Trial Outcomes & Findings for iTBS Study for Depression (Randomized) (NCT NCT03745768)

Results Overview

We will assess the efficacy of iTBS in improving mood by determining if older adults randomized to iTBS will show significant decreases in the Montgomery-Asberg Depression Rating Scale consistent with improvement of depressive symptoms. The total score for the scale will be reported. The total scores range is 0 - 60 with 0 = minimum score and 60 the maximum score. A low score is better as it denotes less depressive symptoms.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

19 participants

Primary outcome timeframe

6 weeks

Results posted on

2022-07-06

Participant Flow

Participant milestones

Participant milestones
Measure	Active iTBS Treatment Intermittent theta burst stimulation to the dorsolateral prefrontal cortex Intermittent Theta Burst Stimulation: Intermittent theta burst stimulation delivered to the dorsolateral prefrontal cortex on the left and right sides of the brain.	Sham Stimulation Sham stimulation to the dorsolateral prefrontal cortex. Intermittent Theta Burst Stimulation: Intermittent theta burst stimulation delivered to the dorsolateral prefrontal cortex on the left and right sides of the brain.
Overall Study STARTED	10	9
Overall Study COMPLETED	8	9
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Active iTBS Treatment Intermittent theta burst stimulation to the dorsolateral prefrontal cortex Intermittent Theta Burst Stimulation: Intermittent theta burst stimulation delivered to the dorsolateral prefrontal cortex on the left and right sides of the brain.	Sham Stimulation Sham stimulation to the dorsolateral prefrontal cortex. Intermittent Theta Burst Stimulation: Intermittent theta burst stimulation delivered to the dorsolateral prefrontal cortex on the left and right sides of the brain.
Overall Study discontinued study	2	0

Baseline Characteristics

iTBS Study for Depression (Randomized)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Active iTBS Treatment n=8 Participants Intermittent theta burst stimulation to the dorsolateral prefrontal cortex Intermittent Theta Burst Stimulation: Intermittent theta burst stimulation delivered to the dorsolateral prefrontal cortex on the left and right sides of the brain.	Sham Stimulation n=9 Participants Sham stimulation to the dorsolateral prefrontal cortex. Intermittent Theta Burst Stimulation: Intermittent theta burst stimulation delivered to the dorsolateral prefrontal cortex on the left and right sides of the brain.	Total n=17 Participants Total of all reporting groups
Age, Continuous	66 years STANDARD_DEVIATION 5 • n=5 Participants	67 years STANDARD_DEVIATION 5 • n=7 Participants	67 years STANDARD_DEVIATION 5 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	6 Participants n=7 Participants	8 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Montgomery Asberg Depression Scale	23.75 units on a scale STANDARD_DEVIATION 5.52 • n=5 Participants	20.88 units on a scale STANDARD_DEVIATION 3.88 • n=7 Participants	22.23 units on a scale STANDARD_DEVIATION 4.8 • n=5 Participants

PRIMARY outcome

Timeframe: 6 weeks

We will assess the efficacy of iTBS in improving mood by determining if older adults randomized to iTBS will show significant decreases in the Montgomery-Asberg Depression Rating Scale consistent with improvement of depressive symptoms. The total score for the scale will be reported. The total scores range is 0 - 60 with 0 = minimum score and 60 the maximum score. A low score is better as it denotes less depressive symptoms.

Outcome measures

Outcome measures
Measure	Active iTBS Treatment n=8 Participants Intermittent theta burst stimulation to the dorsolateral prefrontal cortex Intermittent Theta Burst Stimulation: Intermittent theta burst stimulation delivered to the dorsolateral prefrontal cortex on the left and right sides of the brain.	Sham Stimulation n=9 Participants Sham stimulation to the dorsolateral prefrontal cortex. Intermittent Theta Burst Stimulation: Intermittent theta burst stimulation delivered to the dorsolateral prefrontal cortex on the left and right sides of the brain.
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Scores From Baseline to the End of the Intervention	10.25 score on a scale Standard Deviation 6.40	13.33 score on a scale Standard Deviation 3.70

PRIMARY outcome

Timeframe: 6 weeks

Improvement in executive function in participants will be assessed by determining if subjects randomized to iTBS show significant increases in their NIH Toolbox Flanker Inhibitory control and attention test from baseline to the end of 6 weeks, compared to those randomized to sham. NIH Tool box Flanker inhibitory control and attention test is a validated instrument measuring attention and inhibitory control. The age corrected standard score is used, for which the normative mean is 100 and the standard deviation is 15. This score compares the score of the test taker to those in the NIH tool box nationally representative sample at the same age, where a score of 100 indicates performance that was at the national average for the test-taking participant's age. A score of 115 or 85 for example would indicate that the participant's performance is 1SD above or below the national average respectively, when compared with like-aged participants. Higher scores indicate higher performance.

Outcome measures

Outcome measures
Measure	Active iTBS Treatment n=8 Participants Intermittent theta burst stimulation to the dorsolateral prefrontal cortex Intermittent Theta Burst Stimulation: Intermittent theta burst stimulation delivered to the dorsolateral prefrontal cortex on the left and right sides of the brain.	Sham Stimulation n=9 Participants Sham stimulation to the dorsolateral prefrontal cortex. Intermittent Theta Burst Stimulation: Intermittent theta burst stimulation delivered to the dorsolateral prefrontal cortex on the left and right sides of the brain.
Change in the NIH Toolbox Executive Domain Measure Flanker Inhibitory Control and Attention Test	1.38 score on a scale Standard Deviation 8.7	0.78 score on a scale Standard Deviation 7.42

PRIMARY outcome

Timeframe: 6 weeks

Improvement in executive function in participants will be assessed by determining if subjects randomized to iTBS show significant increases in their NIH Toolbox Dimensional change card sort test from baseline to the end of 6 weeks, compared to those randomized to sham. NIH Tool box Dimensional change card sort test is a validated instrument measuring cognitive flexibility. The age corrected standard score is used, for which the normative mean is 100 and the standard deviation is 15. This score compares the score of the test taker to those in the NIH tool box nationally representative sample at the same age, where a score of 100 indicates performance that was at the national average for the test-taking participant's age. A score of 115 or 85 for example would indicate that the participant's performance is 1SD above or below the national average respectively, when compared with like-aged participants. Higher scores indicate higher performance.

Outcome measures

Outcome measures
Measure	Active iTBS Treatment n=8 Participants Intermittent theta burst stimulation to the dorsolateral prefrontal cortex Intermittent Theta Burst Stimulation: Intermittent theta burst stimulation delivered to the dorsolateral prefrontal cortex on the left and right sides of the brain.	Sham Stimulation n=9 Participants Sham stimulation to the dorsolateral prefrontal cortex. Intermittent Theta Burst Stimulation: Intermittent theta burst stimulation delivered to the dorsolateral prefrontal cortex on the left and right sides of the brain.
Change in the NIH Tool Box Executive Measure Dimensional Change Card Sort Test	1.00 score on a scale Standard Deviation 10.98	-1.67 score on a scale Standard Deviation 11.02

PRIMARY outcome

Timeframe: 6 weeks

Improvement in executive function in participants will be assessed by determining if subjects randomized to iTBS show significant increases in their NIH Toolbox list sorting working memory test from baseline to the end of 6 weeks, compared to those randomized to sham. NIH Tool box list sorting working memory test is a validated instrument measuring working memory. The age corrected standard score is used, for which the normative mean is 100 and the standard deviation is 15. This score compares the score of the test taker to those in the NIH tool box nationally representative sample at the same age, where a score of 100 indicates performance that was at the national average for the test-taking participant's age. A score of 115 or 85 for example would indicate that the participant's performance is 1SD above or below the national average respectively, when compared with like-aged participants. Higher scores indicate higher performance.

Outcome measures

Outcome measures
Measure	Active iTBS Treatment n=8 Participants Intermittent theta burst stimulation to the dorsolateral prefrontal cortex Intermittent Theta Burst Stimulation: Intermittent theta burst stimulation delivered to the dorsolateral prefrontal cortex on the left and right sides of the brain.	Sham Stimulation n=9 Participants Sham stimulation to the dorsolateral prefrontal cortex. Intermittent Theta Burst Stimulation: Intermittent theta burst stimulation delivered to the dorsolateral prefrontal cortex on the left and right sides of the brain.
Change in the NIH Tool Box List Sorting Working Memory Measure	-0.88 score on a scale Standard Deviation 10.77	-7.00 score on a scale Standard Deviation 14.22

PRIMARY outcome

Timeframe: 6 weeks

We will test the effects of iTBS on functional connectivity within the CNN ( fronto-parietal network) in depressed older adults obtained using resting state fMRI measuring BOLD signal in the brain. Depressed older adults randomized to iTBS versus sham will have a significant increase in functional connectivity within the fronto-parietal network from baseline to week 6.

Outcome measures

Outcome measures
Measure	Active iTBS Treatment n=8 Participants Intermittent theta burst stimulation to the dorsolateral prefrontal cortex Intermittent Theta Burst Stimulation: Intermittent theta burst stimulation delivered to the dorsolateral prefrontal cortex on the left and right sides of the brain.	Sham Stimulation n=9 Participants Sham stimulation to the dorsolateral prefrontal cortex. Intermittent Theta Burst Stimulation: Intermittent theta burst stimulation delivered to the dorsolateral prefrontal cortex on the left and right sides of the brain.
Connectivity Change Within the CNN, Fronto-parietal Network	0.0059 correlation coefficient Standard Deviation 0.0295	0.0153 correlation coefficient Standard Deviation 0.0347

PRIMARY outcome

Timeframe: 6 weeks

We will test the effects of iTBS on functional connectivity within the CNN cingulo opercular network in depressed older adults obtained using resting state fMRI measuring bold signal in the brain. Depressed older adults randomized to iTBS versus sham will have a significant increase in functional connectivity within the cingulo-opercular network from baseline to week 6.

Outcome measures

Outcome measures
Measure	Active iTBS Treatment n=8 Participants Intermittent theta burst stimulation to the dorsolateral prefrontal cortex Intermittent Theta Burst Stimulation: Intermittent theta burst stimulation delivered to the dorsolateral prefrontal cortex on the left and right sides of the brain.	Sham Stimulation n=9 Participants Sham stimulation to the dorsolateral prefrontal cortex. Intermittent Theta Burst Stimulation: Intermittent theta burst stimulation delivered to the dorsolateral prefrontal cortex on the left and right sides of the brain.
Connectivity Change Within the CNN, Cingulo Opercular Network	-0.0070 correlation coefficient Standard Deviation 0.0329	0.0076 correlation coefficient Standard Deviation 0.0578

Adverse Events

Active iTBS Treatment

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Sham Stimulation

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Pilar Cristancho M.D.

Washington University School of Medicine St. Louis

Phone: 314 362 2413

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place