NeuroRehabilitation + TES for Cognitive Disorders

(PCN Trial)

Overseen By Kayla Rinna, M.S.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Michigan

Disqualifiers: Epilepsy, Sensory impairments, Drug abuse, others

Compensation: Varies

Number of Visits: Unknown

Duration: 4-6 weeks

500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores methods to enhance thinking skills that may decline due to aging or diseases like Alzheimer’s. It tests whether brain training exercises, combined with a mild electrical treatment called transcranial electrical stimulation (TES), can improve memory, attention, and problem-solving skills. Participants may receive either real or sham treatments to determine the most effective approach. Individuals aged 50 or older who have noticed issues with their thinking abilities might be suitable candidates. As an unphased trial, this study provides a unique opportunity to contribute to research that could improve cognitive health for many.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that treatments like transcranial electrical stimulation (TES) are generally safe. No serious side effects have been reported for methods such as transcranial Direct Current Stimulation (tDCS) and transcranial Alternating Current Stimulation (tACS). Some individuals might experience mild skin issues from tDCS, but this is uncommon.

Studies indicate that cognitive interventions can improve daily tasks and thinking skills, particularly in older adults. These interventions are well-tolerated, with most participants experiencing no major problems.

In summary, both TES and cognitive interventions have demonstrated safety and are usually well-tolerated by participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for cognitive disorders because they leverage transcranial electrical stimulation (TES) techniques like tDCS, tACS, and tRNS to potentially enhance brain function. Unlike traditional methods that rely heavily on medication or behavioral therapy, these TES methods use non-invasive electrical currents to stimulate specific brain areas, promising a more direct impact on neural activity. Additionally, the combination of TES with cognitively based interventions could offer a synergistic effect, possibly accelerating cognitive improvements. This dual approach aims to provide a more comprehensive and personalized treatment strategy, addressing the limitations of current standard options.

What evidence suggests that this trial's treatments could be effective for improving cognitive abilities?

Studies have shown that transcranial electrical stimulation (TES), which participants in this trial may receive, can improve thinking skills in some older adults, particularly those with mild memory problems. However, results can vary, and improvements in memory or decision-making are not always noticeable. In contrast, activities focusing on thinking skills, such as cognitive rehabilitation, offer another treatment option in this trial. These activities often help people manage daily tasks better and slow mental decline. Research suggests they can enhance language skills and memory. This trial will also explore combining TES with cognitive rehabilitation, which might amplify these benefits, though results can differ for each person. ^{6 7 8 9 10}

Who Is on the Research Team?

Benjamin M Hampstead, Ph.D.

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

This trial is for individuals aged 50 or older who have noticed a decline in their cognitive abilities. It's open to those with and without diagnosed cognitive issues. People can't join if they have serious mental illnesses, are pregnant, might become pregnant, have metal/electronic implants in the head, history of substance abuse, or sensory/motor impairments that would limit participation.

Inclusion Criteria

I am 50 years old or older.

Individuals who have reported cognitive dysfunction and cognitively intact participants

Exclusion Criteria

I do not have any sensory or motor impairments that limit my participation.

Being evaluated for TES methodology with metallic or electronic implant, or skull plates or other cranial implants that affect TES

History of serious mental illness (e.g., schizophrenia, axis 2 disorders)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive transcranial electrical stimulation (TES) and/or cognitively based interventions tailored to individual needs, potentially including up to 260 sessions of TES

4-6 weeks

Follow-up

Participants are monitored for cognitive changes and symptomatic changes through neuropsychological testing and questionnaires

6 months

Long-term follow-up

Participants undergo additional assessments such as MRS and fMRI to evaluate long-term changes

Up to 1 year post-treatment

What Are the Treatments Tested in This Trial?

Interventions

• Active tACS
• Active tDCS
• Active tRNS
• Cognitively based intervention
• Sham tACS
• Sham tRNS

Trial Overview

The study tests whether cognitive rehabilitation combined with transcranial electrical stimulation (TES) improves thinking skills like attention and memory. TES involves small electric currents applied to the brain. Participants will receive either active TES (tRNS/tDCS/tACS), sham TES (placebo), or cognitively based interventions.

How Is the Trial Designed?

Group I: Sham TES + Cognitively based intervention Experimental Treatment 4 Interventions

This condition combines sham TES and cognitively based interventions for some or all of the study sessions

Group II: Cognitively based intervention Experimental Treatment 1 Intervention

Participants may receive a cognitively based intervention that targets the particular cognitive and/or functional abilities of interest. This includes methods of cognitive training, cognitive remediation, and cognitive rehabilitation.

Group III: Active and Sham TES Experimental Treatment 6 Interventions

Participants will receive active and sham TES

Group IV: Active TES, Sham TES, Cognitively based interventions Experimental Treatment 7 Interventions

This condition combines active and sham TES with cognitively based interventions using a cross-over design

Group V: Active TES + Cognitively based intervention Experimental Treatment 4 Interventions

This condition combines active TES and cognitively based interventions for some or all of the study sessions

Group VI: Active TES Experimental Treatment 3 Interventions

Participants will receive "real" tES (tDCS, tACS, tRNS) in which they receive up to 4 milliamps (mA) of stimulation per electrode for up to 40 minutes for up to 260 sessions. As this may be a cross-over design, some participants may receive active and sham conditions.

Group VII: Sham TES Placebo Group 3 Interventions

Participants undergoing this condition will have the exact same procedures as the active group, with the exception that they will receive only sham stimulation for up to 260 sessions.

Active tACS is already approved in United States, European Union for the following indications:

Approved in United States as Active tACS for:

• Investigational for cognitive rehabilitation in neurodegenerative diseases and aging-related cognitive decline

Approved in European Union as Active tACS for:

• Investigational for cognitive rehabilitation in neurodegenerative diseases and aging-related cognitive decline

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

Published Research Related to This Trial

A case study of a 29-year-old man with cognitive and emotional issues after a traumatic brain injury showed significant improvements in attention, working memory, and mood after 20 sessions of remotely supervised transcranial direct current stimulation (RS-tDCS) combined with cognitive training.

This study is the first to demonstrate the effectiveness of at-home telerehabilitation using RS-tDCS, suggesting it could be a promising, noninvasive treatment option for cognitive deficits in TBI survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive Telerehabilitation with Transcranial Direct Current Stimulation Improves Cognitive and Emotional Functioning Following a Traumatic Brain Injury: A Case Study. Eilam-Stock, T., George, A., Charvet, LE.[2021]

In a study involving 15 healthy subjects, transcranial random noise stimulation (tRNS) was found to be the most effective method for increasing cortical excitability compared to transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS).

All three stimulation methods (tDCS, tRNS, and tACS) significantly increased motor evoked potentials (MEPs) compared to pre-measurements, but tRNS showed the largest increase, suggesting it could be particularly beneficial for improving motor function in stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Three Non-Invasive Transcranial Electrical Stimulation Methods for Increasing Cortical Excitability. Inukai, Y., Saito, K., Sasaki, R., et al.[2022]

In a study involving 25 participants, it was found that decreasing the intensity of transcranial alternating current stimulation (tACS) from 1.0 mA to 0.4 mA switched the effect from excitation to inhibition of cortical excitability in the primary motor cortex.

The research demonstrated that different intensities of high-frequency transcranial electrical stimulation can selectively control the enhancement or reduction of motor cortex excitability, with 140 Hz tACS producing stronger inhibition than transcranial random noise (tRNS).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Close to threshold transcranial electrical stimulation preferentially activates inhibitory networks before switching to excitation with higher intensities. Moliadze, V., Atalay, D., Antal, A., et al.[2016]

Transcranial alternating current stimulation (tACS) is a promising neurological intervention that can modulate perception, cognition, and consciousness by influencing oscillating neural activity.

tACS has unique advantages, such as the ability to entrain large groups of neurons and provide precise control over effects, making it a valuable tool for studying the neural basis of cognitive functions, but best practices must be followed for effective application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Alternating Current Stimulation (tACS) Mechanisms and Protocols. Tavakoli, AV., Yun, K.[2020]

Transcranial electrical stimulation (TES) can modulate brain activity using low-intensity currents, but the effects observed may not solely be due to the targeted brain region, as peripheral stimulation could also play a significant role.

The review emphasizes the need for careful consideration of TES's biophysical properties and dose-response relationships, suggesting that researchers should control for peripheral effects and be cautious in attributing behavioral changes to specific brain areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can Transcranial Electrical Stimulation Localize Brain Function? Karabanov, AN., Saturnino, GB., Thielscher, A., et al.[2023]

Low intensity transcranial electrical stimulation (TES) is considered safe, with no serious adverse events reported in over 18,000 sessions across various populations, including healthy individuals and patients with neurological or psychiatric conditions.

While moderate adverse events like skin burns from tDCS are rare, mild adverse events such as headaches and fatigue are more common, and the safety profile is consistent across different age groups and vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Antal, A., Alekseichuk, I., Bikson, M., et al.[2023]

Transcranial electrical stimulation (tES) is a non-invasive technique that uses low voltage currents applied to the scalp to influence brain activity, potentially enhancing learning and brain plasticity.

tES is gaining popularity not only in research but also in practical applications such as sports and military training, with numerous clinical trials exploring its effectiveness in treating various neurological disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial electrical stimulation. Bestmann, S., Walsh, V.[2018]

In a case study of a 60-year-old male with mild Alzheimer's disease, transcranial direct current stimulation (tDCS) combined with cognitive tasks helped stabilize global cognitive functioning for about 3 months, while placebo stimulation did not show this effect.

The study suggests that using tDCS as an additional tool alongside cognitive training may slow cognitive decline in Alzheimer's patients, indicating its potential for cognitive rehabilitation, although further research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation and cognitive training in the rehabilitation of Alzheimer disease: A case study. Penolazzi, B., Bergamaschi, S., Pastore, M., et al.[2015]

Transcranial alternating current stimulation (tACS) has been shown to lead to modest to moderate improvements in cognitive function across various domains, including working memory and attention, based on a systematic review of 102 studies involving 2893 participants.

The most significant cognitive improvements were observed after tACS treatment (offline effects) rather than during the stimulation (online effects), and studies that optimized stimulation based on current flow models yielded better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A meta-analysis suggests that tACS improves cognition in healthy, aging, and psychiatric populations. Grover, S., Fayzullina, R., Bullard, BM., et al.[2023]

Transcranial direct current stimulation (tDCS) is a safe and noninvasive method that shows promise in treating cognitive decline associated with Alzheimer's disease and mild cognitive impairment.

The review highlights the need for further large-scale clinical trials to better understand the mechanisms of tDCS and improve its application in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential of Transcranial Direct Current Stimulation in Alzheimer's Disease: Optimizing Trials Toward Clinical Use. Pilloni, G., Charvet, LE., Bikson, M., et al.[2022]

A systematic review of 64 studies involving 2262 participants found that transcranial direct current stimulation (tDCS) has a low dropout rate (6% for active and 7.2% for sham), indicating good acceptability among participants.

Despite the low dropout rates, many studies inadequately reported adverse events (AEs), highlighting a need for improved guidelines to standardize AE reporting in tDCS research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. Aparício, LVM., Guarienti, F., Razza, LB., et al.[2018]

Transcranial Direct Current Stimulation (tDCS) has been shown to be safe, with no reports of Serious Adverse Effects or irreversible injuries across over 33,200 sessions involving more than 1,000 subjects, including vulnerable populations.

Safety assessments indicate that the current densities used in conventional tDCS (≤4 milliamperes) are significantly lower than those that could potentially cause brain injury, suggesting that tDCS protocols are well within safe limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Bikson, M., Grossman, P., Thomas, C., et al.[2022]

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Investigating Different Frequencies of Transcranial ...

This study will investigate the effects of applying different transcranial electrical stimulation (tES) waveforms to find the optimal stimulation when paired ...