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

Phase 1

• Conditions: Epilepsy; Dyslipidemia
• Interventions: Drug: Atorvastatin 10mg; Other: Modification of dietary fat composition

• Registration Number: NCT06369571
• Lead Sponsor: Johns Hopkins University

Brief Summary

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.

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 Timeline

• Study First Submitted: 2024-04-12
• Study First Submitted QC: 2024-04-12
• Study First Posted: 2024-04-17
• Status Verified: 2024-10
• Study Start: 2024-10-04
• Last Update Submitted: 2024-10-25
• Last Update Posted: 2024-10-29
• Primary Completion: 2027-01
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 22

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Statin	Atorvastatin 10mg	Participants will receive 10mg of atorvastatin daily for 12 weeks
Modified Atkins diet (MAD) Modification	Modification of dietary fat composition	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.

Primary Outcome Measures

Name	Time	Method
Statin Adherence	12 weeks	Statin adherence will be determined based on pills returned at study completion, with participants labeled adherent if 80% or more of pills were consumed.
Diet adherence as assessed by 3 day food records	12 weeks	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.
Change in weekly seizure frequency	12 weeks	12-week difference in weekly seizure frequency from baseline
LDL Change	12 weeks	12-week % LDL change from baseline within arms and between arms
Seizure severity questionnaire score	12 weeks	12-week difference in seizure severity questionnaire (SSQ) score (score 1-7, with higher score indicating more severe seizures)

Secondary Outcome Measures

Name	Time	Method
Blood ketone change	12 weeks	12-week difference in serum beta-hydroxybutyrate level from baseline
Frequency of adverse events	12 weeks	Frequency of adverse events

Trial Locations

Locations (1)

Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States