Accelerated iTBS for Mild Cognitive Impairment
(PUSH2 Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Medical University of South Carolina
Must not be taking: Anticholinergics, Sedatives
Disqualifiers: Dementia, Bipolar, Schizophrenia, others
No Placebo Group
Trial Summary
What is the purpose of this trial?The goal of this phase II study is to establish the dose-response curves of a safe and clinically feasible non-invasive brain stimulation technique (accelerated Transcranial Magnetic Stimulation (TMS)) to improve both depression and cognitive function in Mild Cognitive Impairment (MCI) patients with comorbid depression. It is known that TMS can effectively treat depression. Identifying the right dose of accelerated TMS in MCI patients is necessary prior to designing subsequent trials to determine efficacy. These results will inform future clinical trials of accelerated TMS for MCI, with the long-term goal of developing an efficacious treatment to prevent dementia.
Will I have to stop taking my current medications?
The trial requires that you stay on a stable dose of your current medications for at least 4 weeks before joining. Some medications like anticholinergics or sedatives are not allowed, but others like antidepressants are okay if stable.
What data supports the effectiveness of the treatment Accelerated iTBS for Mild Cognitive Impairment?
Research suggests that repetitive transcranial magnetic stimulation (rTMS), which is similar to Accelerated iTBS, may help improve memory and cognitive function in patients with Alzheimer's disease and mild cognitive impairment by stimulating brain areas linked to memory.
12345Is accelerated iTBS safe for humans?
Repetitive transcranial magnetic stimulation (rTMS), which is similar to accelerated iTBS, has been studied in people with Alzheimer's disease and mild cognitive impairment. These studies suggest that rTMS is generally safe, as no major safety concerns were reported.
12678How is the Accelerated iTBS treatment different from other treatments for mild cognitive impairment?
Accelerated iTBS (intermittent Theta Burst Stimulation) is a form of transcranial magnetic stimulation (TMS) that uses magnetic fields to stimulate nerve cells in the brain, potentially improving memory and cognitive function. Unlike traditional treatments, it is non-invasive and focuses on enhancing brain plasticity (the brain's ability to change and adapt) by targeting specific brain regions associated with memory.
14579Eligibility Criteria
This trial is for people aged 60-85 with mild cognitive impairment (MCI) and moderate to severe depression. Participants must have a stable medication regimen, adequate mental and motor functions, an informant who knows them well, and meet specific neuropsychological criteria for MCI.Inclusion Criteria
English as a first/primary language
Met actuarial neuropsychological criteria for MCI within the past 2 years
I can move, feel, and speak well enough to complete tests.
+5 more
Exclusion Criteria
I have been diagnosed with dementia or a major thinking (cognitive) disorder.
A TICS score of ≤ 22 suggestive of dementia and a PHQ-9 score of 0-9
I've been on a stable dose of certain medications like antidepressants for over 4 weeks.
+5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive accelerated Transcranial Magnetic Stimulation (TMS) sessions to establish dose-response curves for depression and cognitive function improvement in MCI patients.
6 weeks
Daily sessions
Follow-up
Participants are monitored for safety and effectiveness after treatment, with assessments of cognitive and depression scales.
26 weeks
Assessments at Week 3, Week 10, and Week 26
Participant Groups
The study tests accelerated Transcranial Magnetic Stimulation (TMS), comparing it to a sham procedure to see if it can improve depression and cognitive function in MCI patients. The right TMS dose needs identification before larger trials on its effectiveness.
6Treatment groups
Experimental Treatment
Placebo Group
Group I: Dose Step 6 - 60 Active Accelerated iTBS SessionsExperimental Treatment1 Intervention
Participant will receive 10/10 active sessions and 0/10 sham sessions per day for a total of 60 active sessions (36,000 active pulses).
Group II: Dose Step 5 - 48 Active Accelerated iTBS SessionsExperimental Treatment2 Interventions
Participant will receive 8/10 active sessions and 2/10 sham sessions per day for a total of 48 active sessions (28,800 active pulses).
Group III: Dose Step 4 - 36 Active Accelerated iTBS SessionsExperimental Treatment2 Interventions
Participant will receive 6/10 active sessions and 4/10 sham sessions per day for a total of 36 active sessions (21,600 active pulses).
Group IV: Dose Step 3 - 24 Active Accelerated iTBS SessionsExperimental Treatment2 Interventions
Participant will receive 4/10 active sessions and 6/10 sham sessions per day for a total of 24 active sessions (14,400 active pulses).
Group V: Dose Step 2 - 12 Active Accelerated iTBS SessionsExperimental Treatment2 Interventions
Participant will receive 10 sessions of accelerated iTBS on each of 6 treatment days, including 2/10 active sessions and 8/10 sham sessions per day for a total of 12 active sessions (7,200 active pulses).
Group VI: Dose Step 1 - 0 Active Accelerated iTBS SessionsPlacebo Group1 Intervention
Participant will receive 10 sessions of accelerated iTBS on each of 6 treatment days, including 0/10 active sessions and 10/10 sham sessions per day for a total of 0 active sessions
Accelerated iTBS is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Transcranial Magnetic Stimulation for:
- Major Depressive Disorder (MDD)
- Obsessive-Compulsive Disorder (OCD)
- Migraines
- Smoking cessation
🇪🇺 Approved in European Union as Transcranial Magnetic Stimulation for:
- Major Depressive Disorder (MDD)
- Obsessive-Compulsive Disorder (OCD)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Medical University of South CarolinaCharleston, SC
Loading ...
Who Is Running the Clinical Trial?
Medical University of South CarolinaLead Sponsor
National Institute on Aging (NIA)Collaborator
References
Open-label, short-term, repetitive transcranial magnetic stimulation in patients with Alzheimer's disease with functional imaging correlates and literature review. [2014]Accumulating evidence suggests repetitive transcranial magnetic stimulation (rTMS) may be beneficial in ameliorating cognitive deficits in Alzheimer's disease (AD).
Cognitive effects and acceptability of non-invasive brain stimulation on Alzheimer's disease and mild cognitive impairment: a component network meta-analysis. [2021]To compare cognitive effects and acceptability of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) in patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI), and to determine whether cognitive training (CT) during rTMS or tDCS provides additional benefits.
Chronic treatment with rivastigmine in patients with Alzheimer's disease: a study on primary motor cortex excitability tested by 5 Hz-repetitive transcranial magnetic stimulation. [2015]To investigate changes in cortical excitability and short-term synaptic plasticity we delivered 5 Hz repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex in 11 patients with mild-to-moderate Alzheimer's disease (AD) before and after chronic therapy with rivastigmine.
Cognitive Improvement via Left Angular Gyrus-Navigated Repetitive Transcranial Magnetic Stimulation Inducing the Neuroplasticity of Thalamic System in Amnesic Mild Cognitive Impairment Patients. [2022]Stimulating superficial brain regions highly associated with the hippocampus by repetitive transcranial magnetic stimulation (rTMS) may improve memory of Alzheimer's disease (AD) spectrum patients.
Altered Cortical Synaptic Plasticity in Response to 5-Hz Repetitive Transcranial Magnetic Stimulation as a New Electrophysiological Finding in Amnestic Mild Cognitive Impairment Converting to Alzheimer's Disease: Results from a 4-year Prospective Cohort Study. [2023]To investigate cortical excitability and synaptic plasticity in amnestic mild cognitive impairment (aMCI) using 5 Hz repetitive transcranial magnetic stimulation (5 Hz-rTMS) and to assess whether specific TMS parameters predict conversion time to Alzheimer's disease (AD).
Effect of transcranial magnetic stimulation as an enhancer of cognitive stimulation sessions on mild cognitive impairment: Preliminary results. [2021]Mild cognitive impairment (MCI) is a state between normal cognition and dementia. Currently, there is little evidence of repetitive Transcranial Magnetic Stimulation (rTMS) as an enhancing tool for Cognitive Stimulation (CS) on MCI. The importance of this study consists in its assessment of the enhancing effect of rTMS on CS in 22 MCI patients randomized and divided into two group: active (AG) and sham (SG). Diagnoses and assessments were determined during 30 sessions over a 10-week period by Montreal Cognitive Assessment (MoCA) and Neuropsí test. Results were statistically significant in the intergroup analysis with MoCA and intragroup only for AG.
Repetitive Transcranial Magnetic Stimulation Induced Hypoconnectivity Within the Default Mode Network Yields Cognitive Improvements in Amnestic Mild Cognitive Impairment: A Randomized Controlled Study. [2020]Repetitive transcranial magnetic stimulation (rTMS) is thought to be effective in alleviating cognitive symptoms in patients with amnestic mild cognitive impairment (aMCI), but the mechanisms related to network modification are poorly understood.
Neuroimaging mechanisms of high-frequency repetitive transcranial magnetic stimulation for treatment of amnestic mild cognitive impairment: a double-blind randomized sham-controlled trial. [2021]Individuals with amnestic mild cognitive impairment (aMCI) have a high risk of developing Alzheimer's disease. Although repetitive transcranial magnetic stimulation (rTMS) is considered a potentially effective treatment for cognitive impairment in patients with aMCI, the neuroimaging mechanisms are poorly understood. Therefore, we performed a double-blind randomized sham-controlled trial in which rTMS was applied to the left dorsolateral prefrontal cortex of aMCI patients recruited from a community near the Third Hospital Affiliated to Sun Yat-sen University, China. Twenty-four patients with aMCI were randomly assigned to receive true rTMS (treatment group, n = 12, 6 men and 6 women; age 65.08 ± 4.89 years) or sham stimulation (sham group, n = 12, 5 men and 7 women; age 64.67 ± 4.77 years). rTMS parameters included a stimulation frequency of 10 Hz, stimulation duration of 2 seconds, stimulation interval of 8 seconds, 20 repetitions at 80% of the motor threshold, and 400 pulses per session. rTMS/sham stimulation was performed five times per week over a period of 4 consecutive weeks. Our results showed that compared with baseline, Montreal Cognitive Assessment scores were significantly increased and the value of the amplitude of low-frequency fluctuation (ALFF) was significantly increased at the end of treatment and 1 month after treatment. Compared with the sham group, the ALFF values in the right inferior frontal gyrus, triangular part of the inferior frontal gyrus, right precuneus, left angular gyrus, and right supramarginal gyrus were significantly increased, and the ALFF values in the right superior frontal gyrus were significantly decreased in the treatment group. These findings suggest that high-frequency rTMS can effectively improve cognitive function in aMCI patients and alter spontaneous brain activity in cognitive-related brain areas. This study was approved by the Ethics Committee of Shenzhen Baoan Hospital of Southern Medical University, China (approval No. BYL20190901) on September 3, 2019, and registered in the Chinese Clinical Trials Registry (registration No. ChiCTR1900028180) on December 14, 2019.
High-Frequency rTMS Could Improve Impaired Memory in Mild Cognitive Impairment Patients in China: A Randomized Controlled Study. [2023]The purpose of this study was to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) on improving memory deficits in mild cognitive impairment (MCI), as well as to provide visualized evidence for neuronal specificity by using resting-state functional magnetic resonance imaging.