Brain Stimulation for Alzheimer's Disease

(STIM Trial)

Overseen By Eileen A Robinson, RN-BC

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Michigan

Disqualifiers: Neurological, Psychiatric, Sensory, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5-30 sessions

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new non-invasive brain stimulation treatment called HD-tDCS (High Definition Transcranial Direct Current Stimulation) for individuals with mild cognitive impairment (MCI) or Alzheimer's-related dementia. Researchers aim to determine how different doses of this treatment might improve memory and thinking skills. Participants may receive a placebo (inactive treatment) or one of three different doses of the actual treatment. Those with MCI or Alzheimer's dementia who are stable on their medications and do not have metallic implants in the upper body can consider joining.

As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could lead to new treatment options.

Will I have to stop taking my current medications?

The trial requires that you have been stable on your current medications for at least 4 weeks before joining, so you should not stop taking them.

What prior data suggests that this brain stimulation technique is safe for individuals with mild cognitive impairment and dementia of the Alzheimer's Type?

Research has shown that HD-tDCS, a type of brain stimulation, is generally safe and easy to tolerate. Past studies reported no serious side effects. Most participants experienced little to no sensation, or only mild ones, during the sessions. This indicates that HD-tDCS is a comfortable and safe option, even at higher levels up to 3 mA. These findings support its use in trials for individuals with mild memory problems and Alzheimer's-related dementia. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about HD-tDCS (high-definition transcranial direct current stimulation) for Alzheimer's disease because it offers a non-invasive approach that could enhance brain function by delivering mild electrical currents directly to specific brain regions. Unlike current Alzheimer's treatments, which primarily focus on managing symptoms with medications like cholinesterase inhibitors and memantine, HD-tDCS aims to directly modulate brain activity, potentially improving cognitive functions. The different dosage levels being explored (1 mA, 2 mA, and 3 mA) allow researchers to identify the optimal stimulation strength for maximizing benefits while minimizing side effects. This novel method stands out for its potential to provide a targeted, drug-free intervention that directly interacts with neural pathways.

What evidence suggests that HD-tDCS could be effective for Alzheimer's disease?

Research has shown that high-definition transcranial direct current stimulation (HD-tDCS) might improve memory in people with Alzheimer's disease. Some studies have found that HD-tDCS can significantly enhance delayed memory, which is the ability to remember things after some time has passed. One study reported noticeable improvements in thinking skills when HD-tDCS targeted the medial prefrontal cortex, a brain region involved in memory and decision-making. However, not all studies have demonstrated clear benefits; some trials found no significant differences in memory and thinking skills between those who received the treatment and those who received a sham treatment (placebo). Despite these mixed results, findings suggest that HD-tDCS has potential for improving memory in people with Alzheimer's. Participants in this trial will receive either a sham stimulation or one of various dosage levels of HD-tDCS to further investigate its effects. ^{4 6 7 8 9}

Who Is on the Research Team?

Benjamin Hampstead, PhD

Principal Investigator

Associate Professor

Are You a Good Fit for This Trial?

This trial is for individuals with mild cognitive impairment or dementia of the Alzheimer's type who can have an MRI and don't have metal/electronic implants in their upper body/head. They must be stable on current medications for at least 4 weeks.

Inclusion Criteria

My medications have not changed in the last 4 weeks.

I have been diagnosed with Mild Cognitive Impairment or Alzheimer's type dementia.

You can't have any metal or electronic implants in your upper body or head that would interfere with MRI or High Definition transcranial direct current stimulation (HD-tDCS).

Exclusion Criteria

I have a specific neurological condition.

I have severe difficulty with my senses (sight, hearing, touch).

Specific mental health conditions

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive HD-tDCS treatment with varying doses (sham, 1 mA, 2 mA, 3 mA) for 30 minutes per session, for between 5-30 sessions

5-30 sessions

Daily sessions

Follow-up

Participants are monitored for changes in cognitive functioning and brain connectivity post-treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• HD-tDCS
• Sham

Trial Overview

The study tests non-invasive brain stimulation (HD-tDCS) at different doses (1 mA, 2 mA, and 3 mA) versus a sham treatment to see its effects on memory in people with cognitive issues related to Alzheimer's.

How Is the Trial Designed?

Group I: 3 mA Dosage Stimulation Experimental Treatment 1 Intervention

3 milliAmp dose of HD-tDCS treatment for 30 minutes, for between 5-30 sessions.

Group II: 2 mA Dosage Stimulation Experimental Treatment 1 Intervention

2 milliAmp dose of HD-tDCS treatment for 30 minutes, for between 5-30 sessions.

Group III: 1 mA Dosage Stimulation Experimental Treatment 1 Intervention

1 milliAmp dose of HD-tDCS treatment for 30 minutes, for between 5-30 sessions.

Group IV: Sham Stimulation Placebo Group 1 Intervention

Sham (placebo) dose of HD-tDCS treatment for 30 minutes, for between 5-30 sessions.

HD-tDCS is already approved in United States, European Union, Canada for the following indications:

Approved in United States as HD-tDCS for:

• Depression
• Anxiety disorders
• Cognitive enhancement

Approved in European Union as HD-tDCS for:

• Major depressive disorder
• Chronic pain management

Approved in Canada as HD-tDCS for:

• Depression
• Anxiety disorders

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

In a study involving 10 patients with Alzheimer's disease, anodal transcranial direct current stimulation (AtDCS) significantly improved recognition memory performance, while cathodal tDCS (CtDCS) led to a decline in performance.

tDCS is shown to be a safe and inexpensive method that could enhance cognitive function in Alzheimer's patients, suggesting potential for further research on its use alongside other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation improves recognition memory in Alzheimer disease. Ferrucci, R., Mameli, F., Guidi, I., et al.[2022]

Anodal transcranial direct current stimulation (tDCS) significantly improved cognitive performance in healthy elderly individuals by increasing neural activity, as evidenced by enhanced P200 and P300 amplitudes during a working memory task.

Cathodal tDCS also showed potential benefits for Alzheimer's disease patients, increasing P200 amplitude and frontal theta activity, suggesting that tDCS can modulate neural function differently based on the individual's cognitive state.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behavioural and electrophysiological modulations induced by transcranial direct current stimulation in healthy elderly and Alzheimer's disease patients: A pilot study. Cespón, J., Rodella, C., Miniussi, C., et al.[2020]

Transcranial direct current stimulation (tDCS) significantly improved cognitive function in patients with mild to moderate Alzheimer's disease, based on a meta-analysis of seven studies involving 146 patients, with a standardized mean difference of 0.37.

Single sessions of tDCS were effective, particularly when stimulating the temporal cortex, while repeated sessions and lower current densities did not show significant benefits, highlighting the need for careful consideration of treatment parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation Improves Cognitive Function in Mild to Moderate Alzheimer Disease: A Meta-Analysis. Cai, M., Guo, Z., Xing, G., et al.[2020]

The novel high-definition transcranial direct current stimulation (HD-tDCS) setup was found to be safe and well-tolerated, with fewer adverse effects compared to conventional tDCS, based on a study involving 60 healthy participants.

HD-tDCS significantly improved cognitive performance on a visual task, indicating its potential for more effective neural modulation, while also being compatible with simultaneous fMRI without causing significant heating or image quality issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, Blinding Efficacy and Behavioural Effects of a Novel MRI-Compatible, High-Definition tDCS Set-Up. Gbadeyan, O., Steinhauser, M., McMahon, K., 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) 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) shows promise as a non-invasive treatment for Alzheimer's disease (AD) by improving cognitive functions such as working and visual recognition memory, based on its ability to alter neuronal activity and cerebral blood flow.

tDCS may also have beneficial effects on other types of dementia, suggesting its potential as a versatile therapeutic tool, but further large-scale studies are needed to confirm its efficacy and mechanisms in various dementia disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Action mechanisms of transcranial direct current stimulation in Alzheimer's disease and memory loss. Hansen, N.[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) 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) 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]

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]

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