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Exercise for Brain Regeneration in Epilepsy

Phase 1
Recruiting
Conditions
Temporal Lobe Epilepsy
Interventions
Other: High-Impact Aerobic Exercise
Other: Low-Impact Aerobic Exercise
Registration Number
NCT05179083
Lead Sponsor
University of Southern California
Brief Summary

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.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
10
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
High-impact ExerciseHigh-Impact Aerobic Exercise-
Low-impact ExerciseLow-Impact Aerobic Exercise-
Primary Outcome Measures
NameTimeMethod
Adherence to exercise and assessmentsThrough study completion, an average of 6 months

Number of completed exercise and assessment sessions

Secondary Outcome Measures
NameTimeMethod
Rey Auditory Verbal Learning Test (RAVLT) - Summary scoreBaseline and 12 weeks after first exercise session

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.

Neurogenesis13 weeks after first exercise session

Number of new neurons per mm3 in surgically resected tissue after cell culture

Rey Auditory Verbal Learning Test (RAVLT) - Trial VBaseline and 12 weeks after first exercise session

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.

WAIS-IV - Matrix ReasoningBaseline and 12 weeks after first exercise session

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.

Rey Complex Figure Test (RCFT)Baseline and 12 weeks after first exercise session

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.

Trial Locations

Locations (1)

University of Southern California Department of Neurosurgery

🇺🇸

Los Angeles, California, United States

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