Trial Outcomes & Findings for Accelerated rTMS for Post-Stroke Apathy (NCT NCT05878457)

A total of 21 participants provided informed consent and were considered enrolled. Of these, 6 participants were excluded prior to treatment initiation due to ineligibility or withdrawal. Fifteen participants were assigned to the intervention and initiated treatment.

Of 21 participants who provided informed consent (enrolled), 6 were excluded prior to treatment initiation due to MRI contraindications (n=3), failure to meet apathy inclusion criteria (n=1), new neurological diagnosis (n=1), and claustrophobia (n=1). Fifteen participants met eligibility criteria and were assigned to the intervention and initiated treatment.

Accelerated rTMS for Post-Stroke Apathy

The Lille Apathy Rating Scale (LARS) is a validated 33-item structured interview assessing apathy across 9 domains, including intellectual curiosity, emotion, action initiation, self-awareness, productivity, interests, novelty seeking, motivation, and social engagement. Total scores range from -36 to +36, with higher scores indicating greater severity of apathy (worse outcome) and lower (more negative) scores indicating less apathy (better outcome). The total score is calculated by summing responses across all items and domains to generate a composite score.

A review of systems questionnaire (Intermittent Theta Burst Stimulation Review of Systems; iTBS ROS) was administered repeatedly during each treatment day to assess treatment-emergent symptoms. Symptoms were rated on a scale from 0 to 5 (0 = none, 1 = minimal, 2 = mild, 3 = moderate, 4 = marked, 5 = severe), with higher scores indicating greater symptom severity (worse outcome). Values reported represent the average symptom severity across all assessments collected during the 3 treatment days for each participant, and then averaged across participants.

The Montreal Cognitive Assessment (MoCA) is a clinical assessment of cognitive function. The MoCA assesses multiple cognitive domains including memory, visuospatial skills, executive function, attention, concentration, calculation, language, abstraction, and orientation. The MoCA can be administered in approximately 10 minutes and total scores range from 0 to 30 with lower scores correlating with greater degree of cognitive impairment.

Fluid cognition was measured using the iPad-administered NIH Toolbox Cognition Battery (NIHTB-CB). Fluid Cognition Composite scores were calculated by averaging the demographically adjusted (age, education, sex, race/ethnicity; Casaletto et al., 2015) T-scores for 5 NIHTB-CB tests: the flanker inhibitory control, list sorting working memory, pattern comparison processing speed, dimensional change card sort tests, and picture sequence memory. T-Scores have a mean of 50 and a standard deviation of 10. Lower scores indicate worse performance. There are no established thresholds or cutoffs for clinically distinct or diagnostic categories.

Percentage of participants who completed the study relative to all participants who initiated treatment

The Apathy Evaluation Scale (AES) clinically validated rating scale assessing symptoms of apathy. The AES is comprised of 18 items rated on a four-point Likert-Scale assessing and quantifying emotional, behavioral and cognitive aspects of apathy. Total scores on the AES range from 18 to 72 with high scores correlating with greater severity of apathy.

The Patient-Reported Outcomes Measurement Information System (PROMIS) Depression Short Form is a validated patient-reported outcome measure assessing depressive symptoms, including negative mood, cognitive symptoms, and decreased positive affect. Scores are reported as T-scores standardized to the U.S. general population, where a T-score of 50 represents the population mean and 10 represents the standard deviation. Higher T-scores indicate greater depressive symptom severity (worse outcome), while lower T-scores indicate fewer depressive symptoms (better outcome). T-scores of approximately 60 or greater are generally considered indicative of at least mild clinically elevated depressive symptoms, with higher thresholds reflecting increasing severity.