Trial Outcomes & Findings for rTMS to Improve Cognitive Function in TBI (NCT NCT02152540)

Last Updated: 2021-01-15

Results Overview

The primary hypothesis is that Veterans receiving active rTMS will show improvement more than sham treated Veterans in performance between baseline and last assessment of \>1 SD on the Trail Making Test part B. This test is known for its accurate assessment of executive function in mild and moderate TBI. The TMT is a timed test and the goal is to complete the test as accurately and as quickly as possible. Raw scores are reported in seconds to complete the test. For Part B, an average score is 75 seconds and a deficient score is greater than 273 seconds. The present study reports T-scores, which can range from a minimum of 0 and a maximum of 100. The higher the T- score achieved by a participant, the better the performance, indicating a higher level of functioning.

Recruitment status

COMPLETED

Study phase

Target enrollment

33 participants

Primary outcome timeframe

Baseline (up to two weeks after screening visit); Post-Treatment (2 weeks from end of Baseline up to one month from entering the study but always the day of last treatment)

Results posted on

2021-01-15

Participant Flow

Participant milestones

Participant milestones
Measure	rTMS Those receiving experimental treatment will receive 20 sessions of rTMS. The treatment will be delivered by trained medical personnel. rTMS: Repetitive Transcranial Magnetic Stimulation	Sham rTMS Those receiving the sham rTMS will receive 20 sessions of sham rTMS. The treatment will be delivered by trained medical personnel. Sham rTMS: Placebo Device that simulates active rTMS treatment
Overall Study STARTED	17	16
Overall Study COMPLETED	17	16
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

rTMS to Improve Cognitive Function in TBI

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	rTMS n=17 Participants Those receiving experimental treatment will receive 20 sessions of rTMS. The treatment will be delivered by trained medical personnel. rTMS: Repetitive Transcranial Magnetic Stimulation	Sham rTMS n=16 Participants Those receiving the sham rTMS will receive 20 sessions of sham rTMS. The treatment will be delivered by trained medical personnel. Sham rTMS: Placebo Device that simulates active rTMS treatment	Total n=33 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	17 Participants n=5 Participants	16 Participants n=7 Participants	33 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	49.4 years STANDARD_DEVIATION 13.3 • n=5 Participants	39.4 years STANDARD_DEVIATION 11.9 • n=7 Participants	44.4 years STANDARD_DEVIATION 12.6 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	16 Participants n=7 Participants	28 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	8 Participants n=7 Participants	19 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	17 Participants n=5 Participants	16 Participants n=7 Participants	33 Participants n=5 Participants
Trails B T-score	52.1 T-score STANDARD_DEVIATION 8.2 • n=5 Participants	45.3 T-score STANDARD_DEVIATION 14.9 • n=7 Participants	48.7 T-score STANDARD_DEVIATION 11.6 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline (up to two weeks after screening visit); Post-Treatment (2 weeks from end of Baseline up to one month from entering the study but always the day of last treatment)

Outcome measures

Outcome measures
Measure	rTMS n=17 Participants Those receiving experimental treatment will receive 20 sessions of rTMS. The treatment will be delivered by trained medical personnel. rTMS: Repetitive Transcranial Magnetic Stimulation	Sham rTMS n=16 Participants Those receiving the sham rTMS will receive 20 sessions of sham rTMS. The treatment will be delivered by trained medical personnel. Sham rTMS: Placebo Device that simulates active rTMS treatment
Trail Making Test Part B Baseline	52.1 T-score Standard Error 14.9	45.3 T-score Standard Error 13.7
Trail Making Test Part B post-treatment	52.9 T-score Standard Error 8.2	50.8 T-score Standard Error 10.3

SECONDARY outcome

Timeframe: 6-month post treatment follow up

Population: All 25 Veterans met criteria for mild and moderate TBI based on the VA/DOD definition and a neurologist's physical exam.

Hypothesis: At the end of the 6 month post treatment followup TBI patients who received rTMS would be more likely to continue to have greater "executive function improvement" on Trail making test part B than patients who received Sham rTMS. Outcome measures Description: Trials B T-score range 0-75; higher scores indicate better performance on T-score

Outcome measures

Outcome measures
Measure	rTMS n=12 Participants Those receiving experimental treatment will receive 20 sessions of rTMS. The treatment will be delivered by trained medical personnel. rTMS: Repetitive Transcranial Magnetic Stimulation	Sham rTMS n=13 Participants Those receiving the sham rTMS will receive 20 sessions of sham rTMS. The treatment will be delivered by trained medical personnel. Sham rTMS: Placebo Device that simulates active rTMS treatment
Sustained Improvement on Executive Function	51.3 T-score Standard Deviation 5.4	51.2 T-score Standard Deviation 12.9

SECONDARY outcome

Timeframe: baseline and immediately post treatment (~two weeks)

Population: All 33 Veterans met criteria for mild and moderate TBI based on the VA/DOD definition and a neurologist's physical exam. All patients went through baseline testing that collected demographic (including military history etc.), neuropsychological and self-report questionnaires for health problems.

The Veterans RAND 36 Item Health Survey (VR-36©) is a brief, generic, multi-use, self-administered health surveys comprised of 36 items The instruments are primarily used to measure health-related quality of life, to estimate disease burden and to evaluate disease-specific impact on general and selected populations. The items on the questionnaire correspond to eight principal health domains including general health perceptions, physical functioning, role limitations due to physical and emotional problems, bodily pain, energy-fatigue , social functioning and mental health. higher scores mean better health and depicted in percentages. This scale would show significantly greater improvement in patients with mild to moderate TBI who received rTMS treatment. Outcome variable description: Scores for each domain are from 0-100 with a higher score defining a more favorable health outcome.

Outcome measures

Outcome measures
Measure	rTMS n=17 Participants Those receiving experimental treatment will receive 20 sessions of rTMS. The treatment will be delivered by trained medical personnel. rTMS: Repetitive Transcranial Magnetic Stimulation	Sham rTMS n=16 Participants Those receiving the sham rTMS will receive 20 sessions of sham rTMS. The treatment will be delivered by trained medical personnel. Sham rTMS: Placebo Device that simulates active rTMS treatment
Change in Quality of Life (QOL) Scale	59.0 score on a scale Standard Deviation 23.1	58.1 score on a scale Standard Deviation 25.7

SECONDARY outcome

Timeframe: Baseline only

Moderators of response Post Traumatic Stress Disorder (PTSD) as measured by PTSD Checklist- Military. The Score range is 17-85; higher scores indicate more severe symptoms.

Outcome measures

Outcome measures
Measure	rTMS n=17 Participants Those receiving experimental treatment will receive 20 sessions of rTMS. The treatment will be delivered by trained medical personnel. rTMS: Repetitive Transcranial Magnetic Stimulation	Sham rTMS n=16 Participants Those receiving the sham rTMS will receive 20 sessions of sham rTMS. The treatment will be delivered by trained medical personnel. Sham rTMS: Placebo Device that simulates active rTMS treatment
Moderators of Response: PTSD Score	41.8 score on the scale Standard Deviation 19.4	38.7 score on the scale Standard Deviation 11.8

SECONDARY outcome

Timeframe: post treatment (2 weeks) and 6-months

Population: We only analyzed 12 participants MRI scans in each group (Active and sham) because some data was lost due to MRI server issue. We are providing Beta scores means and stand below that are from the FMRI connectivity analysis from post treatment to 6-months in Sham and Active groups.

Each participant went under an MRI scan at post treatment (2 weeks) and 6-months. Functional MRI measures the Blood Oxygen Level Dependent (BOLD) signal in the brain and it can change with this brain stimulation. One common way to address this change or response to treatment is to measure the connectivity between BOLD signal of a network, such as the established default mode network, with the stimulation site. This is provided as a correlation value between the two points- and the strength of correlation is used for each participant at each time point to see if any change has occurred due to stimulation (active vs. placebo). Beta Values are provided below.

Outcome measures

Outcome measures
Measure	rTMS n=12 Participants Those receiving experimental treatment will receive 20 sessions of rTMS. The treatment will be delivered by trained medical personnel. rTMS: Repetitive Transcranial Magnetic Stimulation	Sham rTMS n=12 Participants Those receiving the sham rTMS will receive 20 sessions of sham rTMS. The treatment will be delivered by trained medical personnel. Sham rTMS: Placebo Device that simulates active rTMS treatment
Treatment Induced Change in Functional Connectivity	-0.81 beta coefficient Standard Error 0.12	0.34 beta coefficient Standard Error 0.15

SECONDARY outcome

Timeframe: baseline and post treatment (2 weeks)

Population: We present the mean ratio of Brain Derived Neurotrophic Factor (BDNF)/Pro-BDNF in Active vs. Sham groups from baseline to post treatment

Mediator of response to treatment: to establish a preliminary understanding of the underlying mechanisms related to rTMS modulation of synaptic repair in TBI we will also look at the change from baseline and post treatment in brain-derived neurotrophic factor (BDNF) samples in our population. Outcome Measure description: mean of BDNF/ProBDNF ratio measured in blood (ng/ml) will be provided

Outcome measures

Outcome measures
Measure	rTMS n=17 Participants Those receiving experimental treatment will receive 20 sessions of rTMS. The treatment will be delivered by trained medical personnel. rTMS: Repetitive Transcranial Magnetic Stimulation	Sham rTMS n=16 Participants Those receiving the sham rTMS will receive 20 sessions of sham rTMS. The treatment will be delivered by trained medical personnel. Sham rTMS: Placebo Device that simulates active rTMS treatment
Change in a Mediator of Response: Brain Derived Neurotrophic Factor (BDNF)	-0.31 ratio of BDNF/Pro-BDNF Standard Deviation 3.02	0.25 ratio of BDNF/Pro-BDNF Standard Deviation 3.10

Adverse Events

rTMS

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Sham rTMS

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	rTMS n=17 participants at risk Those receiving experimental treatment will receive 20 sessions of rTMS. The treatment will be delivered by trained medical personnel. rTMS: Repetitive Transcranial Magnetic Stimulation	Sham rTMS n=16 participants at risk Those receiving the sham rTMS will receive 20 sessions of sham rTMS. The treatment will be delivered by trained medical personnel. Sham rTMS: Placebo Device that simulates active rTMS treatment
Eye disorders Pain behind R eye for 5 minutes	5.9% 1/17 • Number of events 1 • 6 months (from first rTMS treatment to 6 month follow up)	0.00% 0/16 • 6 months (from first rTMS treatment to 6 month follow up)
Ear and labyrinth disorders Sensation of decreased hearing acuity, pt realized was more "aware" of hearing	5.9% 1/17 • Number of events 1 • 6 months (from first rTMS treatment to 6 month follow up)	0.00% 0/16 • 6 months (from first rTMS treatment to 6 month follow up)
Eye disorders Pressure behind eyes and headache starting after baseline MRI, resolved in 3 days during first treat	5.9% 1/17 • Number of events 1 • 6 months (from first rTMS treatment to 6 month follow up)	0.00% 0/16 • 6 months (from first rTMS treatment to 6 month follow up)
Musculoskeletal and connective tissue disorders Exacerbation of low back pain, resolved in 3 days w medication	5.9% 1/17 • Number of events 1 • 6 months (from first rTMS treatment to 6 month follow up)	0.00% 0/16 • 6 months (from first rTMS treatment to 6 month follow up)
Eye disorders Stimulation-induced eye lid and facial twitching due to improper coil positioning, resolved in secs	5.9% 1/17 • Number of events 1 • 6 months (from first rTMS treatment to 6 month follow up)	0.00% 0/16 • 6 months (from first rTMS treatment to 6 month follow up)
Vascular disorders Headache after treatment, resolved same day w/out treatment	5.9% 1/17 • Number of events 1 • 6 months (from first rTMS treatment to 6 month follow up)	0.00% 0/16 • 6 months (from first rTMS treatment to 6 month follow up)
Endocrine disorders hematoma at surgery site after parathyroidectomy, unrelated to study participation	5.9% 1/17 • Number of events 1 • 6 months (from first rTMS treatment to 6 month follow up)	0.00% 0/16 • 6 months (from first rTMS treatment to 6 month follow up)

Additional Information

Dr. Maheen M. Adamson

DVBIC, VA Palo Alto/Stanford School of Medicine

Phone: 6502136307

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place