NCT04503096: PUSH-Pilot

Plasticity Using Stimulation and Habit: A Pilot Open-label rTMS Study for MCI

Completed NA Results posted Last updated 7 September 2023

What this trial tests

NA trial testing High-dose accelerated rTMS in Mild Cognitive Impairment in 24 participants. Completed in 27 July 2022.

Timeline

12 April 2021

Primary endpoint
29 June 2022

27 July 2022

Quick facts

Lead sponsor	Medical University of South Carolina
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	24
Start date	12 April 2021
Primary completion	29 June 2022
Estimated completion	27 July 2022
Sites	1 location across United States

Drugs / interventions tested

• High-dose accelerated rTMS

Conditions studied

• Mild Cognitive Impairment — all drugs for Mild Cognitive Impairment →

Sponsor

Medical University of South Carolina

Who can join

Adults 65 to 85, any sex, with Mild Cognitive Impairment. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Clinically Significant Structural Brain Change on T1- and T2-weighted Magnetic Resonance Imaging (MRI) Primary · Baseline prior to treatment and at follow-up within 1 week post-treatment

Clinically significant structural brain change were determined by a board-certified neuroradiologist who reviewed both the pre-treatment and post-treatment structural (T1- and T2-weighted) MRI scans to identify the presence of any changes from pre- to post-treatment based on their clinical read of the images.

Group	Value	95% CI
High-dose Accelerated rTMS	0

Change From Baseline Global Cognition, as Measured by the Montreal Cognitive Assessment (MoCA) Primary · Baseline prior to treatment and at follow-up within 1 week post-treatment

The MoCA is a psychometrist-administered brief cognitive assessment tool with raw total scores ranging from 0 to 30, with higher values indicating better cognition. For this analysis raw total scores were converted to age- and education-adjusted Z-scores using published norms (Rossetti et al., 2011). Z-scores have a mean of 0 and a standard deviation of 1. Lower scores indicate worse performance. The outcome measure reported below is the mean Z-score score at the 1-week post-treatment assessment. The statistical analysis compares this mean score to the mean score at Baseline.

Group	Value	95% CI
High-dose Accelerated rTMS	-1.20	± 1.18

Change in the Review of Systems Criteria Compared to Baseline Primary · Baseline prior to treatment and at follow-up within 1 week post-treatment

A review of systems questionnaire will be administered to rate the subjective symptom (headache, scalp pain, arm/hand pain, other pain(s), numbness/tingling, other sensation(s), weakness, loss of dexterity, vision/hearing change(s), ear ringing, nausea/vomiting, appetite loss, rash, skin change(s) or any other symptom(s)) on a scale of 0 to 5 (none, minimal, mild, moderate, marked, severe).

Headache: Treatment day 1 (Baseline)

Group	Value	95% CI
High-dose Accelerated rTMS	21
High-dose Accelerated rTMS	0
High-dose Accelerated rTMS	0

Headache: Post-Treatment

Group	Value	95% CI
High-dose Accelerated rTMS	20
High-dose Accelerated rTMS	1
High-dose Accelerated rTMS	0

Scalp pain: Treatment day 1 (Baseline)

Group	Value	95% CI
High-dose Accelerated rTMS	21
High-dose Accelerated rTMS	0
High-dose Accelerated rTMS	0

Scalp pain: Post-Treatment

Group	Value	95% CI
High-dose Accelerated rTMS	19
High-dose Accelerated rTMS	2
High-dose Accelerated rTMS	0

Arm/hand pain: Treatment day 1 (Baseline)

Group	Value	95% CI
High-dose Accelerated rTMS	21
High-dose Accelerated rTMS	0
High-dose Accelerated rTMS	0

Arm/hand pain: Post-Treatment

Group	Value	95% CI
High-dose Accelerated rTMS	21
High-dose Accelerated rTMS	0
High-dose Accelerated rTMS	0

Other pain: Treatment day 1 (Baseline)

Group	Value	95% CI
High-dose Accelerated rTMS	21
High-dose Accelerated rTMS	0
High-dose Accelerated rTMS	0

Other pain: Post-Treatment

Group	Value	95% CI
High-dose Accelerated rTMS	20
High-dose Accelerated rTMS	1
High-dose Accelerated rTMS	0

Patient Perception of Treatment Acceptability Primary · Administered at post-treatment

A 15-item study-specific questionnaire of rTMS treatment acceptability, with each item rated on a scale from 1 to 5 (1 = not at all, 3 = somewhat, 5 = very much so). Higher scores indicate better acceptability for the first 10 items, lower scores indicate better acceptability for the last 5 items.

"I was motivated to attend the rTMS sessions."

Group	Value	95% CI
High-dose Accelerated rTMS	5	4 – 5

"I was committed to completing the treatment course."

Group	Value	95% CI
High-dose Accelerated rTMS	5	5 – 5

"I was interested in the rTMS techniques and learning about them."

Group	Value	95% CI
High-dose Accelerated rTMS	5	5 – 5

"I understand the purpose of the treatment and how it could help my symptoms."

Group	Value	95% CI
High-dose Accelerated rTMS	5	5 – 5

"I would be open to completing another course of rTMS treatment in the future, if needed."

Group	Value	95% CI
High-dose Accelerated rTMS	5	5 – 5

"The rTMS treatment helped improve my ability to cope with daily challenges."

Group	Value	95% CI
High-dose Accelerated rTMS	3	2 – 4

Paraphrased: Condensed treatment was preferable to conventional treatment course

Group	Value	95% CI
High-dose Accelerated rTMS	5	5 – 5

"The staff members were attentive and sensitive to my needs during treatment."

Group	Value	95% CI
High-dose Accelerated rTMS	5	5 – 5

Retention Rate Primary · Baseline prior to treatment and at follow-up within 1 week post-treatment

Percentage of participants who completed the study (n=21) relative to all participants who initiated treatment (n=22).

Group	Value	95% CI
High-dose Accelerated rTMS	21

Change From Baseline Depression, as Measured by the Hamilton Depression Rating Scale (HAM-D) Secondary · Baseline prior to treatment and at follow-up within 1 week post-treatment

The Hamilton Depression Rating Scale (Ham-D) is a 17-item interviewer-administered structured questionnaire designed to assess symptoms of depression with scores ranging from 0 to 53, with higher scores indicating more depressive symptoms. The outcome measure reported below is the mean score at the 1-week post-treatment assessment. The statistical analysis compares this mean score to the mean score at Baseline.

Group	Value	95% CI
High-dose Accelerated rTMS	.33	± .91

Change From Baseline Depression, as Measured by the Geriatric Depression Scale (GDS) Secondary · Baseline prior to treatment and at follow-up within 1 week post-treatment

The Geriatric Depression Scale (GDS) is a 30-item scale that evaluates the severity of depressive symptoms in older adults with scores ranging from 0 to 30, with higher scores indicating more depressive symptoms. The outcome measure reported below is the mean score at the 1-week post-treatment assessment. The statistical analysis compares this mean score to the mean score at Baseline.

Group	Value	95% CI
High-dose Accelerated rTMS	4.65	± 3.11

Change From Baseline Cognition, as Measured by the Fluid Cognition Composite Score From the NIH Toolbox Cognition Battery Secondary · Baseline prior to treatment and at follow-up within 1 week post-treatment

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 4 NIHTB-CB tests: the flanker inhibitory control, list sorting working memory, pattern comparison processing speed, and dimensional change card sort tests. T-Scores have a mean of 50 and a standard deviation of 10. Lower scores indicate worse performance. The outcome measure reported below is the mean T-score at the 1-week post-treat

Group	Value	95% CI
High-dose Accelerated rTMS	43.67	± 7.85

Sponsor's own description

The goal of this pilot study is to determine whether a high-dose form of non-invasive brain stimulation is a promising and safe treatment for Mild Cognitive Impairment (MCI). Transcranial magnetic stimulation (TMS) is an FDA approved treatment for depression. In studies of TMS for depression and other disorders, individuals have experienced improved cognitive function. Thus, the current study is testing whether TMS is safe, feasible and effective in improving cognition in individuals with MCI.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. A phase I trial of accelerated intermittent theta burst rTMS for amnestic MCI.
   Aghamoosa S, Lopez J, Rbeiz K, Fleischmann HH, et al · · 2024 · cited 7× · PMID 38719432 · DOI 10.1136/jnnp-2023-332680
2. Accelerated iTBS-Induced changes in resting-state functional connectivity correspond with cognitive improvement in amnestic MCI.
   Aghamoosa S, Nolin SA, Chen AA, Caulfield KA, et al · · 2025 · cited 1× · PMID 40252967 · DOI 10.1016/j.brs.2025.04.012