Cardiovascular Risk Reduction in Epilepsy

Cardiovascular Risk in Epilepsy: Pilot Feasibility and Efficacy Study of Neurologist-Initiated Treatment of Hypertension and Hyperlipidemia in an Underserved Minority Population in Los Angeles

Epilepsy is a disabling and lethal neurological disease which affect 3.47 million Americans. Significant health care disparities exist in people with epilepsy (PWE). Hypertension and hyperlipidemia are highly prevalent and often go undertreated, and cardiovascular (CV) mortality is higher in people with epilepsy (PWE) than the general population. Preliminary data from our group shows that PWE have higher ACC-ASCVD risk scores than an age matched NHANES cohort without epilepsy. Preliminary data also demonstrate mortality rates in PWE due to hypertension, stroke, and diabetes are rising in the US, counter to the US general population.

This proposal seeks to test the feasibility, acceptability, and preliminary efficacy of a new care model for the underserved PWE in a public health setting. In this new model, neurologists guided by standardized treatment algorithms (ACC-ASCVD estimator+) propose and initiate pharmacological interventions for hypertension and hyperlipidemia.

Study Overview

• Status: Withdrawn
• Conditions: Epilepsy; Hypertension; Hyperlipidemia (E.G., Hypercholesterolemia)
• Intervention / Treatment: Drug: Neurologist Initiated Treatment; Other: Placebo

Detailed Description

Epilepsy is a disabling and lethal neurological disease which affect 3.47 million Americans. Significant health care disparities exist in people with epilepsy (PWE). PWE are more likely to be Hispanic, Black, developmentally disabled and unemployed. Hypertension and hyperlipidemia are highly prevalent and often go undertreated, and cardiovascular (CV) mortality is higher in people with epilepsy (PWE) than the general population. Preliminary data from our group shows that PWE have higher ACC-ASCVD risk scores than an age matched NHANES cohort without epilepsy. Preliminary data also demonstrate mortality rates in PWE due to hypertension, stroke, and diabetes are rising in the US, counter to the US general population.

PWE on Medicaid, Medi-Cal and without insurance are more likely to experience delays to treatment and follow aberrant care pathways. Unexpected seizures and status epilepticus often result in transport to community and public health hospitals, where they are referred to neurology clinics, a process which may bypass primary care. As a result, PWE may have as their primary point of contact neurologists who traditionally do no monitor or treat hypertension or hyperlipidemia. This leads to gaps in care and missed opportunities to reduce CV risk.

This proposal seeks to test the feasibility, acceptability, and preliminary efficacy of a new care model for the underserved PWE in a public health setting. In this new model, neurologists guided by standardized treatment algorithms (ACC-ASCVD estimator+) propose and initiate pharmacological interventions for hypertension and hyperlipidemia.

We propose enrolling 150 subjects ages 40-79 with untreated or incompletely treated hypertension and/or hyperlipidemia. Subjects will be randomized 2:1 to Neurologist-initiated treatment (Model 1) versus usual care (Model 2). Subjects will be evaluated for blood pressure, blood chemistries, lipids, and HgA1C at baseline, one and three months. At 3-months, subjects randomized to usual care (Model 2) will be offered treatment if not yet initiated by primary care. If successful, results of this pilot study will provide needed feasibility and preliminary efficacy data for a large multicenter randomized trial of Neurologist initiated treatment of cardiovascular risk in the underserved with epilepsy

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Epilepsy defined as G40.0-G40.9 in the electronic medical record, or seizure disorder prescribed at least one antiseizure medication
• Age 40-79 (age range defined by ACC-ASCVD risk estimator+)
• Untreated HTN defined as at least two sitting BPs > 130/80 in the last year prior to enrollment or on enrollment
• Hyperlipidemia defined as LDL > 70 mg/dl with 10-year ACC-ASCVD score > 7.5% or total LDL > 190, or ASCVD recommendation to initiate lipid lowering agent
• Intellectual Disability, developmental disorder or autism recorded in the electronic medical record (ICD-10 codes F70-F79, F84)

Exclusion Criteria:

• Stroke or cerebral hemorrhage < 1 year
• Documented poor compliance with treatment
• If intellectually disabled, if there is no caregiver to support or initiate therapy
• Pregnancy or person actively trying to become pregnant
• Blood Pressure > 180/110
• Known secondary cause of hypertension that causes concern regarding safety of the protocol.
• Arm circumference too large or small to allow accurate blood pressure measurement with available devices
• Diabetes mellitus,
• Glomerulonephritis treated with or likely to be treated with immunosuppressive therapy
• eGFR < 20 ml/min /1.73m2 or end-stage renal disease (ESRD)
• Cardiovascular event, procedure or hospitalization for unstable angina within last 3 months
• Symptomatic heart failure within the past 6 months
• A medical condition likely to limit survival to less than 3 years or a malignancy other than non-melanoma skin cancer within the last 2 years
• Any factors judged by the clinic team to be likely to limit adherence to interventions.
• Failure to obtain informed consent from participant
• Any organ transplant

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Model 1-Neurologist Initiation of Treatment for Hypertension or Hyperlipidemia; Neurologist Initiation of antihypertensive or treatment for hyperlipidemia	Drug: Neurologist Initiated Treatment; Neurologist Initiated Treatment for Hypertension or Hyperlipidemia; Other Names: antihypertensive agent or Hyperlipidemia agent
Placebo Comparator: Model 2-Usual Care; Usual care	Other: Placebo; Usual care; Other Names: Usual Care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ACC-ASCVD score from baseline	Percent change in ACC-ASCVD score (ACC-ASCVD) compared with baseline	3-months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic blood pressure	change in blood pressure (mmHg)	3 months
Total Cholesterol	change in total cholesterol (mg/dl) from baseline	3 months
LDL-low density lipoprotein	change in low density lipoprotein (mg/dl) from baseline	3 months
Compliance	Percent of enrolled subjects who complete visit three	3 months
Acceptability Rate	Rate: Number of medication proposals accepted by primary care physicians/number of medication proposals submitted to primary care physicians	3 months

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: Olive View-UCLA Education & Research Institute
• Investigators: Principal Investigator: Christopher M DeGiorgio, MD, University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: January 11, 2023
• First Submitted That Met QC Criteria: January 19, 2023
• First Posted (Actual): January 30, 2023

Study Record Updates

• Last Update Posted (Actual): July 25, 2024
• Last Update Submitted That Met QC Criteria: July 24, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Epilepsy; Hypertension; Hyperlipidemia; Underserved
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Lipid Metabolism Disorders; Dyslipidemias; Epilepsy; Hypertension; Hypercholesterolemia; Hyperlipidemias; Hyperlipoproteinemias; Antihypertensive Agents
• Other Study ID Numbers: CMD01

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No