Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05913401 |
| Other study ID # |
2304-001 |
| Secondary ID |
P20GM130452 |
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
February 1, 2024 |
| Est. completion date |
January 31, 2025 |
Study information
| Verified date |
March 2024 |
| Source |
Butler Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Given the growing evidence that aerobic increases cortical excitability and promotes
neuroplasticity, the scientific premise for its potential priming effect on the brain is
strong. Combining AE with rTMS may produce a neural environment optimized for a robust
physiological effect of rTMS, thereby leading to improved depression outcomes. With positive
findings, this study would provide preliminary support for an innovative, safe and feasible
approach for improving outcomes for this significant public health problem.
Description:
Depression is highly prevalent and a significant public health concern, resulting in
tremendous economic and societal burden. With first-line treatments leaving the majority of
patients with unremitted and impairing symptomatology, additional therapies to address
treatment-resistant depression (TRD) are critical. One such approach that has received
significant empirical attention is repetitive transcranial magnetic stimulation (rTMS). While
effective in reducing depression, rTMS's efficacy is not without limits, with remission rates
being less than 40%. Therefore, research focused on improving the efficacy of rTMS is timely
and critical for decreasing the overall public health burden of TRD. A putative mechanism of
the effect of rTMS on depression is through changes in electrophysiological properties of
neurons leading to increases in long-term potentiation (LTP) necessary for neuroplasticity.
In theory, it may be possible to improve rTMS outcomes by augmenting it with another
non-pharmacological treatment known to influence neuroplasticity. One innovative possibility
could be aerobic exercise (AE), as it has shown to result in increased neuroplasticity in
both animal and human studies and is known to reduce depression. There are a number of neural
effects of AE that could serve to prime the brain for rTMS including increased prefrontal
oxygenation and increased brain-derived neurotropic factor (BDNF, involved in inducing LTP).
Conceivably, bouts of AE just prior to rTMS sessions may create a neural environment that is
broadly primed for the more focally delivered TMS, potentially increasing its effectiveness.
To date, there have been no studies that have combined AE with rTMS. Therefore, the purpose
of the proposed study is to conduct the first test of AE priming among treatment-resistant
depressed individuals seeking rTMS treatment. We expect that AE will improve the efficacy of
rTMS through changes in exercise-induced neuroplasticity via measurements of motor-evoked
potential (MEP). Exercise studies have shown single bouts of aerobic activity can result in
increased MEP amplitudes and chronic AE (i.e., multi-sessions) decreases resting motor
thresholds (RMT; the lowest intensity of TMS that evokes a MEP), thereby increasing overall
cortical excitability. For the proposed pilot study, we will recruit N=30 patients with
treatment-resistant depression who are seeking rTMS treatment at Butler Hospital's TMS
Clinic. Participants will be randomized to engage in one of two different activities just
prior to their scheduled daily TMS treatments: 1) 20 minutes of supervised moderate-intensity
AE on an on-site treadmill (n=15) OR 2) 20-minutes of watching an educational video (n=15)
while sitting. To examine indicators of neuroplasticity, a TMS cortical excitability protocol
(assessing plasticity through measuring MEPs generated by single and paired magnetic pulses)
will be conducted at baseline (prior to initiating the course of rTMS) and then again after
30 rTMS treatment sessions. At these same timepoints, depression severity will be measured
using the Inventory of Depressive Symptomatology-Self Report scale (IDS-SR). The feasibility
and acceptability of the combined AE+TMS approach will also be examined to inform the design
of a future larger trial.
