Mild Cognitive Impairment
Conditions
Brief summary
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.
Interventions
DEVICEHigh-dose accelerated rTMS
A MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System will be utilized. All participants will receive open-label treatment for approximately eight, 3-minute sessions of intermittent theta burst rTMS on each of three days within an eight-day span. A single session = 600 pulses at 120% resting motor threshold (rMT), intermittent Theta Burst Stimulation (iTBS) triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 s to left dorsolateral prefrontal cortex. Total pulses = 14,400. To enable adherence and retention, the days do not need to be contiguous. Same day sessions will be separated by 10-15 minutes, but more accounting for participant comfort.
Sponsors
National Center of Neuromodulation for Rehabilitation
Medical University of South Carolina
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
65 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Age 60-85 * English as a first/primary language * Has been diagnosed with MCI by a healthcare provider within the past two years per National Institute on Aging - Alzheimer's Association (NIA-AA) criteria: (1) Concern regarding cognitive decline reported by patient, informant, or clinician, (2) Objective evidence of impairment for age in 1+ cognitive domains, typically memory, (3) Preserved independent function, (4) no dementia. * Has met actuarial neuropsychological criteria for amnestic MCI: (1) ≥2 impaired scores (i.e. ≤16th %ile) within one cognitive domain, or (2) ≥1 impaired scores (i.e. ≤16th %ile) in ≥3 cognitive domains, using demographically-corrected normative data. (1) and (2) must include the Memory domain. * The primary suspected etiology of amnestic MCI must be neurodegenerative, with competing differential diagnoses (e.g. psychiatric disorder, movement disorder, reversible causes, substance use) ruled out as the primary etiology/ies following a clinical evaluation by a healthcare provider. * Ability to provide independent informed consent, consistent with the MCI diagnostic criterion of preserved independent function.
Exclusion criteria
* Dementia diagnosis per the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) or NIA-AA criteria. * Daily/weekly use of anticholinergics, neuroleptics, sedatives, or bupropion. Stimulant use may be allowed pending investigator review. Cholinesterase inhibitors, NMDA receptor antagonists, and antidepressants are allowed if on a stable regimen of four weeks prior to enrollment. * History of significant or unstable condition/s that may impact cognition such as significant cardiac, cerebrovascular, or metabolic disease, severe mental illness (e.g. bipolar disorder, psychoses), alcohol or substance use disorder, developmental disorder, or other neurologic disease (e.g. severe brain injury, seizures). * MRI and TMS contraindications (e.g., implants, claustrophobia, conditions/treatments that lower seizure threshold, taking medications that have short half-lives, no quantifiable motor threshold, active substance use disorder, bipolar disorder). * Is enrolled in a clinical trial and/or has received an investigational medication within the last 30 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Retention Rate | 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). |
| Change From Baseline Global Cognition, as Measured by the Montreal Cognitive Assessment (MoCA) | 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. |
| Change in the Review of Systems Criteria Compared to Baseline | 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). |
| Patient Perception of Treatment Acceptability | 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. |
| Number of Participants With Clinically Significant Structural Brain Change on T1- and T2-weighted Magnetic Resonance Imaging (MRI) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline Depression, as Measured by the Geriatric Depression Scale (GDS) | 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. |
| Change From Baseline Cognition, as Measured by the Fluid Cognition Composite Score From the NIH Toolbox Cognition Battery | 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-treatment assessment. The statistical analysis compares this mean score to the mean score at Baseline. |
| Change From Baseline Depression, as Measured by the Hamilton Depression Rating Scale (HAM-D) | 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. |
Countries
United States
Participant flow
Recruitment details
Participants were referred by neurologists and neuropsychologists at MUSC's outpatient memory disorders and neuropsychology clinics. They were recruited between 12/22/2020 and 5/5/2022. The first participant was enrolled on 4/12/2021 and the last participant was enrolled on 6/1/2022.
Pre-assignment details
Of the 67 participants assessed for eligibility, 10 did not meet inclusion criteria, 15 met exclusion criteria, 17 declined to participate, and 1 was excluded for other reasons. 24 participants were assigned to treatment.
Participants by arm
| Arm | Count |
|---|---|
| High-dose Accelerated rTMS High-dose accelerated rTMS: A MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System will be utilized. All participants will receive open-label treatment for approximately eight, 3-minute sessions of intermittent theta burst rTMS on each of three days within an eight-day span. A single session = 600 pulses at 120% rMT, intermittent Theta Burst Stimulation (iTBS) triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 s to left dorsolateral prefrontal cortex. Total pulses = 14,400. To enable adherence and retention, the days do not need to be contiguous. Same day sessions will be separated by 10-15 minutes, but more accounting for participant comfort. | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | High-dose Accelerated rTMS |
|---|---|
| Age, Continuous | 74.1 years STANDARD_DEVIATION 5.71 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Fluid Cognition Composite | 40.25 T-score STANDARD_DEVIATION 8.07 |
| Geriatric Depression Scale (GDS) | 4.55 scores on a scale STANDARD_DEVIATION 3.14 |
| Hamilton Depression Rating Scale (HAM-D) | .24 scores on a scale STANDARD_DEVIATION 0.77 |
| Montreal Cognitive Assessment (MoCA) | -1.25 Z-score STANDARD_DEVIATION 1.38 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 24 |
| other Total, other adverse events | 0 / 24 |
| serious Total, serious adverse events | 0 / 24 |
Outcome results
Primary
Change From Baseline Global Cognition, as Measured by the Montreal Cognitive Assessment (MoCA)
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.
Time frame: Baseline prior to treatment and at follow-up within 1 week post-treatment
Population: Participants who completed both the pre- and post-treatment assessments were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High-dose Accelerated rTMS | Change From Baseline Global Cognition, as Measured by the Montreal Cognitive Assessment (MoCA) | -1.20 Z-score | Standard Deviation 1.18 |
p-value: 0.725t-test, 2 sided
Primary
Change in the Review of Systems Criteria Compared to Baseline
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).
Time frame: Baseline prior to treatment and at follow-up within 1 week post-treatment
Population: Participants who completed both the pre- and post-treatment assessments were included in this analysis.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Loss of dexterity: Post-Treatment | Marked/severe (4-5) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Hearing changes: Post-Treatment | Minimal/none (0-1) | 19 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Hearing changes: Post-Treatment | Mild/moderate (2-3) | 2 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Nausea/Vomiting: Post-Treatment | Marked/severe (4-5) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Appetite loss: Treatment day 1 (Baseline) | Minimal/none (0-1) | 21 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Appetite loss: Post-Treatment | Mild/moderate (2-3) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Appetite loss: Post-Treatment | Marked/severe (4-5) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Hearing changes: Post-Treatment | Marked/severe (4-5) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Vision changes: Treatment day 1 (Baseline) | Minimal/none (0-1) | 21 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Vision changes: Treatment day 1 (Baseline) | Mild/moderate (2-3) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Vision changes: Treatment day 1 (Baseline) | Marked/severe (4-5) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Vision changes: Post-Treatment | Minimal/none (0-1) | 21 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Vision changes: Post-Treatment | Mild/moderate (2-3) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Vision changes: Post-Treatment | Marked/severe (4-5) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Hearing changes: Treatment day 1 (Baseline) | Minimal/none (0-1) | 21 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Hearing changes: Treatment day 1 (Baseline) | Mild/moderate (2-3) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Hearing changes: Treatment day 1 (Baseline) | Marked/severe (4-5) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Ear ringing: Treatment day 1 (Baseline) | Minimal/none (0-1) | 21 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Ear ringing: Treatment day 1 (Baseline) | Mild/moderate (2-3) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Ear ringing: Treatment day 1 (Baseline) | Marked/severe (4-5) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Ear ringing: Post-Treatment | Minimal/none (0-1) | 20 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Ear ringing: Post-Treatment | Mild/moderate (2-3) | 1 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Ear ringing: Post-Treatment | Marked/severe (4-5) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Nausea/Vomiting: Treatment day 1 (Baseline) | Minimal/none (0-1) | 21 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Nausea/Vomiting: Treatment day 1 (Baseline) | Mild/moderate (2-3) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Nausea/Vomiting: Treatment day 1 (Baseline) | Marked/severe (4-5) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Nausea/Vomiting: Post-Treatment | Minimal/none (0-1) | 21 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Nausea/Vomiting: Post-Treatment | Mild/moderate (2-3) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Appetite loss: Treatment day 1 (Baseline) | Mild/moderate (2-3) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Appetite loss: Treatment day 1 (Baseline) | Marked/severe (4-5) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Appetite loss: Post-Treatment | Minimal/none (0-1) | 21 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Rash: Treatment day 1 (Baseline) | Minimal/none (0-1) | 21 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Rash: Treatment day 1 (Baseline) | Mild/moderate (2-3) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Rash: Treatment day 1 (Baseline) | Marked/severe (4-5) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Rash: Post-Treatment | Minimal/none (0-1) | 21 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Rash: Post-Treatment | Mild/moderate (2-3) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Rash: Post-Treatment | Marked/severe (4-5) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Skin changes: Treatment day 1 (Baseline) | Minimal/none (0-1) | 21 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Skin changes: Treatment day 1 (Baseline) | Mild/moderate (2-3) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Skin changes: Treatment day 1 (Baseline) | Marked/severe (4-5) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Skin changes: Post-Treatment | Minimal/none (0-1) | 21 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Skin changes: Post-Treatment | Mild/moderate (2-3) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Skin changes: Post-Treatment | Marked/severe (4-5) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Headache: Treatment day 1 (Baseline) | Mild/moderate (2-3) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Headache: Treatment day 1 (Baseline) | Minimal/none (0-1) | 21 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Headache: Treatment day 1 (Baseline) | Marked/severe (4-5) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Headache: Post-Treatment | Minimal/none (0-1) | 20 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Headache: Post-Treatment | Mild/moderate (2-3) | 1 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Headache: Post-Treatment | Marked/severe (4-5) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Scalp pain: Treatment day 1 (Baseline) | Minimal/none (0-1) | 21 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Scalp pain: Treatment day 1 (Baseline) | Mild/moderate (2-3) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Scalp pain: Treatment day 1 (Baseline) | Marked/severe (4-5) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Scalp pain: Post-Treatment | Minimal/none (0-1) | 19 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Scalp pain: Post-Treatment | Mild/moderate (2-3) | 2 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Scalp pain: Post-Treatment | Marked/severe (4-5) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Arm/hand pain: Treatment day 1 (Baseline) | Minimal/none (0-1) | 21 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Arm/hand pain: Treatment day 1 (Baseline) | Mild/moderate (2-3) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Arm/hand pain: Treatment day 1 (Baseline) | Marked/severe (4-5) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Arm/hand pain: Post-Treatment | Minimal/none (0-1) | 21 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Arm/hand pain: Post-Treatment | Mild/moderate (2-3) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Arm/hand pain: Post-Treatment | Marked/severe (4-5) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Other pain: Treatment day 1 (Baseline) | Minimal/none (0-1) | 21 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Other pain: Treatment day 1 (Baseline) | Mild/moderate (2-3) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Other pain: Treatment day 1 (Baseline) | Marked/severe (4-5) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Other pain: Post-Treatment | Minimal/none (0-1) | 20 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Other pain: Post-Treatment | Mild/moderate (2-3) | 1 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Other pain: Post-Treatment | Marked/severe (4-5) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Weakness: Treatment day 1 (Baseline) | Minimal/none (0-1) | 21 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Weakness: Treatment day 1 (Baseline) | Mild/moderate (2-3) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Weakness: Treatment day 1 (Baseline) | Marked/severe (4-5) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Weakness: Post-Treatment | Minimal/none (0-1) | 21 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Weakness: Post-Treatment | Mild/moderate (2-3) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Weakness: Post-Treatment | Marked/severe (4-5) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Loss of dexterity: Treatment day 1 (Baseline) | Minimal/none (0-1) | 21 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Loss of dexterity: Treatment day 1 (Baseline) | Mild/moderate (2-3) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Loss of dexterity: Treatment day 1 (Baseline) | Marked/severe (4-5) | 0 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Loss of dexterity: Post-Treatment | Minimal/none (0-1) | 21 Participants |
| High-dose Accelerated rTMS | Change in the Review of Systems Criteria Compared to Baseline | Loss of dexterity: Post-Treatment | Mild/moderate (2-3) | 0 Participants |
Primary
Number of Participants With Clinically Significant Structural Brain Change on T1- and T2-weighted Magnetic Resonance Imaging (MRI)
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.
Time frame: Baseline prior to treatment and at follow-up within 1 week post-treatment
Population: Participants who completed both the pre- and post-treatment assessments were included in this analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High-dose Accelerated rTMS | Number of Participants With Clinically Significant Structural Brain Change on T1- and T2-weighted Magnetic Resonance Imaging (MRI) | 0 Participants |
Primary
Patient Perception of Treatment Acceptability
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.
Time frame: Administered at post-treatment
Population: Participants who completed both the pre- and post-treatment assessments were included in this analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| High-dose Accelerated rTMS | Patient Perception of Treatment Acceptability | There was plenty of flexibility in scheduling rTMS sessions around my other obligations. | 5 score on a scale |
| High-dose Accelerated rTMS | Patient Perception of Treatment Acceptability | I was motivated to attend the rTMS sessions. | 5 score on a scale |
| High-dose Accelerated rTMS | Patient Perception of Treatment Acceptability | I was committed to completing the treatment course. | 5 score on a scale |
| High-dose Accelerated rTMS | Patient Perception of Treatment Acceptability | I was interested in the rTMS techniques and learning about them. | 5 score on a scale |
| High-dose Accelerated rTMS | Patient Perception of Treatment Acceptability | I understand the purpose of the treatment and how it could help my symptoms. | 5 score on a scale |
| High-dose Accelerated rTMS | Patient Perception of Treatment Acceptability | I would be open to completing another course of rTMS treatment in the future, if needed. | 5 score on a scale |
| High-dose Accelerated rTMS | Patient Perception of Treatment Acceptability | The rTMS treatment helped improve my ability to cope with daily challenges. | 3 score on a scale |
| High-dose Accelerated rTMS | Patient Perception of Treatment Acceptability | Paraphrased: Condensed treatment was preferable to conventional treatment course | 5 score on a scale |
| High-dose Accelerated rTMS | Patient Perception of Treatment Acceptability | The staff members were attentive and sensitive to my needs during treatment. | 5 score on a scale |
| High-dose Accelerated rTMS | Patient Perception of Treatment Acceptability | The staff members explained all procedures to me and answered my questions. | 5 score on a scale |
| High-dose Accelerated rTMS | Patient Perception of Treatment Acceptability | At times I wanted to quit treatment. | 1 score on a scale |
| High-dose Accelerated rTMS | Patient Perception of Treatment Acceptability | Treatment sessions were stressful. | 1 score on a scale |
| High-dose Accelerated rTMS | Patient Perception of Treatment Acceptability | It was hard to stay awake during the rTMS sessions. | 1 score on a scale |
| High-dose Accelerated rTMS | Patient Perception of Treatment Acceptability | I experienced pain and discomfort during treatment that was difficult to tolerate. | 1 score on a scale |
| High-dose Accelerated rTMS | Patient Perception of Treatment Acceptability | Completing multiple rTMS sessions in each day was at times tiring. | 1 score on a scale |
Primary
Retention Rate
Percentage of participants who completed the study (n=21) relative to all participants who initiated treatment (n=22).
Time frame: Baseline prior to treatment and at follow-up within 1 week post-treatment
Population: All participants who initiated treatment were included in this analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High-dose Accelerated rTMS | Retention Rate | 21 Participants |
Secondary
Change From Baseline Cognition, as Measured by the Fluid Cognition Composite Score From the NIH Toolbox Cognition Battery
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-treatment assessment. The statistical analysis compares this mean score to the mean score at Baseline.
Time frame: Baseline prior to treatment and at follow-up within 1 week post-treatment
Population: Participants who completed both the pre- and post-treatment assessments were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High-dose Accelerated rTMS | Change From Baseline Cognition, as Measured by the Fluid Cognition Composite Score From the NIH Toolbox Cognition Battery | 43.67 T-score | Standard Deviation 7.85 |
p-value: <0.001t-test, 2 sided
Secondary
Change From Baseline Depression, as Measured by the Geriatric Depression Scale (GDS)
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.
Time frame: Baseline prior to treatment and at follow-up within 1 week post-treatment
Population: Participants who completed both the pre- and post-treatment assessments were included in this analysis. Of the 21 participants who completed treatment, one was missing a GDS score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High-dose Accelerated rTMS | Change From Baseline Depression, as Measured by the Geriatric Depression Scale (GDS) | 4.65 scores on a scale | Standard Deviation 3.11 |
p-value: 0.897t-test, 2 sided
Secondary
Change From Baseline Depression, as Measured by the Hamilton Depression Rating Scale (HAM-D)
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.
Time frame: Baseline prior to treatment and at follow-up within 1 week post-treatment
Population: Participants who completed both the pre- and post-treatment assessments were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High-dose Accelerated rTMS | Change From Baseline Depression, as Measured by the Hamilton Depression Rating Scale (HAM-D) | .33 scores on a scale | Standard Deviation 0.91 |
p-value: 0.605t-test, 2 sided