rTMS for Cognitive Impairment in Parkinson's Disease (TMSCogReP Trial)
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: VA Office of Research and Development
No Placebo Group
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?The purpose of this study is to examine safety, feasibility, and the behavioral and brain effects of a non-invasive treatment, repetitive transcranial magnetic stimulation (rTMS), for Veterans with Parkinson's disease or atypical parkinsonism and mild impairments in their thinking. The hypothesis is that rTMS can improve thinking for people with Parkinson's disease or atypical parkinsonism who are experiencing mild problems with their thinking ability.
What data supports the idea that rTMS for Cognitive Impairment in Parkinson's Disease is an effective treatment?The available research shows that repetitive transcranial magnetic stimulation (rTMS) has some positive effects on motor function in Parkinson's Disease, but it does not significantly improve cognitive function. One study found that rTMS improved daily activities and motor skills, like buttoning up clothes, when applied to the frontal part of the brain. Another study showed that rTMS helped improve reaction times and movement times in patients with Parkinson's Disease. However, a systematic review and meta-analysis indicated that while rTMS had a positive effect on motor function, it did not improve cognitive abilities. Therefore, while rTMS may help with movement issues, its effectiveness for cognitive impairment in Parkinson's Disease is not strongly supported by the current data.12367
Do I have to stop taking my current medications for this trial?No, you must stay on your current medications without changes in type or dose during the trial.
Is the treatment rTMS promising for cognitive impairment in Parkinson's disease?Yes, rTMS is a promising treatment for cognitive impairment in Parkinson's disease. Studies show that it can improve motor skills, daily activities, and cognitive functions by stimulating brain areas involved in movement and thinking. This non-invasive treatment helps the brain work better by enhancing its connectivity and function.125710
What safety data exists for rTMS in treating cognitive impairment in Parkinson's Disease?The safety of rTMS, including its variations like drTMS, has been evaluated in several studies. drTMS has been shown to be safely administered to patients with Parkinson's Syndromes, with variations in adverse event rates and severity. A review of TMS in Parkinson's Disease indicates a slight risk of seizures and other adverse events. Safety guidelines for rTMS have been established and updated, focusing on potential adverse events, screening precautions, and dosing considerations. Overall, rTMS is considered safe with proper guidelines and precautions.13489
Eligibility Criteria
This trial is for Veterans over 50 with Parkinson's disease who have mild cognitive impairment, can speak and read English, and are treated at Hines VA Hospital or Jesse Brown VA Medical Center. Participants must be on stable medication that won't change during the study. Those with severe depression, dementia, certain implants, history of seizures or metal in their body cannot join.Inclusion Criteria
I am 50 years old or older.
Exclusion Criteria
I am not taking medications known to increase the risk of seizures.
I have a shaking head when I am not moving it.
I have a brain condition that could make seizures more likely.
I have been diagnosed with congestive heart failure.
I or someone in my family has had seizures or epilepsy.
I have been diagnosed with severe depression.
I have had a stroke, head injury, or seizures without a known cause.
I have had deep brain stimulation surgery.
I am unable to make decisions for my own care.
My movements are too uncontrolled for clear imaging tests.
I have high pressure inside my skull.
Participant Groups
The trial tests if repetitive transcranial magnetic stimulation (rTMS) using a MagVenture MagProX100 stimulator can improve thinking abilities in those with Parkinson's experiencing mild cognitive issues. It assesses the safety and effects of rTMS on behavior and brain function.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: active rTMSExperimental Treatment1 Intervention
For active rTMS, a butterfly coil and MagVenture MagProX100 stimulator (MagVenture, Falun, Denmark) will be used. One rTMS session will consist of 40 trains of 5sec each at 110% of resting motor threshold and 15Hz will be provided at the left DLPFC.
Group II: sham rTMSPlacebo Group1 Intervention
For sham rTMS, the procedure will be carried out at the left DLPFC but a sham coil will be used. The MagVenture coil has an active side and a placebo side allowing a double-blind study to be conducted. The sham system looks, sounds and feels like active rTMS.
rTMS is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as rTMS for:
- Obsessive-Compulsive Disorder (OCD)
- Major Depressive Disorder
- Migraines
- Smoking cessation
🇪🇺 Approved in European Union as rTMS for:
- Obsessive-Compulsive Disorder (OCD)
- Major Depressive Disorder
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Jesse Brown VA Medical Center, Chicago, ILChicago, IL
Edward Hines Jr. VA Hospital, Hines, ILHines, IL
Loading ...
Who is running the clinical trial?
VA Office of Research and DevelopmentLead Sponsor
References
Akinesia in Parkinson's disease. II. Effects of subthreshold repetitive transcranial motor cortex stimulation. [2019]We studied the effects of repetitive transcranial stimulation of the motor cortex (rTMS) on choice reaction time (cRT), movement time (MT), and error rate (ER) in a serial reaction-time task in six medicated patients with Parkinson's disease (PD) and 10 age-matched normal controls. In normal subjects, subthreshold 5-Hz rTMS did not significantly change cRT, slightly shortened MT, but increased ER. In the patients, rTMS significantly shortened cRT and MT without affecting ER. These effects did not impair procedural learning. Performance on a grooved peg-board test was improved by rTMS in the same PD patients, especially when they were off medications, but worsened in the normal subjects. Repetitive, subthreshold motor cortex stimulation can improve performance in patients with PD and could be useful therapeutically.
Effects of successive repetitive transcranial magnetic stimulation on motor performances and brain perfusion in idiopathic Parkinson's disease. [2019]We studied the effects of 0.2 Hz repetitive transcranial magnetic stimulation (rTMS) successively performed 6 times for 2 weeks in 12 patients with idiopathic Parkinson's disease (PD). Ten patients received rTMS to the bilateral frontal cortex (frontal rTMS) and six patients received rTMS to the bilateral occipital cortex (occipital rTMS). Before and after rTMS, we evaluated regional cerebral blood flow (rCBF) using 99m-Tc-ECD single photon emission computed tomography (SPECT) and clinical tests. In an analysis with statistic parametric mapping, both frontal and occipital rTMS reduced rCBF in the cortical areas around the stimulated site. The activities of daily living (ADL) and motor scores of Unified Parkinson's Disease Rating Scale (UPDRS), pronation-supination movements, and buttoning up significantly improved after frontal rTMS than before it, while occipital rTMS had no significant effects in clinical tests.The findings of the present study suggest that successive 0.2 Hz rTMS has outlasting inhibitory effects on neuronal activity around the stimulated cortical areas. Because there were no significant relations between improved clinical tests and reduced rCBF, we speculate that the indirect effects of 0.2 Hz rTMS on subcortical structures are related to improved parkinsonian symptoms. Further studies recruiting large numbers of subjects are required to confirm the efficacy of 0.2 Hz rTMS on PD.
Controlled study of 50-Hz repetitive transcranial magnetic stimulation for the treatment of Parkinson disease. [2021]To investigate the safety and efficacy of 50-Hz repetitive transcranial magnetic stimulation (rTMS) in the treatment of motor symptoms in Parkinson disease (PD).
Safety of transcranial magnetic stimulation in Parkinson's disease: a review of the literature. [2021]Transcranial magnetic stimulation (TMS) has been used in both physiological studies and, more recently, the therapy of Parkinson's disease (PD). Prior TMS studies in healthy subjects and other patient populations demonstrate a slight risk of seizures and other adverse events. Our goal was to estimate these risks and document other safety concerns specific to PD patients.
Excitatory deep repetitive transcranial magnetic stimulation with H-coil as add-on treatment of motor symptoms in Parkinson's disease: an open label, pilot study. [2018]Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a potential treatment for Parkinson's disease (PD). H-coils, inducing deeper and wider magnetic fields compared to traditional coils, may be potentially useful in PD, characterized by widespread, bilateral involvement of cortico-subcortical circuits.
Using non-invasive transcranial stimulation to improve motor and cognitive function in Parkinson's disease: a systematic review and meta-analysis. [2022]Parkinson's disease (PD) is a neurodegenerative disorder affecting motor and cognitive abilities. There is no cure for PD, therefore identifying safe therapies to alleviate symptoms remains a priority. This meta-analysis quantified the effectiveness of repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (TES) to improve motor and cognitive dysfunction in PD. PubMed, EMBASE, Web of Science, Google Scholar, Scopus, Library of Congress and Cochrane library were searched. 24 rTMS and 9 TES studies (n = 33) with a sham control group were included for analyses. The Physiotherapy Evidence Database and Cochrane Risk of Bias showed high quality (7.5/10) and low bias with included studies respectively. Our results showed an overall positive effect in favour of rTMS (SMD = 0.394, CI [0.106-0.683], p = 0.007) and TES (SMD = 0.611, CI [0.188-1.035], p = 0.005) compared with sham stimulation on motor function, with no significant differences detected between rTMS and TES (Q [1] = 0.69, p = 0.406). Neither rTMS nor TES improved cognition. No effects for stimulation parameters on motor or cognitive function were observed. To enhance the clinical utility of non-invasive brain stimulation (NBS), individual prescription of stimulation parameters based upon symptomology and resting excitability state should be a priority of future research.
Effect of rTMS on Parkinson's cognitive function: a systematic review and meta-analysis. [2021]To evaluate the effects and optimal parameters of repetitive transcranial magnetic stimulation (rTMS) on cognition function of patients with Parkinson's disease (PD) and to estimate which cognitive function may obtain more benefits from rTMS.
Safety of Deep Repetitive Transcranial Magnetic Stimulation (drTMS) against Medical Refractory Symptoms in Parkinson Syndromes: First German Real-World Data with a Specific H5 Coil. [2022]So far, deep repetitive transcranial magnetic stimulation (drTMS) has shown promising results as an add-on treatment for Parkinson's disease (PD) but not for non-idiopathic Parkinson Syndromes (PS). We aimed to investigate the safety and feasibility of drTMS application in patients with different Parkinson Syndromes and medical refractory symptoms. Multifaceted real-world data (n = 21) were retrospectively analyzed regarding adverse effects as well as short-term effects of the drTMS treatment on patients' self-rated symptom severity and motor, cognitive, and emotional functions. The drTMS treatment with H5 coil included a sequential 1 Hz primary motor cortex stimulation contralateral to the more-affected body side and a bilateral 10 Hz stimulation of the prefrontal cortex. Overall, drTMS could be safely administered to patients with different PSs and medical refractory symptoms, but large variation was apparent in the rate and severity ratings of the reported adverse event/adverse device effect. The treatment significantly decreased the subjective main symptom severity. This effect was more pronounced in older patients with PD. Furthermore, analysis showed an improvement in depression, but no effect could be established in terms of cognitive performance. drTMS can be safely administered to patients with PS and medical refractory symptoms and can decrease the subjective motor symptom severity and depression.
Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. [2023]Studies using repetitive transcranial magnetic stimulation (rTMS) in healthy individuals and those with neuropsychiatric diseases have rapidly increased since the 1990s, due to the potential of rTMS to modulate the cortical excitability in the brain depending on the stimulation parameters; therefore, the safety considerations for rTMS use are expected to become more important. Wassermann published the first safety guidelines for rTMS from the consensus conference held in 1996, and Rossi and colleague then published the second safety guidelines from the multidisciplinary consensus meeting held in Siena, Italy in 2008, on behalf of the International Federation of Clinical Neurophysiology. More than 10 years after the second guidelines, the updated third safety guidelines were recently published in 2021. The general safety guidelines for conventional rTMS have not substantially changed. Because the most frequently used rTMS protocol is conventional (low- and high-frequency) rTMS in research and clinical settings, we focus on reviewing safety issues when applying conventional rTMS with a focal cortical stimulation coil. The following issues will be covered: 1) possible adverse events induced by rTMS; 2) checklists to screen for any precautions and risks before rTMS; 3) safety considerations for dosing conventional rTMS; and 4) safety considerations for using rTMS in stroke and traumatic brain injury.
Mechanisms of 1 Hz Inhibitory and 5 Hz Excitatory Repetitive Transcranial Magnetic Stimulations in Parkinson's Disease: A Functional Magnetic Resonance Imaging Study. [2023]Background: Parkinson's disease (PD) is a progressive disorder with alterations in cortical functional activity. Transcranial magnetic stimulation is known to incur motor benefits in PD by inducing motor activity through cortical connectivity, although the mechanisms are unclear. Objective: The effects of repetitive transcranial magnetic stimulation (rTMS) (at three cortical sites) on functional and structural plasticity were studied in PD to understand inhibitory or excitatory rTMS-induced motor improvement. Methodology: The study was a single blind, randomized, sham-controlled type involving three groups. Three thousand rTMS pulses of frequency 1 Hz were given at primary motor area (in 13 patients of Group A) or premotor area (in Group B, n = 18) and a frequency 5 Hz at supplementary motor area in Group C (n = 19). Clinical rating scores (Unified Parkinson's Disease Rating Scale [UPDRS], Parkinson's Disease Questionaire-39 [PDQ-39]) and motor dexterity were assessed at baseline, after sham and real rTMS sessions. Visuospatial functional magnetic resonance imaging task along with T1-weighted scans (at three Tesla) were used to evaluate the motor execution and planning post rTMS intervention. Results: Improvements (p < 0.05) in UPDRS II, III, Mobility, and activities of daily living of PDQ-39, Purdue Pegboard were observed. Increased blood oxygen level-dependent (BOLD) activations (family-wise error [FWE]-corrected P-value [pFWE] <0.01) were observed in motor cortices, parietal association areas, and cerebellum in groups C and decrease in group A and B after real TMS as compared with sham. Conclusions: Repetitive TMS at motor (1 Hz) and supplementary motor (5 Hz) areas resulted in significant clinical benefits by inducing cortical plasticity. Impact statement TMS daily protocols have been commonly employed to modulate cortical connectivity in Parkinson's disease (PD). This study uses functional magnetic resonance imaging to assess rTMS-related effects in PD. Repetitive TMS protocol at higher pulses (3000/session) in primary and supplementary motor cortices administered weekly was clinically effective and safe. The results revealed functional restoration along with cortical plasticity mechanisms of externally generated movement in PD in response to noninvasive brain stimulation.