Mechanism of Ketogenic Diet-Induced Hypercholesterolemia

NCT ID: NCT06894004

Last Updated: 2025-03-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-24
• Study Completion Date: 2030-11-30

Brief Summary

Very-low carbohydrate ketogenic diets can dramatically increase blood cholesterol levels, particularly in normal-weight people, for reasons that are not well understood. This study will enroll normal-weight adults, will identify "responders" who develop high cholesterol on a ketogenic diet, and will measure rates of production and removal of certain types of cholesterol-carrying particles called lipoproteins in responders. The results will clarify the mechanism by which a ketogenic diet can cause high cholesterol in certain susceptible people.

Detailed Description

This study will evaluate the mechanism of ketogenic diet-induced hypercholesterolemia in susceptible normal-weight adults. The first stage of screening will identify eligible young adults who are normal-weight and at low cardiovascular risk. The second stage of screening will identify "responders" who demonstrate susceptibility to ketogenic diet-induced hypercholesterolemia by displaying an increase in LDL-cholesterol concentration after a 3-week screening ketogenic diet. Responders will be eligible to complete a randomized crossover clinical study at Washington University School of Medicine in St. Louis, MO. The randomized crossover study will involve isotope tracer studies of lipoprotein and cholesterol kinetics after two separate 4-week dietary interventions [ketogenic diet and control diet], conducted in random order with a 4-week washout period between interventions. All food will be provided to the participants as packed-out meals. Certain outcomes will use data from the screening process, comparing screen successes and screen failures to evaluate factors that could influence susceptibility to ketogenic diet-induced hypercholesterolemia.

Conditions

Hypercholesterolemia and Hyperlipidemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

A

Arm A will complete the Ketogenic Diet intervention first, followed by the Control Diet intervention after a 4-week washout period.

Group Type: EXPERIMENTAL

Ketogenic Diet

Intervention Type: BEHAVIORAL

Participants will consume an isocaloric ketogenic diet for 4 weeks with all food provided as packed-out meals.

Control Diet

Intervention Type: BEHAVIORAL

Participants will consume an isocaloric control diet for 4 weeks with all food provided as packed-out meals.

B

Arm B will complete the Control Diet intervention first, followed by the Ketogenic Diet intervention after a 4-week washout period.

Group Type: EXPERIMENTAL

Ketogenic Diet

Intervention Type: BEHAVIORAL

Participants will consume an isocaloric ketogenic diet for 4 weeks with all food provided as packed-out meals.

Control Diet

Intervention Type: BEHAVIORAL

Participants will consume an isocaloric control diet for 4 weeks with all food provided as packed-out meals.

Interventions

Ketogenic Diet

Participants will consume an isocaloric ketogenic diet for 4 weeks with all food provided as packed-out meals.

Intervention Type: BEHAVIORAL

Control Diet

Participants will consume an isocaloric control diet for 4 weeks with all food provided as packed-out meals.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

1. age ≥ 18 and < 40 years

2. BMI ≥ 18.5 and < 25.0 kg/m2

3. baseline serum LDL-c < 150 mg/dL (< 3.9 mmol/L)

4. baseline serum TG < 100 mg/dL (< 1.1 mmol/L)

5. HbA1c ≤ 5.6%.

Exclusion Criteria

1. personal or family history of familial hypercholesterolemia

2. current use of lipid-lowering drugs

3. currently on a ketogenic diet and unwilling to change diet

4. current tobacco use

5. hypertension

6. prediabetes or diabetes

7. elevated Lp(a) > 6.5% of ApoB-containing lipoproteins at baseline

8. oral contraceptive use

9. contraindication to heparin

10. known atherosclerotic cardiovascular disease

11. unwilling to abstain from alcohol

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 39 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Max C Petersen, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Nikki Plassmeyer, M.A., R.D.N., L.D.

Role: CONTACT

nikkip@wustl.edu

(314) 362-0590

Max C Petersen, M.D., Ph.D.

Role: CONTACT

max.p@wustl.edu

314-362-8450

Facility Contacts

Nikki Plassmeyer, M.A., R.D.N., L.D.

Role: primary

nikkip@wustl.edu

(314) 362-0590

Max C Petersen, M.D., Ph.D.

Role: backup

max.p@wustl.edu

314-362-8450

Other Identifiers

202409091

Identifier Type: -

Identifier Source: org_study_id