Effects of Accelerated rTMS on Cognitive Function
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age50-90
SponsorSan Francisco Neurology and Sleep Center
About this trial
Cognitive impairment, including mild cognitive impairment (MCI) and mild dementia, is a growing public health challenge with limited effective treatment options. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique that has shown promise for improving cognitive function, but most studies have used conventional protocols and relied on global screening tools that may not capture domain-specific changes.
The purpose of this study is to evaluate the efficacy and tolerability of repetitive transcranial magnetic stimulation (rTMS) delivered via the EXOMIND™ device (BTL-699-2) for improving cognitive function in adults aged 50 to 90 years with mild to moderate cognitive impairment. The study asks whether a course of 6 rTMS sessions targeting the left dorsolateral prefrontal cortex, administered twice weekly over approximately 3 weeks, can produce meaningful and sustained improvements in global and domain-specific cognitive function over a 3-month follow-up period.
This is a single-center, open-label, prospective pilot study enrolling 80 participants with documented cognitive decline (Montreal Cognitive Assessment \[MoCA\] score 10-25). Participants will receive 6 sessions of high frequency rTMS (6,300 pulses per session at alternating frequencies of 12, 15, and 18 Hz) over approximately 3 weeks. The primary outcome is the change from baseline in MoCA score at 1-month follow-up. Secondary outcomes include changes in MoCA score at post-treatment and 3-month follow-up, changes in domain-specific cognitive measures (visual spatial working memory, episodic memory, deductive reasoning, mental rotation, verbal short term memory, and attention) assessed by the Creyos cognitive battery, and changes in depressive symptoms measured by the Patient Health Questionnaire-9 (PHQ-9). Assessments are performed at baseline, post treatment, 1-month follow-up, and 3-month follow-up. Total study duration per participant is up to 139 days.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Subject must be 50 to 90 years of age, inclusive, on the day of signing informed consent.
Ability to provide written informed consent, or availability of a legally authorized representative to provide consent.
Subject must sign an ICF indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.
Sufficient visual and auditory acuity to complete cognitive assessments.
Disqualifiers
Electronic implants in or near the head - rTMS devices are contraindicated for use in patients who have active or inactive implants in or near the head including device leads, deep brain stimulators, cochlear implants, ocular implants, and vagus nerve stimulators, implanted devices such as cardiac pacemakers, defibrillators, and neurostimulators.
Metallic, ferromagnetic, or other magnetic-sensitive implants/objects in or near the head - rTMS devices are contraindicated for use in patients who have conductive, ferromagnetic, or other magnetic-sensitive metals implanted in their head (with some exceptions in the mouth - see Operator's Manual) or within 12 inches (30 cm) of the therapy coil. Examples include implanted electrodes/stimulators, aneurysm clips or coils, stents, bullet fragments, jewelry, hair barrettes, and tattoos with metallic ink.
Drug pumps within 12 inches (30 cm) of the therapy coil.
Inability to determine the motor threshold of the participant (i.e., the minimum stimulus required to induce contraction of the right thumb cannot be established).
Trial design
Design model
Single group
Treatments tested in this trial
TMS
DeviceThe EXOMIND™ (BTL-699-2) is a repetitive transcranial magnetic stimulation (rTMS) device that delivers targeted electromagnetic pulses to cortical brain regions. In this study, stimulation is applied to the left dorsolateral prefrontal cortex (DLPFC), a region implicated in executive function, working memory, and attention. The DLPFC target is localized using the standard 5-cm rule, measured anterior to the motor cortex hot spot. Each treatment session uses a multi-frequency protocol alternating between 12, 15, and 18 Hz stimulation frequencies, delivering a total of 6,300 pulses over 24 minutes and 30 seconds. Stimulation intensity is calibrated to each participant's resting motor threshold, defined as the minimum stimulus intensity required to produce a visible contraction of the right abductor pollicis brevis muscle. Six sessions are administered twice weekly over approximately 3 weeks. The procedure is performed on
Treatment groups
80 Participants
are divided into 1 treatment groupGroup A: rTMS TreatmentActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
Change from baseline in the Montreal Cognitive Assessment (MoCA) score at 1-month follow-up.
The Montreal Cognitive Assessment (MoCA) is a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Total Score Range: 0 to 30. Interpretation: Higher scores indicate better cognitive function (a score of 26 or above is generally considered normal). Metric: The change is calculated by subtracting the baseline score from the 1-month follow-up score.
Time frame
From baseline to the 1-month follow upSecondary outcomes
1
Change from baseline in the Montreal Cognitive Assessment (MoCA) score at the last treatment session
The Montreal Cognitive Assessment (MoCA) is a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Total Score Range: 0 to 30. Interpretation: Higher scores indicate better cognitive function (a score of 26 or above is generally considered normal). Metric: The change is calculated by subtracting the baseline score from the 1-month follow-up score.
Time frame
From baseline to the end of treatment (approximately Day 21)2
Change from baseline in the Montreal Cognitive Assessment (MoCA) score at the 3-month follow-up visit
The Montreal Cognitive Assessment (MoCA) is a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Total Score Range: 0 to 30. Interpretation: Higher scores indicate better cognitive function (a score of 26 or above is generally considered normal). Metric: The change is calculated by subtracting the baseline score from the 1-month follow-up score.
Time frame
From baseline to the end of treatment at 3-month follow-up3
Change from baseline in the following domain-specific cognitive measures assessed by the Creyos cognitive battery at the last treatment session
Cognitive performance will be assessed using the Creyos online platform. This measure evaluates specific cognitive domains through validated tasks. For this study, the following domains and their corresponding primary metrics are assessed: Memory (Monkey Ladders Task): Measures visuospatial working memory. Reasoning (Odd One Out Task): Measures deductive reasoning and fluid intelligence. Concentration (Feature Match Task): Measures attention and mental processing speed. Planning (Spatial Planning Task): Measures executive function and strategy. Scoring Parameters: Scale Title: Creyos Cognitive Assessment Score (Standardized Score). Minimum and Maximum Values: Scores are standardized with a mean of 100 and a standard deviation of 15. While theoretically open-ended, the effective range for clinical reporting is typically 0 to 150. Interpretation: Higher scores mean a better outcome, indicating superior cognitive performance relative to the normative database. Metric: The change
Time frame
From baseline to the end of treatment (approximately Day 21)4
Change from baseline in the following domain-specific cognitive measures assessed by the Creyos cognitive battery at the 1-month follow-up
Cognitive performance will be assessed using the Creyos online platform. This measure evaluates specific cognitive domains through validated tasks. For this study, the following domains and their corresponding primary metrics are assessed: Memory (Monkey Ladders Task): Measures visuospatial working memory. Reasoning (Odd One Out Task): Measures deductive reasoning and fluid intelligence. Concentration (Feature Match Task): Measures attention and mental processing speed. Planning (Spatial Planning Task): Measures executive function and strategy. Scoring Parameters: Scale Title: Creyos Cognitive Assessment Score (Standardized Score). Minimum and Maximum Values: Scores are standardized with a mean of 100 and a standard deviation of 15. While theoretically open-ended, the effective range for clinical reporting is typically 0 to 150. Interpretation: Higher scores mean a better outcome, indicating superior cognitive performance relative to the normative database. Metric: The change
Time frame
From baseline to the end of treatment at 1-month follow-upSponsors and contacts
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Source ClinicalTrials.gov