Efficacy of Repetitive Transcranial Magnetic Stimulation for Improvement of Memory in Older Adults With TBI

Aging Clinical Trial

Official title: Efficacy of Repetitive Transcranial Magnetic Stimulation for Improvement of Memory in Older Adults With TBI

Status Completed

Clinical Trial Summary

The proposed study will evaluate the safety, durability and efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) as a promising non-invasive therapeutic treatment for improving memory in older adults with mild or moderate Traumatic Brain Injury (TBI) who have been experiencing residual memory or cognitive problems that affect daily functioning.

Clinical Trial Description

Recent advances in both AD and TBI test non-pharmaceutical interventions that target chronic symptom improvement (e.g., non- invasive brain stimulation, exercise and cognitive training). In order to provide targeted therapies to patients who suffer from chronic sequela of TBI it is necessary to understand mechanisms of repair within the context of an aging brain. Repetitive TMS (rTMS) delivers therapeutic, noninvasive brain stimulation, is FDA-approved for treatment for major depression and currently used for treatment of pain, PTSD, anxiety, improvement of executive function in mild and moderate TBI, severe TBI, memory enhancement and dementia.

This treatment can induce neuronal long-term potentiation resulting in synaptic repair leading to improvements in memory function through hippocampal- cortical circuits and brain connectivity measured by resting state-fMRI (rs fMRI) particularly in default mode and central executive network (DMN & CEN). The study primarily proposes to assess the efficacy of rTMS to improve memory performance and to test rs-fMRI (i.e. DMN) as a potential biomarker to capture response to treatment in older patients suffering with chronic symptoms related to previous brain injuries (depression, PTSD etc). In addition, the study will assess other established biomarkers longitudinally (e.g.,hypometabolism via PET FDG, cortical oscillation via electroencephalography (EEG), Brain Derived Nerve Growth Factor (BDNF)and hippocampal volume from structural MRI) to capture patient response to treatment that may signal early dementia.

HYPOTHESES:

Primary:

Subjects with TBI who receive active rTMS treatment (rTMS_A) will: a) show significantly greater improvement from baseline in memory performance post rTMS intervention compared to subjects who received sham rTMS treatment (rTMS_S), and b) show stronger functional connectivity within and between DMN and CEN post rTMS intervention compared to patients who received sham (rTMS_S).

Secondary:

1. Quality of Life (QOL): scores on QOL scale will improve with rTMS treatment in patients who receive rTMS treatment.

2. Sustained Improvement: At 6-month follow-up, patients with TBI in rTMS_A group would be more likely to have sustained greater brain connectivity compared to patients in the rTMS_S group predicting better memory performance.

3. Moderators of Response: The following variables may moderate memory function improvement in patients with TBI post intervention and at 6-month follow-up: Age, health condition variables (severity of symptoms at baseline, time to injury, baseline cognitive performance, TBI type,comorbidities (PTSD, sleep, depression), substance abuse, medication use, fatigue); physiological and biological variables (baseline hippocampal volume and/or microstructure, baseline connectivity in DMN & CEN, EEG resting and task-related cortical oscillations, and Brain Derived Neurotrophic Factor (BDNF) genotype.

4. Mediators of Response: To assess the mechanism of rTMS in synaptic repair/regeneration, pre and post changes will be assessed in depression and PTSD measures, Plasma BDNF, FDG PET hypometabolism in precuneus/posterior cingulate area, EEG resting and task-related cortical oscillations, and connectivity of DLPFC (stimulation site & part of CEN) with other DMN.

SPECIFIC OBJECTIVES:

Primary Objective: a) To assess the efficacy of rTMS to predict improvement in memory performance pre and post rTMS intervention in older patients with TBI, and b) To assess rs-fMRI as a biomarker to detect these changes in memory performance.

Secondary Objective: To assess the mechanism of rTMS in synaptic repair/regeneration by assessment of structure & functional brain activity (PET/MRI, fMRI, & EEG), genetic, cognitive and behavioral function factors (including QOL, depression and PTSD). ;

Related Conditions & MeSH terms

• Aging
• Brain Injuries
• Brain Injuries, Traumatic
• Memory Deficits
• Memory Disorders
• Repetitive Transcranial Magnetic Stimulation

• NCT number: NCT03727737
• Study type: Interventional
• Source: Palo Alto Veterans Institute for Research
• Status: Completed
• Phase: N/A
• Start date: October 23, 2018
• Completion date: September 14, 2022