Transcranial Stimulation for Memory Loss

(GWI HDtDCS Trial)

Overseen By Jill Ritter, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The University of Texas at Dallas

Must not be taking: Amphetamines, L-dopa, others

Disqualifiers: Neurological disorders, Drug abuse, others

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

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

Compensation: Varies

Number of Visits: 12

Duration: 2 weeks

120 Participants Needed

Trial Summary

What is the purpose of this trial?

A debilitating and common symptom in Gulf War Illnesses (GWI) is the inability to retrieve words. This affects one's conversations, ability to fluidly exchange information verbally and retrieve information from memory. The investigators have discovered 3 brain regions - the PreSupplementary Motor Area (preSMA), caudate nucleus, and the thalamus - that are essential for word retrieval. They have also detected abnormal EEG signals related to these regions in GWI patients who have problems retrieving words. The investigators have used their model of verbal retrieval to design a noninvasive, nonpharmacological treatment that uses High Definition transcranial Direct Current Stimulation (HD tDCS). Using HD tDCS, they deliver small amounts of electric current to areas of the head to stimulate specific brain regions. The objective is to determine if delivery of HD tDCS over the preSMA will improve performance in GWI veterans with a verbal retrieval deficit. The investigators will administer pre-treatment tests of verbal retrieval measures while recording brain electrical activity. They will then administer 10 sessions of HD tDCS over the preSMA (20 minutes a session) in half the veterans. The other half will go through the same procedures, except the current will not be turned on (called the sham condition). The investigators will then compare performance between the "active" and sham group and assess if the treatment had a significant effect on performing verbal retrieval tasks and if there is a change in the ERP markers to account for how the treatment worked. If the treatment is found to be effective it will be offered to those in the sham group at the study's end. The investigators predict this treatment regimen will lead to positive effects on a person's daily functions, especially improved conversational abilities, with few, if any, side effects. They hope to outline the standard procedures for physicians to perform the treatment by creating a manual on how to apply the treatment in a clinical setting so that it will be quickly available to use in multiple sites if the proposed study demonstrates that it is efficacious. This treatment can be made widely available for Warrior Transition Units, military clinics, and VA medical centers. In addition, if successful, this could potentially lead to development of other targets of stimulation to improve other cognitive deficits in GWI, and help alleviate verbal fluency deficits associated with other disorders.

Will I have to stop taking my current medications?

You may need to stop taking certain medications that interact with the treatment, such as amphetamines, L-dopa, and citalopram, among others. It's important to discuss your current medications with the study team to determine if any changes are necessary.

What data supports the effectiveness of the treatment High Definition Transcranial Direct Current Stimulation (HD-tDCS) for memory loss?

Research shows that transcranial direct current stimulation (tDCS), a similar treatment, can enhance memory and learning in both young and older adults. Studies have found that tDCS can improve immediate memory, learning potential, and working memory, and it has been shown to help with memory recall and consolidation over multiple sessions. ^{1 2 3 4 5}

Is transcranial stimulation safe for humans?

Transcranial direct current stimulation (tDCS), including its high-definition version (HD-tDCS), is generally considered safe and well-tolerated in humans, with no serious adverse effects reported in over 33,200 sessions across various studies. However, some studies suggest that it could potentially cause significant issues, so caution is advised, especially for healthy individuals. ^{1 6 7 8 9}

How is the treatment HD-tDCS different from other treatments for memory loss?

HD-tDCS is unique because it uses weak electric currents delivered through multiple electrodes to target specific brain areas, potentially enhancing memory by modulating brain activity. Unlike traditional treatments, it offers a non-invasive approach that can be tailored to stimulate particular brain regions associated with memory. ^{1 3 10 11 12}

Research Team

John Hart, Jr, MD

Principal Investigator

The University of Texas at Dallas

Eligibility Criteria

This trial is for US Gulf War veterans who served between 1990-1991, are right-handed, and were aged 18-50 during service. Participants must understand English and be able to consent. Excluded are those with neurological disorders, severe TBI, drug abuse history, certain medication use, pacemakers or metal in the head.

Inclusion Criteria

My gender, race, or military rank does not exclude me from this trial.

I am fluent in English.

US military veterans serving during the 1990-1991 GW and were deployed to the theater of operations in Southwest Asia (i.e., Iraq, Kuwait, and Saudi Arabia) who are capable of understanding and signing an informed consent document

Exclusion Criteria

I am not fluent in English.

I have a history of serious brain conditions or injuries.

I don't have a pacemaker, medication pumps, severe heart disease, or non-removable metal near my head.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 10 sessions of HD tDCS or sham over the preSMA region, 20 minutes per session, over a two-week period

2 weeks

10 visits (in-person)

Follow-up

Participants are monitored for changes in verbal retrieval performance and ERP markers at 3 and 6 months post-treatment

6 months

2 visits (in-person)

Treatment Details

Interventions

• High Definition Transcranial Direct Current Stimulation
• Sham High Definition Transcranial Direct Current Stimulation

Trial Overview The study tests High Definition transcranial Direct Current Stimulation (HD tDCS) on brain regions linked to word retrieval in Gulf War Illness patients. It compares active HD tDCS against a sham (inactive) treatment over ten sessions to see if it improves verbal abilities.

Participant Groups

Group I: Active HD tDCS Active Control 1 Intervention

Administer 10 20-minute sessions of 1 mA anodal High Definition Transcranial Direct Current Stimulation to the preSMA region over a two week period.

Group II: Sham HD tDCS Placebo Group 1 Intervention

Administer 10 20-minute sessions of sham High Definition Transcranial Direct Current Stimulation to the preSMA region over a two week period.

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?

The University of Texas at Dallas

Lead Sponsor

Trials

71

Recruited

108,000+

University of Texas Southwestern Medical Center

Collaborator

Trials

1,102

Recruited

1,077,000+

Findings from Research

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]

Transcranial direct current stimulation (tDCS) may influence cognitive functions by inducing long-term potentiation (LTP) and long-term depression (LTD), which are crucial for memory and learning processes.

The review highlights both beneficial and disruptive effects of tDCS on memory and learning tasks in normal subjects, suggesting that its impact can vary depending on the specific application and context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Learning, memory, and transcranial direct current stimulation. Brasil-Neto, JP.[2021]

Transcranial direct current stimulation (tDCS) was found to enhance working memory and learning potential in a study of 31 healthy older adults, with 16 receiving actual stimulation and 15 receiving a sham treatment.

The study demonstrated that tDCS is a safe and non-invasive method for improving cognitive functions in older adults, although it did not show significant effects on immediate memory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancing Immediate Memory, Potential Learning, and Working Memory with Transcranial Direct Current Stimulation in Healthy Older Adults. Satorres, E., Meléndez, JC., Pitarque, A., et al.[2023]

Transcranial direct current stimulation (tDCS) significantly improved face-name associative memory in younger adults, with benefits lasting for 24 hours after stimulation, indicating its potential efficacy for enhancing memory in this age group.

In contrast, older adults did not show any improvement in memory performance with tDCS, suggesting that they may be less responsive to this type of cognitive intervention under the conditions tested.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential Age Effects of Transcranial Direct Current Stimulation on Associative Memory. Leach, RC., McCurdy, MP., Trumbo, MC., et al.[2020]

In a study involving 101 healthy young and older adults, multisession transcranial direct-current stimulation (tDCS) significantly improved memory recall, especially in older adults, with effects lasting up to three months after training.

The benefits of tDCS were most pronounced in individuals with lower baseline learning abilities, indicating its potential to help counteract memory impairments in both healthy individuals and those with cognitive challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multisession transcranial direct current stimulation facilitates verbal learning and memory consolidation in young and older adults. Perceval, G., Martin, AK., Copland, DA., et al.[2021]

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]

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) 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]

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]

A systematic review of 16 studies on anodal high-definition transcranial direct current stimulation (HD-tDCS) found no significant improvement in working memory accuracy or reaction time when stimulating the left prefrontal cortex, suggesting limited efficacy of this technique for enhancing working memory.

The effectiveness of HD-tDCS may be influenced by factors such as the frequency of stimulation (repeated use showed better results) and the research design (within-subjects designs had lower effect sizes), indicating that individual differences and study setup play crucial roles in the outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-definition transcranial direct current stimulation (HD-tDCS) for the enhancement of working memory - A systematic review and meta-analysis of healthy adults. Müller, D., Habel, U., Brodkin, ES., et al.[2023]

Transcranial direct current stimulation (tDCS) applied to the left inferior prefrontal cortex during memory tasks in older adults resulted in decreased performance, particularly increasing false alarms in recognizing face-name pairs.

The study indicates that the effectiveness of tDCS may vary based on the individual's baseline cognitive performance, suggesting that it might not be beneficial for all older adults in improving memory tasks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial stimulation over the left inferior frontal gyrus increases false alarms in an associative memory task in older adults. Leach, RC., McCurdy, MP., Trumbo, MC., et al.[2020]

In a study involving 49 healthy older adults, multiple sessions of anodal transcranial direct current stimulation (atDCS) significantly improved item memory performance compared to sham stimulation.

The improvement in memory was associated with increased brain activity in the prefrontal cortex and anterior cingulate cortex, suggesting that atDCS may enhance memory by inducing beneficial neural changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation Enhances Episodic Memory in Healthy Older Adults by Modulating Retrieval-Specific Activation. Huo, L., Zheng, Z., Huang, J., et al.[2021]

References

1. 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]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Learning, memory, and transcranial direct current stimulation. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Enhancing Immediate Memory, Potential Learning, and Working Memory with Transcranial Direct Current Stimulation in Healthy Older Adults. [2023]

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

Differential Age Effects of Transcranial Direct Current Stimulation on Associative Memory. [2020]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Multisession transcranial direct current stimulation facilitates verbal learning and memory consolidation in young and older adults. [2021]

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

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

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

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

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

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

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

High-definition transcranial direct current stimulation (HD-tDCS) for the enhancement of working memory - A systematic review and meta-analysis of healthy adults. [2023]

11. Spain pubmed.ncbi.nlm.nih.gov

Transcranial stimulation over the left inferior frontal gyrus increases false alarms in an associative memory task in older adults. [2020]

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

Transcranial Direct Current Stimulation Enhances Episodic Memory in Healthy Older Adults by Modulating Retrieval-Specific Activation. [2021]