Transcranial Direct Current Stimulation for Mild Cognitive Impairment

(PATH Trial)

Overseen By Hannah Cabrera, MCRC

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: HD-tDCS altering

Disqualifiers: Moderate/severe brain injury, Stroke, Heart attack, Substance use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 11

Duration: 6 weeks

75 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking any current medications known to alter HD-tDCS reactivity.

What data supports the effectiveness of the treatment High Definition Transcranial Direct Current Stimulation for Mild Cognitive Impairment?

Research suggests that transcranial direct current stimulation (tDCS) can help improve cognitive functions in people with mild cognitive impairment (MCI) and Alzheimer's disease. Studies have shown that tDCS, a non-invasive brain stimulation method, may enhance cognitive performance and delay cognitive decline in these conditions. ^{1 2 3 4 5}

Is transcranial direct current stimulation (tDCS) safe for humans?

Transcranial direct current stimulation (tDCS) is generally considered safe and well-tolerated in humans, with no reports of serious adverse effects in over 33,200 sessions across various populations, including potentially vulnerable groups like the elderly. ^{4 6 7 8 9}

How is High Definition Transcranial Direct Current Stimulation (HD-tDCS) different from other treatments for mild cognitive impairment?

HD-tDCS is a non-invasive brain stimulation technique that uses a more focused and precise electrical current compared to standard tDCS, potentially offering better targeting of brain areas involved in cognitive function, which may help improve or maintain cognitive abilities in people with mild cognitive impairment. ^{1 2 3 4 10}

What is the purpose of this trial?

This study will probe if the biological changes in amnestic mild cognitive impairment (aMCI) are related to a history of mild traumatic brain injury (mTBI) using high definition transcranial direct current stimulation (HD-tDCS) and blood-derived biomarker tools. Participants who Do as well as those who Do Not have a history of mTBI will be enrolled in the study.

Eligibility Criteria

This trial is for individuals aged 55 and older with amnestic mild cognitive impairment (aMCI). It's open to all genders and ethnicities, fluent in English. Participants must have a history of mild traumatic brain injury (mTBI) or no such history for the control group. Exclusions include recent mTBI, severe brain injuries, major neurological/cardiovascular conditions, substance use disorders, serious psychiatric issues, sensory impairments affecting testing, or skull/brain implants.

Inclusion Criteria

All races/ethnicities

Fluent in English

I am 55 years old or older.

Exclusion Criteria

Current vision or hearing impairment that interferes with testing

I had a mild brain injury in the last year.

Current substance use disorder

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Initial visit includes a blood draw and a baseline memory evaluation

1 visit

1 visit (in-person)

Treatment

Participants undergo HD-tDCS in three conditions: sham-control, active stimulation to frontal region, and active stimulation to left temporal region, each separated by 14 days

6 weeks

10 visits (in-person)

Follow-up

Participants are monitored for changes in cognitive function and memory after treatment

4 weeks

Treatment Details

Interventions

• High Definition Transcranial Direct Current Stimulation

Trial Overview The study investigates if biological changes in aMCI are linked to past mTBIs using high definition transcranial direct current stimulation (HD-tDCS) alongside blood biomarkers. It includes those with and without an mTBI history to compare results.

Participant Groups

Group I: Active left temporal HD-tDCS Active Control 1 Intervention

Electrodes will be placed in a 4x1 ring configuration over the left temporal region in accordance with the International 10-10 EEG system. Stimulation will consist of a ramp up period in which the electrical current is gradually increased, 30 minutes of stimulation at 2 mA, and a ramp down period during which the electrical current is gradually removed. Stimulation will be applied back-to-back over three consecutive days.

Group II: Active left frontal HD-tDCS Active Control 1 Intervention

Electrodes will be placed in a 4x1 ring configuration over the frontal region in accordance with the International 10-10 EEG system. Stimulation will consist of a ramp up period in which the electrical current is gradually increased, 30 minutes of stimulation at 2 mA, and a ramp down period during which the electrical current is gradually removed. Stimulation will be applied back-to-back over three consecutive days.

Group III: Sham HD=tDCS Placebo Group 1 Intervention

Electrodes will be placed in the same 4x1 ring configuration over the frontal region as the active left frontal condition to ensure a useful control condition. Stimulation will consist of a 30-second ramp up period until reaching 2 mA, followed immediately by a 30-second ramp down, and off for 29 minutes. The same ramp up and down process will be repeated in the final minute of the session to help preserve masking of conditions. Sham stimulation will be applied back-to-back over three consecutive days.

High Definition Transcranial Direct Current Stimulation is already approved in United States, European Union for the following indications:

Approved in United States as HD-tDCS for:

• Investigational for various neurological conditions, including depression, chronic pain, and cognitive enhancement

Approved in European Union as HD-tDCS for:

• Investigational for various neurological conditions, including depression, chronic pain, and cognitive enhancement

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Findings from Research

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]

Anodal transcranial direct current stimulation (tDCS) applied to the left dorsolateral prefrontal cortex significantly improved cognitive tasks related to processing speed, selective attention, and planning in five older adults with mild cognitive impairment (MCI).

The study suggests that combining tDCS with cognitive stimulation programs may enhance cognitive performance in individuals with MCI, but further research is needed to explore long-term effects and practical applications in daily life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Transcranial Direct Current Stimulation on the Cognitive Functions in Older Adults with Mild Cognitive Impairment: A Pilot Study. Cruz Gonzalez, P., Fong, KNK., Brown, T.[2022]

In a study involving 34 patients with mild cognitive impairment (MCI), those receiving 20 days of anodal transcranial direct current stimulation (tDCS) showed significant improvements in cognitive functions, including episodic verbal memory and overall cognitive function, compared to a sham group.

The results suggest that anodal tDCS may enhance cognitive symptoms in MCI patients, indicating its potential as a therapeutic tool, although further research is needed to clarify the underlying mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects on cognition of 20-day anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex in patients affected by mild cognitive impairment: a case-control study. Fileccia, E., Di Stasi, V., Poda, R., et al.[2020]

High-Definition transcranial Direct Current Stimulation (HD-tDCS) at amplitudes up to 4 mA was well tolerated by 292 older adults, with no safety-related adverse events reported and mostly mild sensations experienced during sessions.

The study demonstrated effective blinding for both participants and researchers, indicating that the sham stimulation was convincing, which supports the use of higher amplitudes for potentially greater therapeutic effects in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and blinding of high-definition transcranial direct current stimulation among older adults at intensities of up to 4 mA per electrode. El Jamal, C., Harrie, A., Rahman-Filipiak, A., et al.[2023]

In a study involving 22 participants with mild cognitive impairment (MCI), anodal transcranial direct current stimulation (a-tDCS) combined with cognitive training did not enhance cognitive performance compared to sham stimulation, despite increasing blood flow in the right middle frontal cortex.

Cognitive training alone (SMART) showed significant improvements in executive function and memory in the sham group, but these gains did not last for three months, highlighting the potential of cognitive training in improving cognitive performance in MCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive Training and Transcranial Direct Current Stimulation in Mild Cognitive Impairment: A Randomized Pilot Trial. Das, N., Spence, JS., Aslan, S., et al.[2022]

High Definition transcranial direct current stimulation (HD-tDCS) is safe and well-tolerated in older adults, with no serious adverse events reported during a study involving 101 participants at stimulation intensities of 2 mA and 3 mA.

The study demonstrated effective blinding, as participants could not accurately distinguish between active and sham stimulation, indicating that HD-tDCS can be reliably used in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and blinding of 4x1 high-definition transcranial direct current stimulation (HD-tDCS) at two and three milliamps. Reckow, J., Rahman-Filipiak, A., Garcia, S., et al.[2020]

Transcranial Direct Current Stimulation (tDCS) is generally considered safe, but there are concerns that it could lead to significant negative effects in healthy individuals.

The scientific community needs to be alerted about the potential risks of tDCS, emphasizing the importance of protecting healthy volunteers from possible harm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcranial direct current stimulation in healthy participants. Boccard-Binet, S., Sen, A.[2021]

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]

In a study involving 11 patients with Mild Cognitive Impairment (MCI), transcranial direct current stimulation (tDCS) was found to be safe and well-tolerated, with no significant adverse effects reported during the treatment.

tDCS significantly improved memory recall in patients, with benefits observed immediately after treatment and persisting for at least one month, suggesting its potential as a therapeutic strategy for cognitive deficits in MCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility and tolerability of transcranial direct current stimulation in mild cognitive impairment. Murugaraja, V., Shivakumar, V., Sivakumar, PT., et al.[2022]

References

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

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

2. Netherlands pubmed.ncbi.nlm.nih.gov

The Effects of Transcranial Direct Current Stimulation on the Cognitive Functions in Older Adults with Mild Cognitive Impairment: A Pilot Study. [2022]

3. Italy pubmed.ncbi.nlm.nih.gov

Effects on cognition of 20-day anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex in patients affected by mild cognitive impairment: a case-control study. [2020]

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

Tolerability and blinding of high-definition transcranial direct current stimulation among older adults at intensities of up to 4 mA per electrode. [2023]

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

Cognitive Training and Transcranial Direct Current Stimulation in Mild Cognitive Impairment: A Randomized Pilot Trial. [2022]

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

Tolerability and blinding of 4x1 high-definition transcranial direct current stimulation (HD-tDCS) at two and three milliamps. [2020]

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

Safety of transcranial direct current stimulation in healthy participants. [2021]

8. 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]

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

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

10. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical utility and tolerability of transcranial direct current stimulation in mild cognitive impairment. [2022]