rTMS to Enhance Cognitive Performance and Promote Resilience

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the most effective dose of brief, non-invasive brain stimulation (repetitive transcranial magnetic stimulation, rTMS) for improving cognitive functions such as attention and memory as well as to improve the ability to recover from stressful situations (stress resilience).

Detailed Description
-----------------
Repetitive transcranial magnetic stimulation (rTMS) works by rapidly turning a focused magnetic field on-and-off repeatedly over your head, which passes directly through your hair, scalp, and skull and onto your brain, and can temporarily increase brain activity under the magnetic field. Repetitive transcranial magnetic stimulation (rTMS) is an FDA approved treatment for depression, and is used commonly to treat people for their depression. The rTMS treatment regime used in this study is different from the FDA approved treatment because you will receive up to ten treatments per day over five days instead of the FDA approved rTMS treatment regime of 25 treatments over 25 days. This sort of accelerated or high dose protocol has been shown to be safe and effective in the treatment of depression. We are hoping to find out if this treatment can be used as a treatment for improving cognitive function and stress resilience.

Official Title
-----------------
Safety and Efficacy of an Accelerated Protocol of Intermittent Theta Burst Transcranial Magnetic Stimulation (TMS) to Enhance Performance and Promote Resilience in Astronauts: Study 1

Conditions
-----------------
Cognition, Stress Reaction

Intervention / Treatment
-----------------
* Device: rTMS


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: No history of mental or physical illness No implanted metal in the body College graduates (Associates degree or higher) Negative urine pregnancy test, if female subject of childbearing potential Able to read and understand questionnaires and informed consent Exclusion Criteria: Any current psychiatric diagnosis or current Clinical Global Impression ratings of psychiatric illness > 1 Current physical illness History of CNS disease, concussion, overnight hospitalization, tumors, seizures, meningitis, encephalitis, abnormal CT/MRI of the brain Moderate to severe traumatic brain injury (TBI) History of a continuing significant laboratory finding Frequent or severe headaches Any history of psychotropic medication prior to study enrollment Females of childbearing potential who are pregnant (by urine HCG), nursing, or who are not using a reliable form of birth control. active participation or plan for enrollment in another evidence-based clinical trial affecting psychosocial function repeated abuse or dependence upon drugs (excluding nicotine and caffeine) implanted devices/ferrous metal of any kind

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose 1<br>All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 1 is 5 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds. | Device: rTMS<br>* Device: Repetitive Transcranial Magnetic Stimulation (rTMS) MagVenture MagPro TMS System would be utilized to deliver 3-minute sessions of intermittent theta burst to left dorsolateral prefrontal cortex.<br>|
| Experimental: Dose 2<br>All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 2 is 10 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds. | Device: rTMS<br>* Device: Repetitive Transcranial Magnetic Stimulation (rTMS) MagVenture MagPro TMS System would be utilized to deliver 3-minute sessions of intermittent theta burst to left dorsolateral prefrontal cortex.<br>|
| Experimental: Dose 3<br>All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 3 is 15 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds. | Device: rTMS<br>* Device: Repetitive Transcranial Magnetic Stimulation (rTMS) MagVenture MagPro TMS System would be utilized to deliver 3-minute sessions of intermittent theta burst to left dorsolateral prefrontal cortex.<br>|
| Experimental: Dose 4<br>All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 4 is 20 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds. | Device: rTMS<br>* Device: Repetitive Transcranial Magnetic Stimulation (rTMS) MagVenture MagPro TMS System would be utilized to deliver 3-minute sessions of intermittent theta burst to left dorsolateral prefrontal cortex.<br>|
| Experimental: Dose 5<br>All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 5 is 25 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds. | Device: rTMS<br>* Device: Repetitive Transcranial Magnetic Stimulation (rTMS) MagVenture MagPro TMS System would be utilized to deliver 3-minute sessions of intermittent theta burst to left dorsolateral prefrontal cortex.<br>|
| Experimental: Dose 6<br>All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 6 is 30 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds. | Device: rTMS<br>* Device: Repetitive Transcranial Magnetic Stimulation (rTMS) MagVenture MagPro TMS System would be utilized to deliver 3-minute sessions of intermittent theta burst to left dorsolateral prefrontal cortex.<br>|
| Experimental: Dose 7<br>All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 7 is 35 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds. | Device: rTMS<br>* Device: Repetitive Transcranial Magnetic Stimulation (rTMS) MagVenture MagPro TMS System would be utilized to deliver 3-minute sessions of intermittent theta burst to left dorsolateral prefrontal cortex.<br>|
| Experimental: Dose 8<br>All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 8 is 40 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds. | Device: rTMS<br>* Device: Repetitive Transcranial Magnetic Stimulation (rTMS) MagVenture MagPro TMS System would be utilized to deliver 3-minute sessions of intermittent theta burst to left dorsolateral prefrontal cortex.<br>|
| Experimental: Dose 9<br>All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 9 is 45 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds. | Device: rTMS<br>* Device: Repetitive Transcranial Magnetic Stimulation (rTMS) MagVenture MagPro TMS System would be utilized to deliver 3-minute sessions of intermittent theta burst to left dorsolateral prefrontal cortex.<br>|
| Experimental: Dose 10<br>All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 10 is 50 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds. | Device: rTMS<br>* Device: Repetitive Transcranial Magnetic Stimulation (rTMS) MagVenture MagPro TMS System would be utilized to deliver 3-minute sessions of intermittent theta burst to left dorsolateral prefrontal cortex.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Score of Neurocognitive Performance | Participants would complete a computerized batteries (Penn Computerized Neuropsychological Battery and NIH Cognition Battery). Tasks would assess the following domains: information-processing speed, executive function, sustained attention/vigilance, verbal memory, working-memory capacity, inhibition/impulsivity, and sensorimotor function. | Baseline (Day 1) | 
| Change from baseline in Neurocognitive Performance at 1 week post treatment | Participants would complete a computerized batteries (Penn Computerized Neuropsychological Battery and NIH Cognition Battery). Tasks would assess the following domains: information-processing speed, executive function, sustained attention/vigilance, verbal memory, working-memory capacity, inhibition/impulsivity, and sensorimotor function. | Post-treatment (within 1 week of completing rTMS) | 
| Change from baseline in Neurocognitive Performance at 1 month post treatment | Participants would complete a computerized batteries (Penn Computerized Neuropsychological Battery and NIH Cognition Battery). Tasks would assess the following domains: information-processing speed, executive function, sustained attention/vigilance, verbal memory, working-memory capacity, inhibition/impulsivity, and sensorimotor function. | Post-treatment (within 1 month of completing rTMS) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Score of Stress Resilience as assessed by Connor Davidson Resilience Scale | Participants would complete a series of questionnaires 1. Connor Davidson Resilience Scale -Questions are rated on a scale from 0-4, where a higher score reflects greater resilience. | Baseline (Day 1) | 
| Mean Score of Stress Resilience as assessed by Perceived Stress Scale-10 | Participants would complete a series of questionnaires 2. Perceived Stress Scale-10 -Questions are rated on a scale from 0-4, where a higher score reflects a higher perceived stress. | Baseline (Day 1) | 
| Mean Score of Stress Resilience as assessed by Inventory of Depression and Anxiety Symptoms-II | Participants would complete a series of questionnaires 3. Inventory of Depression and Anxiety Symptoms-II -Questions are rated on a scale from 1-5 and covers a wide array of psychological measures | Baseline (Day 1) | 
| Mean Score of Stress Resilience as assessed by Connor Davidson Resilience Scale | Participants would complete a series of questionnaires 1. Connor Davidson Resilience Scale -Questions are rated on a scale from 0-4, where a higher score reflects greater resilience. | Post-treatment (within 1 week of completing rTMS) | 
| Mean Score of Stress Resilience as assessed by Perceived Stress Scale-10 | Participants would complete a series of questionnaires 2. Perceived Stress Scale-10 -Questions are rated on a scale from 0-4, where a higher score reflects a higher perceived stress. | Post-treatment (within 1 week of completing rTMS) | 
| Mean Score of Stress Resilience as assessed by Inventory of Depression and Anxiety Symptoms-II | Participants would complete a series of questionnaires 3. Inventory of Depression and Anxiety Symptoms-II -Questions are rated on a scale from 1-5 and covers a wide array of psychological measures | Post-treatment (within 1 week of completing rTMS) | 
| Mean Score of Stress Resilience as assessed by Connor Davidson Resilience Scale | Participants would complete a series of questionnaires 1. Connor Davidson Resilience Scale -Questions are rated on a scale from 0-4, where a higher score reflects greater resilience. | Post-treatment (within 1 month of completing rTMS) | 
| Mean Score of Stress Resilience as assessed by Perceived Stress Scale-10 | Participants would complete a series of questionnaires 2. Perceived Stress Scale-10 -Questions are rated on a scale from 0-4, where a higher score reflects a higher perceived stress. | Post-treatment (within 1 month of completing rTMS) | 
| Mean Score of Stress Resilience as assessed by Inventory of Depression and Anxiety Symptoms-II | Participants would complete a series of questionnaires 3. Inventory of Depression and Anxiety Symptoms-II -Questions are rated on a scale from 1-5 and covers a wide array of psychological measures | Post-treatment (within 1 month of completing rTMS) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
memory, cognition, adult, prefrontal cortex, Transcranial Magnetic Stimulation, Stress, Psychological, attention