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

Trial Summary

What is the purpose of this trial?

As individuals grow older, a number of factors can reduce our cognitive (or thinking) abilities such as "normal" aging, neurodegenerative diseases, and cardiovascular disease. This study will evaluate whether cognitive rehabilitation and transcranial electrical stimulation (TES) can improve cognitive abilities. Cognitive rehabilitation refers to methods that are used to improve tasks people have trouble doing in everyday life. Transcranial electrical stimulation uses small amounts of electricity to try to alter brain functioning. These approaches may help improve cognitive abilities like attention, learning, memory, finding words, and problem solving as well as everyday functioning. The goal of this study is to identify how to best use these methods, either alone or in combination.

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.

What data supports the effectiveness of the treatment NeuroRehabilitation + TES for Cognitive Disorders?

Research shows that transcranial alternating current stimulation (tACS) can modestly to moderately improve cognitive functions like memory and attention in various populations, including older adults and those with psychiatric conditions. Additionally, transcranial random noise stimulation (tRNS) has been found to significantly increase brain activity, suggesting potential benefits for cognitive rehabilitation. ^{1 2 3 4 5}

Is transcranial electrical stimulation (TES) safe for humans?

Transcranial electrical stimulation (TES), including methods like tDCS, tACS, and tRNS, is generally considered safe for humans. Over 18,000 sessions have been conducted without serious adverse events, though mild effects like headaches or skin sensations can occur. Safety is established for low-intensity TES, and no serious injuries have been reported in over 33,200 sessions. ^{1 4 6 7 8}

How is the NeuroRehabilitation + TES treatment different from other treatments for cognitive disorders?

The NeuroRehabilitation + TES treatment is unique because it combines various forms of transcranial electrical stimulation (TES) like tACS, tDCS, and tRNS with cognitive rehabilitation, aiming to enhance brain function and cognitive recovery. This approach is non-invasive, uses low-intensity electrical currents to modulate brain activity, and has shown promise in improving cognitive outcomes in conditions like traumatic brain injury and Alzheimer's disease. ^{3 9 10 11 12}

Research Team

Benjamin M Hampstead, Ph.D.

Principal Investigator

University of Michigan

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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) 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]

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 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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison of Three Non-Invasive Transcranial Electrical Stimulation Methods for Increasing Cortical Excitability. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

A meta-analysis suggests that tACS improves cognition in healthy, aging, and psychiatric populations. [2023]

3. United States 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. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Close to threshold transcranial electrical stimulation preferentially activates inhibitory networks before switching to excitation with higher intensities. [2016]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Transcranial Alternating Current Stimulation (tACS) Mechanisms and Protocols. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Can Transcranial Electrical Stimulation Localize Brain Function? [2023]

10. England pubmed.ncbi.nlm.nih.gov

Transcranial electrical stimulation. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation and cognitive training in the rehabilitation of Alzheimer disease: A case study. [2015]

12. Korea (South) pubmed.ncbi.nlm.nih.gov

Potential of Transcranial Direct Current Stimulation in Alzheimer's Disease: Optimizing Trials Toward Clinical Use. [2022]