GPR146 and Cholesterol Metabolism

NCT ID: NCT07142317

Last Updated: 2025-10-01

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-31
• Study Completion Date: 2026-12-31

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

Study Design

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

Study Groups

Cholesterol-poor, plant sterol-poor shake

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

Group Type: ACTIVE_COMPARATOR

Cholesterol-poor, plant sterol-poor shake

Intervention Type: 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-rich, plant sterol-poor shake

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

Group Type: ACTIVE_COMPARATOR

Cholesterol-rich, plant sterol-poor shake

Intervention Type: 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-rich shake

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

Group Type: EXPERIMENTAL

Cholesterol-rich, plant sterol-rich shake

Intervention Type: 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.

Interventions

Cholesterol-poor, plant sterol-poor shake

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.

Intervention Type: DIETARY_SUPPLEMENT

Cholesterol-rich, plant sterol-poor shake

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.

Intervention Type: DIETARY_SUPPLEMENT

Cholesterol-rich, plant sterol-rich shake

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.

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Maastricht University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Maastricht University

Maastricht, Limburg, Netherlands

Countries

Netherlands

Central Contacts

Jogchum Plat, PhD

Role: CONTACT

j.plat@maastrichtuniversity.nl

+31-43-3881309

Dena Nuwaylati, MD, MSc

Role: CONTACT

dena.nuwaylati@maastrichtuniversity.nl

+31-433881599

Facility Contacts

Nele Steenackers, PhD

Role: primary

nele.steenackers@maastrichtuniversity.nl

+31-433881539

Other Identifiers

METC 25-027

Identifier Type: -

Identifier Source: org_study_id