Clinical trial NCT05179083: Exercise for Brain Regeneration in Epilepsy
Official title: Regenerating the Adult Human Brain Through Exercise
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Temporal Lobe Epilepsy
Keywords: Exercise
Neurogenesis
Mesial temporal lobe epilepsy
Regeneration
Cognition
Electrophysiology
Lead sponsor: University of Southern California
Sponsor class: OTHER
First posted: 2022-01-05
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Adherence to exercise and assessments
timeFrame: Through study completion, an average of 6 months
Secondary outcomes:
measure: Neurogenesis
timeFrame: 13 weeks after first exercise session
measure: Rey Auditory Verbal Learning Test (RAVLT) - Trial V
timeFrame: Baseline and 12 weeks after first exercise session
measure: Rey Auditory Verbal Learning Test (RAVLT) - Summary score
timeFrame: Baseline and 12 weeks after first exercise session
measure: WAIS-IV - Matrix Reasoning
timeFrame: Baseline and 12 weeks after first exercise session
measure: Rey Complex Figure Test (RCFT)
timeFrame: Baseline and 12 weeks after first exercise session
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California Department of Neurosurgery
state: California
Study officials:
affiliation: University of Southern California
name: Jonathan J Russin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.