinal cholesterol absorption; Hepatic cholesterol synthesis; Plant sterols

Outcome Measures

Primary Outcomes (1)

• The postprandial changes in GPR146 gene expression in peripheral blood mononuclear cells (PBMCs) after three dietary conditions.

  The gene expression levels will be determined by messenger RNA (mRNA) quantification using the real-time reverse transcription polymerase chain reaction (RT-qPCR) method in PBMCs and reported as fold change (increase or decrease) relative to baseline.

  At baseline (fasting; before the meal) and at 360 minutes (6-hours) postprandial

Secondary Outcomes (2)

• The postprandial changes in C7orf50, HMGCR, and LDLR gene expressions in peripheral blood mononuclear cells (PBMCs) after three dietary conditions.

  At baseline (fasting; before the meal) and at 360 minutes (6-hours) postprandial

• The postprandial changes in GPR146 and LDLR protein expressions in peripheral blood mononuclear cells after three dietary conditions.

  At baseline (fasting; before the meal) and at 360 minutes (6-hours) postprandial

Other Outcomes (2)

• The changes in small intestinal mucosal cells gene expression profiles of GPR146, C7orf50, HMGCR, and LDLR genes after the three meals

  6-hours postprandial

• The postprandial response of serum triacylglycerol (TAG) and apolipoprotein B-48 (apoB-48) to the three meals

  At intervals of 7 time-points during the postprandial period (0-6 hours)

Study Arms (3)

Cholesterol-poor, plant sterol-poor shake

ACTIVE COMPARATOR

Participants will be given a mixed meal in the form of a cholesterol-poor, plant-sterol-poor shake.

Dietary Supplement: Cholesterol-poor, plant sterol-poor shake

Cholesterol-rich, plant sterol-poor shake

ACTIVE COMPARATOR

Participants will be given a mixed meal in the form of a cholesterol-rich, plant-sterol-poor shake.

Dietary Supplement: Cholesterol-rich, plant sterol-poor shake

Cholesterol-rich plant sterol-rich shake

EXPERIMENTAL

Participants will be given a mixed meal in the form of a cholesterol-rich, plant-sterol-rich shake.

Dietary Supplement: Cholesterol-rich, plant sterol-rich shake

Interventions

Cholesterol-poor, plant sterol-poor shake DIETARY_SUPPLEMENT

The first arm is the cholesterol-poor arm, where participants will be given a mixed meal in the form of a cholesterol-poor, plant-sterol-poor shake which provides the lowest cholesterol absorption rate.

Cholesterol-poor, plant sterol-poor shake

Cholesterol-rich, plant sterol-poor shake DIETARY_SUPPLEMENT

The second arm is the high-cholesterol arm, where participants will be given a mixed meal in the form of a cholesterol-rich, plant-sterol-poor shake, which provides the highest cholesterol absorption rate.

Cholesterol-rich, plant sterol-poor shake

Cholesterol-rich, plant sterol-rich shake DIETARY_SUPPLEMENT

The third arm is the moderate-cholesterol arm, where participants will be given a mixed meal in the form of a cholesterol-rich, plant-sterol-rich shake, which provides the moderate cholesterol absorption rate.

Cholesterol-rich plant sterol-rich shake

Eligibility Criteria

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

You may qualify if:

• Men and women, aged between 18-70 years
• BMI between 18.5-25.0 kg/m2
• Fasting serum total cholesterol (TC) \<8.0 mmol/L and fasting serum triacylglycerol (TAG) \<3 mmol/L
• Fasting plasma glucose (FBG) \<7 mmol/L
• Systolic blood pressure \<160 mmHg and diastolic blood pressure \<100 mmHg
• Stable body weight (weight gain or loss of \<3 kg in the past three months)
• Willingness to give up being a blood donor from 8 weeks before the start of the study, during the study, and for 4 weeks after completion of the study
• No difficult venipuncture as evidenced during the screening visit

You may not qualify if:

• Allergy or intolerance to any of the components of the study meal
• Familial hypercholesterolemia
• History of gastrointestinal surgery, including bariatric procedures such as sleeve gastrectomy, gastric bypass, gastric band, gastric balloon, or other major gastrointestinal surgeries that may affect digestion or absorption
• Current smokers
• Diabetic patients
• Pregnant and breastfeeding women
• Abuse of drugs
• More than 10 alcoholic consumptions per week for women and 14 for men
• Not willing to stop the use of products or dietary supplements known to interfere with the main outcomes as judged by the principal investigator for at least 1 week before the start of the study
• Use of medications to treat or affect blood pressure, lipid, or glucose metabolism
• Use of an investigational product within another biomedical intervention trial within the previous 1 month
• Severe medical conditions that might interfere with the study, such as: epilepsy, asthma, kidney failure or renal insufficiency, chronic obstructive pulmonary disease, inflammatory bowel diseases, autoinflammatory diseases, and rheumatoid arthritis
• Active cardiovascular disease, such as congestive heart failure, or a cardiovascular event, such as an acute myocardial infarction or a cerebrovascular accident

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Study Sites (1)

Maastricht University

Maastricht, Limburg, 6229 ER, Netherlands

Location

Central Study Contacts

Jogchum Plat, PhD

CONTACT

+31-43-3881309; j.plat@maastrichtuniversity.nl

Dena Nuwaylati, MD, MSc

CONTACT

+31-433881599; dena.nuwaylati@maastrichtuniversity.nl

Study Design

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

Study Record Dates

• First Submitted: August 19, 2025
• First Posted: August 26, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: October 1, 2025

Record last verified: 2025-08

Locations

NL (1)