Antiepileptic Drugs and Vascular Risk Markers

December 14, 2017 updated by: Thomas Jefferson University

The Effects of Antiepileptic Drugs on Serum Lipids and Inflammation in Patients With Subarachnoid Hemorrhage

The purpose of this study is to determine if certain seizure medications raise levels of cholesterol and other blood components which could increase the risk of heart attacks and strokes.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

There is some evidence that certain seizure medicines may raise levels of cholesterol and other blood components which could increase the risk of heart attacks and strokes, however, more research is needed. Individuals with acute subarachnoid hemorrhage traditionally are treated with seizure medicines, but it is not clear which one is best, or if any such medication is necessary at all.

This study is intended to find out if certain seizure medications raise levels of cholesterol and other blood components which could lead to an increased risk of heart attacks and strokes.

In this study, 200 people with acute subarachnoid hemorrhage will be randomized to treatment with one of three different seizure medicines-phenytoin, valproate, or levetiracetam-or to receive no seizure medication at all. In each participant, cholesterol and other blood markers that relate to heart attack and stroke risk will be measured shortly after hospital admission and again 8 weeks later. At the 8-week point most participants will have their seizure medication discontinued, and the same blood tests will be repeated.

Information from this study could lead to changes in how seizure medications are prescribed both in the subarachnoid hemorrhage population and in other people who are prone to seizures.

Study Type

Interventional

Enrollment (Actual)

52

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Acute subarachnoid hemorrhage, Hunt-Hess Grades I-IV
  • Within 48 hours of admission

Exclusion Criteria:

  • Grade V subarachnoid hemorrhage
  • Being treated with a lipid-lowering agent
  • Contraindication to phenytoin, valproate, or levetiracetam (e.g. history of allergy to one of these agents)
  • Contraindication to receiving no antiepileptic drug treatment (e.g. history of pre-existing epilepsy, seizure activity on admission EEG)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 1
Participants randomized to Group 1 will receive phenytoin (PHT) at 5 mg/kg/day in 2 divided doses.
Drug: phenytoin
Phenytoin is a anti-seizure medication. Participants will receive phenytoin (PHT) at 5 mg/kg/day in 2 divided doses.
Other Names:
  • Dilantin, Cerebyx (a phenytoin pro-drug)
Active Comparator: 2
Participants randomized to Group 2 will receive valproate (VPA) at 15 mg/kg/day in 3 divided doses or in a once-daily extended release formulation.
Drug: valproate
Valproate is an anti-seizure medication. Participants will receive valproate (VPA) at 15 mg/kg/day in 3 divided doses.
Other Names:
  • Depakote, Depacon
Active Comparator: 3
Participants randomized to Group 3 will receive levetiracetam (LEV) 1000-1500 mg/day in 2 divided doses.
Drug: levetiracetam
Levetiracetam is an anti-seizure medication. Participants will receive levetiracetam (LEV) 1000-1500 mg/day in 2 divided doses.
Other Names:
  • Keppra
No Intervention: 4
Participants randomized to Group 4 will receive no drug intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in Serum Cholesterol, Non-HDL Cholesterol, HDL Cholesterol, Lipoprotein(a), and C-reactive Protein From Baseline to Second Draw and Third Draw in Each of the 4 Study Arms
Time Frame: 8 weeks, 16 weeks
8 weeks, 16 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Incidence of Acute Seizures, Incidence of Late Seizures, Overall Neurologic Function (as Measured by Modified Rankin Scale Scores)
Time Frame: 8 weeks, 16 weeks
8 weeks, 16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Thomas Jefferson University

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

  • Principal Investigator: Scott Mintzer, MD, Assistant Professor of Neurology, Jefferson Comprehensive Epilepsy Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2009

Primary Completion (Actual)

June 1, 2012

Study Completion (Actual)

June 1, 2012

Study Registration Dates

First Submitted

October 16, 2008

First Submitted That Met QC Criteria

October 16, 2008

First Posted (Estimate)

October 17, 2008

Study Record Updates

Last Update Posted (Actual)

December 18, 2017

Last Update Submitted That Met QC Criteria

December 14, 2017

Last Verified

December 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • K23NS058669 (U.S. NIH Grant/Contract)
  • 1K23NS058669 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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