Transcranial Stimulation for Memory Loss

(GWI HDtDCS Trial)

Overseen By Michael Motes, PhD

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called High Definition transcranial Direct Current Stimulation (HD tDCS) to help Gulf War veterans improve word retrieval. Veterans with Gulf War Illness often struggle with this, making conversations and memory recall difficult. The trial uses gentle electrical stimulation on specific brain areas to determine if it can enhance verbal skills. Ideal participants are veterans who served in the Gulf War, speak English, and experience word retrieval issues. The goal is to enhance daily communication abilities with minimal side effects. As an unphased trial, this study offers veterans the chance to contribute to innovative research that could improve communication skills.

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 prior data suggests that this treatment is safe?

Research has shown that High Definition transcranial Direct Current Stimulation (HD tDCS) is generally safe for people. Studies have found that a similar treatment, tDCS, can be safely used for up to 20 days. This treatment applies a weak electrical current to the head to influence brain activity.

Past studies revealed no major differences in thinking skills between those who received HD tDCS and those who received a fake (inactive) treatment. This suggests that the treatment is well-tolerated, with few side effects reported.

Overall, HD tDCS appears to be a safe choice for those considering participation in clinical trials. However, discussing any concerns with the study team is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike traditional treatments for memory loss, which often rely on medications or cognitive therapies, High Definition Transcranial Direct Current Stimulation (HD tDCS) offers a non-invasive and targeted approach. Researchers are excited about HD tDCS because it uses low electrical currents to stimulate specific brain regions, potentially enhancing neural activity and improving memory function. This technique could provide a more direct and immediate effect on brain function compared to the gradual changes seen with medication or therapy, making it a promising option for quicker, more precise interventions.

What evidence suggests that High Definition Transcranial Direct Current Stimulation is effective for improving verbal retrieval in Gulf War Illness?

Research has shown that High Definition transcranial Direct Current Stimulation (HD tDCS), which participants in this trial may receive, might improve thinking skills. It has potential benefits for people with vascular cognitive impairment, possibly aiding memory tasks. However, one small study found that improvements in thinking skills were not significantly different from a fake treatment immediately after therapy. In this trial, some participants will receive Sham HD tDCS as a control. Other studies suggest HD tDCS can help with memory in some groups, such as those with Alzheimer's disease. This treatment uses small electric currents to stimulate specific brain areas, potentially enhancing memory and speaking skills. Although results vary, there is hope it can assist people with Gulf War Illness in finding words and improving conversation skills. ^{1 3 5 6 7}

Who Is on the Research Team?

John Hart, Jr, MD

Principal Investigator

The University of Texas at Dallas

Are You a Good Fit for This Trial?

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

I am fluent in English.

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

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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) 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]

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]

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]

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]

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) 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39863318/

High definition transcranial direct current stimulation as an ... The primary outcome was change in total learning and delayed recall on the Rey Auditory Verbal Learning Test (RAVLT) immediately post-treatment and at 8-weeks.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2274580724006150

High definition transcranial direct current stimulation as an ... In this pilot trial, no statistically significant differences on cognitive outcomes were found between sham and active HD-tDCS immediately post-treatment (p's > ...

3. alzres.biomedcentral.com alzres.biomedcentral.com/articles/10.1186/s13195-025-01677-y

A systematic review and meta-analysis of the impact of ... People with AD showed greater improvements compared to those with MCI or dementia (SMD = 0.91, p = 0.02). However, tDCS did not significantly ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04599764

High Definition Transcranial Direct Current Stimulation (HD ... This program and training model have been demonstrated to be effective and beneficial in patients with vascular cognitive impairment. In the CCT ...

5. brainstimjrnl.com brainstimjrnl.com/article/S1935-861X(22)00236-4/fulltext

A systematic review and meta-analysis of healthy adults This systematic review analyzed the current literature on anodal HD-tDCS for WM enhancement, investigating its effectiveness and the influence of different ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11040101/

Safety and feasibility of optimized transcranial direct current ... Previous research has shown that tDCS can be safely used for 20 days and has significant effects on cognitive function (11, 12). Although there ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0197457224001927

Systematic review and meta-analysis of transcranial ... We conducted a meta-analysis of twenty-two trials involving 1074 adults with mild cognitive impairment and Alzheimer's disease.