Atorvastatin + Dietary Changes for High Cholesterol in Epilepsy

Overseen By Tanya J McDonald, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Johns Hopkins University

Must not be taking: Statins

Disqualifiers: ASCVD, Carnitine deficiency, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

22 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not be currently using statin medications to participate.

What data supports the effectiveness of the drug atorvastatin for high cholesterol in epilepsy?

Atorvastatin, a drug known for lowering cholesterol, also has neuroprotective effects and may help with seizure control in epilepsy, as shown in studies where it increased the seizure threshold in animal models. ^{1 2 3 4 5}

Is atorvastatin safe for people with epilepsy?

Atorvastatin, commonly known as Lipitor, is generally safe for humans and has been used to lower cholesterol. It also has neuroprotective effects and may help with conditions like stroke and brain injury, but there are some interactions with epilepsy medications that should be monitored. ^{2 4 5 6 7}

How is the drug atorvastatin unique for treating high cholesterol in epilepsy?

Atorvastatin is unique because, in addition to lowering cholesterol, it has shown potential neuroprotective and antiepileptic effects, which may help in managing seizures in epilepsy through nitric oxide pathways. ^{2 4 5 7 8}

What is the purpose of this trial?

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.

Research Team

Tanya J McDonald, MD, PhD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

Adults with epilepsy who have been on a Modified Atkins Diet for over a year and have high cholesterol as defined by specific guidelines. They must be at least 18 years old, have a BMI over 18.5, and their seizure medications should not have changed in the last month.

Inclusion Criteria

I have been following the Modified Atkins Diet for at least 12 months.

My BMI is over 18.5.

My seizure medication has not changed in over a month.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to either modify their Modified Atkins Diet or take atorvastatin for 12 weeks

12 weeks

Regular visits for monitoring and adherence checks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Atorvastatin
• Modification of dietary fat composition

Trial Overview The trial is testing whether changing dietary fat composition or taking Atorvastatin (a cholesterol-lowering medication) can reduce high cholesterol levels without affecting seizure control or diet adherence in adults using ketogenic diet therapies for epilepsy.

Participant Groups

Group I: Modified Atkins diet (MAD) Modification Experimental Treatment 1 Intervention

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.

Group II: Statin Active Control 1 Intervention

Participants will receive 10mg of atorvastatin daily for 12 weeks

Atorvastatin is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in United States as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia
• Prevention of cardiovascular disease

Approved in Canada as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia
• Prevention of cardiovascular disease

Approved in Japan as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in China as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in Switzerland as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

American Heart Association

Collaborator

Trials

352

Recruited

6,196,000+

References

1. United States pubmed.ncbi.nlm.nih.gov

Statins as an antiepileptogenic or disease-modifying treatment? A survey of what UK patients and significant others think about repurposing and trialing them for epilepsy. [2023]

2. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Statins and epilepsy: preclinical studies, clinical trials and statin-anticonvulsant drug interactions. [2019]

3. United Arab Emirates pubmed.ncbi.nlm.nih.gov

The number of antiseizure medications taken and not the lipid profile was associated with seizure control in adult patients with epilepsy. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Differential effects of atorvastatin treatment and withdrawal on pentylenetetrazol-induced seizures. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Anticonvulsive effect of atorvastatin on pentylenetetrazole-induced seizures in mice: the role of nitric oxide pathway. [2018]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Statin use for the prevention of seizure and epilepsy in the patients at risk: A systematic review and meta-analysis of cohort studies. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Effects of lamotrigine and phenytoin on the pharmacokinetics of atorvastatin in healthy volunteers. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Subtle improvement of seizure susceptibility by atorvastatin treatment during epileptogenesis. [2020]