Hypercholesterolemia and HyperlipidemiaNCT06894004
Mechanism of Ketogenic Diet-Induced Hypercholesterolemia
A study testing Ketogenic Diet in people with Hypercholesterolemia and Hyperlipidemia, run by Washington University School of Medicine at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 39 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypercholesterolemia and Hyperlipidemia
- What is being tested?
- Ketogenic Diet
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Feb 2025to 30 Nov 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 39 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- age ≥ 18 and < 40 years
- BMI ≥ 18.5 and < 25.0 kg/m2
- baseline serum LDL-c < 150 mg/dL (< 3.9 mmol/L)
- baseline serum TG < 100 mg/dL (< 1.1 mmol/L)
- HbA1c ≤ 5.6%.
Who cannot join
- personal or family history of familial hypercholesterolemia
- current use of lipid-lowering drugs
- currently on a ketogenic diet and unwilling to change diet
- current tobacco use
- hypertension
- prediabetes or diabetes
Show all 11Show fewer
- elevated Lp(a) > 6.5% of ApoB-containing lipoproteins at baseline
- oral contraceptive use
- contraindication to heparin
- known atherosclerotic cardiovascular disease
- unwilling to abstain from alcohol
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Nikki Plassmeyer, M.A., R.D.N., L.D., (314) 362-0590, nikkip@wustl.edu
Max C Petersen, M.D., Ph.D., 314-362-8450, max.p@wustl.edu
About this study
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.
Read the 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
- Being tested
- Ketogenic Diet, Control Diet
- Keywords
- LDL-cholesterol, cholesterol, ketogenic diet, lipoprotein kinetics
- Medical subject headings
- Hypercholesterolemia, Hyperlipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketogenic DietBehavioural
Participants will consume an isocaloric ketogenic diet for 4 weeks with all food provided as packed-out meals.
Control DietBehavioural
Participants will consume an isocaloric control diet for 4 weeks with all food provided as packed-out meals.
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Arm A will complete the Ketogenic Diet intervention first, followed by the Control Diet intervention after a 4-week washout period. Receives: Behavioral: Ketogenic Diet; Behavioral: Control Diet |
| B | Experimental | Arm B will complete the Control Diet intervention first, followed by the Ketogenic Diet intervention after a 4-week washout period. Receives: Behavioral: Ketogenic Diet; Behavioral: Control Diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
VLDL-ApoB100 production rate
Determined by using plasma and VLDL-ApoB100 leucine isotopic enrichment and compartmental modeling
Measured: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Secondary outcomes (18)
VLDL-ApoB100 fractional catabolic rate
Determined by using plasma and VLDL-ApoB100 leucine isotopic enrichment and compartmental modeling
Measured: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
IDL-ApoB100 production rate
Determined by using plasma and IDL-ApoB100 leucine isotopic enrichment and compartmental modeling
Measured: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
IDL-ApoB100 fractional catabolic rate
Determined by using plasma and IDL-ApoB100 leucine isotopic enrichment and compartmental modeling
Measured: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
LDL-ApoB100 production rate
Determined by using plasma and LDL-ApoB100 leucine isotopic enrichment and compartmental modeling
Measured: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
LDL-ApoB100 fractional catabolic rate
Determined by using plasma and LDL-ApoB100 leucine isotopic enrichment and compartmental modeling
Measured: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
VLDL-triglyceride production rate
Determined by using plasma and VLDL glycerol isotopic enrichment and compartmental modeling
Measured: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
VLDL-triglyceride fractional catabolic rate
Determined by using plasma and VLDL glycerol isotopic enrichment and compartmental modeling
Measured: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Plasma lipoprotein lipase activity
Determined by assaying lipoprotein lipase activity in post-heparin plasma
Measured: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Plasma lipoprotein profile
Determined by standard clinical chemistry methods and by advanced lipoprotein profiling
Measured: At baseline, immediately after the screening ketogenic diet, immediately after the 4-week ketogenic diet intervention period, and immediately after the 4-week control diet intervention period.
Whole-body lipolytic rate
Determined by using plasma palmitate isotopic enrichment
Measured: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Relative contribution of systemic fatty acids to VLDL-triglyceride
Determined by using plasma and VLDL-triglyceride palmitate isotopic enrichment and compartmental modeling
Measured: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Cholesterol synthetic rate
Determined by using mass isotopomer distribution analysis of deuterium enrichment in plasma cholesterol after labeling the total body water pool with deuterium oxide
Measured: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Fat mass
Determined by using dual-energy X-ray absorptiometry
Measured: Immediately after the screening ketogenic diet
Fat-free mass
Determined by using dual-energy X-ray absorptiometry
Measured: Immediately after the screening ketogenic diet
Insulin sensitivity
Determined by measuring fasting plasma glucose, insulin, and C-peptide
Measured: Immediately after the screening ketogenic diet
Thyroid function
Determined by measuring TSH, free T4, and free T3
Measured: Immediately after the screening ketogenic diet
Adipokines
Determined by measuring plasma leptin and adiponectin
Measured: Immediately after the screening ketogenic diet
Cholesterol absorption markers
Determined by measuring serum campesterol, sitosterol, and cholestanol
Measured: Immediately after the screening ketogenic diet
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2025
- Study start24 Feb 2025
- Primary completion30 Nov 2030 (estimated)
- Study completion30 Nov 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hypercholesterolemia and HyperlipidemiaStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Max C Petersen, M.D., Ph.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06894004
- Sponsor's protocol ID
- 202409091
- Status last verified
- Mar 2026
- First submitted
- 10 Mar 2025
- Last updated
- 23 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All raw data used to generate descriptive statistics presented in manuscripts incorporating results generated from this study will be included as supplemental data files as and when required. Fully de-identified raw data, including all outcome measures and tracer enrichments from kinetic studies will be available in .csv format, which can be manipulated by many free and commercial software packages. Individual-level data will be shared as allowed by informed consent agreements approved by the Institutional Review Board (IRB).
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanism of Ketogenic Diet-Induced Hypercholesterolemia
- ClinicalTrials.gov ID
- NCT06894004
- Acronym / sponsor ID
- 202409091
- Conditions
- Hypercholesterolemia and Hyperlipidemia
- Keywords
- LDL-cholesterol, cholesterol, ketogenic diet, lipoprotein kinetics
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 24 Feb 2025 (actual)
- Primary completion
- 30 Nov 2030 (estimated)
- Study completion
- 30 Nov 2030 (estimated)
- First posted
- 25 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Behavioral: Ketogenic Diet, Behavioral: Control DietArm A will complete the Ketogenic Diet intervention first, followed by the Control Diet intervention after a 4-week washout period. |
| B | Experimental | Behavioral: Ketogenic Diet, Behavioral: Control DietArm B will complete the Control Diet intervention first, followed by the Ketogenic Diet intervention after a 4-week washout period. |
Who may qualify
- Ages
- 18 to 39 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- age ≥ 18 and < 40 years
- BMI ≥ 18.5 and < 25.0 kg/m2
- baseline serum LDL-c < 150 mg/dL (< 3.9 mmol/L)
- baseline serum TG < 100 mg/dL (< 1.1 mmol/L)
- HbA1c ≤ 5.6%.
Key exclusion criteria (11 listed)
- personal or family history of familial hypercholesterolemia
- current use of lipid-lowering drugs
- currently on a ketogenic diet and unwilling to change diet
- current tobacco use
- hypertension
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketogenic DietParticipants will consume an isocaloric ketogenic diet for 4 weeks with all food provided as packed-out meals. | Behavioural | A, B |
| Control DietParticipants will consume an isocaloric control diet for 4 weeks with all food provided as packed-out meals. | Behavioural | A, B |
Primary outcome
VLDL-ApoB100 production rate
Time frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Determined by using plasma and VLDL-ApoB100 leucine isotopic enrichment and compartmental modeling
18 secondary outcomes
VLDL-ApoB100 fractional catabolic rate
Time frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
IDL-ApoB100 production rate
Time frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
IDL-ApoB100 fractional catabolic rate
Time frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
LDL-ApoB100 production rate
Time frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
LDL-ApoB100 fractional catabolic rate
Time frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
VLDL-triglyceride production rate
Time frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
VLDL-triglyceride fractional catabolic rate
Time frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Plasma lipoprotein lipase activity
Time frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Plasma lipoprotein profile
Time frame: At baseline, immediately after the screening ketogenic diet, immediately after the 4-week ketogenic diet intervention period, and immediately after the 4-week control diet intervention period.
Whole-body lipolytic rate
Time frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Relative contribution of systemic fatty acids to VLDL-triglyceride
Time frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Cholesterol synthetic rate
Time frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Fat mass
Time frame: Immediately after the screening ketogenic diet
Fat-free mass
Time frame: Immediately after the screening ketogenic diet
Insulin sensitivity
Time frame: Immediately after the screening ketogenic diet
Thyroid function
Time frame: Immediately after the screening ketogenic diet
Adipokines
Time frame: Immediately after the screening ketogenic diet
Cholesterol absorption markers
Time frame: Immediately after the screening ketogenic diet
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2026.
- Individual participant dataSharing planned: Yes. All raw data used to generate descriptive statistics presented in manuscripts incorporating results generated from this study will be included as supplemental data files as and when required. Fully de-identified raw data, including all outcome measures and tracer enrichments from kinetic studies will be available in .csv format, which can be manipulated by many free and commercial software packages. Individual-level data will be shared as allowed by informed consent agreements approved by the Institutional Review Board (IRB).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Max C Petersen, M.D., Ph.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ketogenic Diet in people with Hypercholesterolemia and Hyperlipidemia, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Frannie Wilkinson, M.A. ((314) 362-0590, francesw@wustl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
VLDL-ApoB100 production rate (time frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2026.