Improving Cardiovascular Health Risks in Adults With Epilepsy on a Modified Atkins Diet

Ketogenic diet therapies (KDTs) emphasize high fat and very low carbohydrate intake and help to control seizures in adults who fail to respond to medications. However, KDT use can lead to increased cholesterol levels in some adults with epilepsy (AWE). Treatments that can reverse elevations in cholesterol observed with long-term KDT use without compromising diet adherence and seizure control are needed. The proposed study will explore the feasibility and safety of diet modification and statin use to lower cholesterol in this population. Study findings will help guide doctors utilizing KDTs in adults with epilepsy on how to approach managing elevations in cholesterol.

Study Overview

• Status: Enrolling by invitation
• Conditions: Epilepsy; Dyslipidemia
• Intervention / Treatment: Drug: Atorvastatin 10mg; Other: Modification of dietary fat composition

Detailed Description

The scientific premise of this proposal is that established or long-term (≥ 12 months) Modified Atkins diet (MAD) use in AWE influences atherosclerotic cardiovascular disease (ASCVD) risk and can be modified to reduce dyslipidemia when observed. Hence, the overarching goals of this proposal are to explore the safety and feasibility of dyslipidemia management strategies to reduce ASCVD risk in AWE on MAD without increasing seizure risk. This study will collect data before and after randomly assigned interventions to reduce LDL in AWE on long-term MAD recruited from patients receiving clinical care in the Johns Hopkins Adult Epilepsy Diet Center.

AWE with dyslipidemia on long-term MAD will be randomized 1:1 to either MAD modification (10% reduction of dietary energy from saturated fat, replaced with poly-unsaturated fat ) or moderate-intensity statin use (atorvastatin 10mg) for 12 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 22
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Modified Atkins Diet use ≥ 12 months
2. Dyslipidemia based on American College of Cardiology/American Heart Association guidelines (i.e., LDL ≥190 mg/dL, 10-year ASCVD risk ≥5% with risk enhancers, etc.)
3. 18 years of age or older
4. Body mass index (BMI) > 18.5
5. Stable anti-seizure medication regimen for > 1 month.

Exclusion Criteria:

1. < 18 years of age
2. Body mass index (BMI) < 18.5
3. Changes in anti-seizure medication regimen < 1 month prior to participation
4. Known ASCVD (history of acute coronary syndrome, myocardial infarction, angina, stroke, transient ischemic attack, or peripheral artery disease)
5. Current statin medication use
6. Prior serious adverse response to atorvastatin or other statin medications
7. Uncorrected carnitine deficiency
8. Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Statin; Participants will receive 10mg of atorvastatin daily for 12 weeks	Drug: Atorvastatin 10mg; Atorvastatin 10mg daily by mouth; Other Names: Lipitor
Experimental: Modified Atkins diet (MAD) Modification; Participants will be instructed on how to change their modified Atkins diet for 12 weeks. They will replace 10% of daily dietary energy from saturated fat with poly-unsaturated fat.	Other: Modification of dietary fat composition; Replace 10% of saturated fat intake with polyunsaturated fat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diet adherence as assessed by 3 day food records	Diet adherence will be based on the ability to achieve 10% reduction in dietary energy from saturated fat assessed from 3-day food records, the gold standard for diet intake assessments.	12 weeks
Statin Adherence	Statin adherence will be determined based on pills returned at study completion, with participants labeled adherent if 80% or more of pills were consumed.	12 weeks
LDL Change	12-week % LDL change from baseline within arms and between arms	12 weeks
Change in weekly seizure frequency	12-week difference in weekly seizure frequency from baseline	12 weeks
Seizure severity questionnaire score	12-week difference in seizure severity questionnaire (SSQ) score (score 1-7, with higher score indicating more severe seizures)	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of adverse events	Frequency of adverse events	12 weeks
Blood ketone change	12-week difference in serum beta-hydroxybutyrate level from baseline	12 weeks

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: American Heart Association
• Investigators: Principal Investigator: Tanya J McDonald, MD, PhD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: April 12, 2024
• First Submitted That Met QC Criteria: April 12, 2024
• First Posted (Actual): April 17, 2024

Study Record Updates

• Last Update Posted (Estimated): October 9, 2025
• Last Update Submitted That Met QC Criteria: October 7, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Cholesterol; Ketogenic Diet; Modified Atkins Diet
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Lipid Metabolism Disorders; Nutritional and Metabolic Diseases; Epilepsy; Dyslipidemias; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fatty Acids; Lipids; Azoles; Pyrroles; Heptanoic Acids; Atorvastatin
• Other Study ID Numbers: IRB00439268

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes