Exercise for Brain Regeneration in Epilepsy

Regenerating the Adult Human Brain Through Exercise

Nearly 100 million Americans are affected by neurological disorders with an overall cost above $765 billion for the more prevalent conditions. Given this significant burden, effective treatments to prevent dementia and new disease modifying therapies are urgently needed.

Regeneration of lost neurons with new ones (i.e., neurogenesis) is compromised at early stages of dementia and in part correlates with cognitive impairment in Alzheimer's disease. Boosting the neurogenesis delays the cognitive impairment in animal models of dementia and has been proven beneficial in improving the memory in rodent studies.

Aerobic exercise is the most potent known stimulator of neurogenesis in animal models. A crucial next step is to translate endogenous regenerative strategies to people. The purpose of this study is to demonstrate the feasibility and investigate the effects of an exercise program on neurogenesis and cognitive improvement in epilepsy patients.

Study Overview

• Status: Recruiting
• Conditions: Temporal Lobe Epilepsy
• Intervention / Treatment: Other: High-Impact Aerobic Exercise; Other: Low-Impact Aerobic Exercise

Detailed Description

Neurogenesis studies in healthy and dementia patients have only been performed on postmortem tissue, which prevents investigation of treatment outcomes. Patients with mesial temporal lobe epilepsy (MTLE) typically do not respond to medications and uniquely among related dementia disorders undergo corrective surgical treatment, providing a unique opportunity to study the value of regenerative interventions on hippocampal electrophysiology and neurogenesis. Using this unique approach, this study will investigate the neurogenesis and cognitive improvement in epilepsy patients.

Ten people with MTLE who are recommended for surgical treatment as part of their standard care will be enrolled and randomly assigned to High Impact (n=5) and Low Impact (n=5) exercise groups. The duration of exercise programs will be 12 weeks and study arms will undergo the same protocol except for the target heart rate which will be higher in the High-Impact group. Exercise will be performed at home using a recliner bike under the supervision of caregiver and study personnel. Participants will undergo cognitive, exercise and clinical assessment at baseline and after completing the three-month exercise therapy; then surgically resected tissue will be analyzed for regeneration and epileptiform activity. The investigators will assess whether exercise would yield clinical benefits in terms of seizure frequency/intensity or cognitive ability, and whether the ability of the adult human brain to self-repair can be enhanced. It is hypothesized that the proposed exercise regimen is feasible and will improve the neurogenesis levels and cognition.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jonathan J Russin, MD; Phone Number: 800-872-2273; Email: Jonathan.Russin@med.usc.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • University of Southern California Department of Neurosurgery
      • Contact: Jonathan J Russin, MD; Phone Number: 323-226-2271

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age of 18 years or older
• Medically resistant mesial temporal lobe epilepsy
• Candidacy for standard or selective temporal lobectomy

Exclusion Criteria:

• Age of older than 65 years
• Pregnancy
• Physical disabilities or medical conditions preventing from participation in exercise program
• Inability to receive exercise equipment at home
• Cognitive/developmental disabilities restricting the participation in exercise program

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-impact Exercise	Other: High-Impact Aerobic Exercise; Participants will be submitted to a 12-week high-impact aerobic exercise program using a recliner bike with three sessions per week. The exercise protocol takes 45 minutes per session and consists of five minutes of warm-up, 30 minutes of cycling with progressive increase in intensity until the target heart rate (80% of maximum) is reached, followed by 10 minutes of cool down.
Active Comparator: Low-impact Exercise	Other: Low-Impact Aerobic Exercise; Participants will be submitted to a 12-week low-impact aerobic exercise program using a recliner bike with three sessions per week. The exercise protocol takes 45 minutes per session and consists of five minutes of warm-up, 30 minutes of cycling with progressive increase in intensity until the target heart rate (40% of maximum) is reached, followed by 10 minutes of cool down.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adherence to exercise and assessments	Number of completed exercise and assessment sessions	Through study completion, an average of 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurogenesis	Number of new neurons per mm3 in surgically resected tissue after cell culture	13 weeks after first exercise session
Rey Auditory Verbal Learning Test (RAVLT) - Trial V	The Rey Auditory Verbal Learning Test (RAVLT) is a validated test evaluating verbal learning and memory. In this test, lists of words are read to the participants in consecutive trials. Trial V is the 5th attempt at recalling the first list of words.	Baseline and 12 weeks after first exercise session
Rey Auditory Verbal Learning Test (RAVLT) - Summary score	The Rey Auditory Verbal Learning Test (RAVLT) is a validated test evaluating verbal learning and memory. In this test, lists of words are read to the participants in consecutive trials. Summary score is the sum of number of words learned over five learning trials.	Baseline and 12 weeks after first exercise session
WAIS-IV - Matrix Reasoning	Wechsler Adult Intelligence Scale Fourth Edition (WAIS-IV) is a validated test of cognitive ability and intelligence. Matrix reasoning is among the tasks included in WAIS-IV which is used to assess non-verbal abstract problem solving and inductive reasoning.	Baseline and 12 weeks after first exercise session
Rey Complex Figure Test (RCFT)	Rey Complex Figure Test (RCFT) is a standardized test of visuospatial memory. Performance will be scored based on the delayed recall trial of the RCFT.	Baseline and 12 weeks after first exercise session

Collaborators and Investigators

• Sponsor: University of Southern California
• Investigators: Principal Investigator: Jonathan J Russin, MD, University of Southern California

Publications and helpful links

General Publications

• Gooch CL, Pracht E, Borenstein AR. The burden of neurological disease in the United States: A summary report and call to action. Ann Neurol. 2017 Apr;81(4):479-484. doi: 10.1002/ana.24897. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2022
• Primary Completion (Estimated): August 31, 2024
• Study Completion (Estimated): August 31, 2024

Study Registration Dates

• First Submitted: November 30, 2021
• First Submitted That Met QC Criteria: December 20, 2021
• First Posted (Actual): January 5, 2022

Study Record Updates

• Last Update Posted (Estimated): December 6, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Exercise; Neurogenesis; Cognition; Electrophysiology; Regeneration; Mesial temporal lobe epilepsy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes; Epilepsies, Partial; Epilepsy; Epilepsy, Temporal Lobe
• Other Study ID Numbers: APP-21-04349

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