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

240 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will test the effects of different doses of a form of non-invasive brain stimulation for the treatment of individuals with mild cognitive impairment (MCI) and dementia of the Alzheimer's Type (DAT).

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 data supports the effectiveness of the treatment HD-tDCS for Alzheimer's Disease?

Research suggests that transcranial direct current stimulation (tDCS), a non-invasive brain stimulation method, shows promise in improving cognitive function and memory in Alzheimer's patients. Studies indicate that tDCS is safe and may help slow down cognitive decline in Alzheimer's disease. ^{1 2 3 4 5}

Is brain stimulation for Alzheimer's disease 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. However, some studies suggest it could potentially cause harm, so caution is advised. ^{3 6 7 8 9}

How is HD-tDCS treatment different from other Alzheimer's treatments?

HD-tDCS (High Definition Transcranial Direct Current Stimulation) is unique because it is a non-invasive brain stimulation method that specifically targets brain areas with more precision than traditional methods, potentially improving memory and cognitive function in Alzheimer's patients without the side effects associated with drugs. ^{1 2 4 10 11}

Research Team

Benjamin Hampstead, PhD

Principal Investigator

Associate Professor

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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]

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) 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 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]

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]

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]

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) 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]

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]

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

Safety, Tolerability, Blinding Efficacy and Behavioural Effects of a Novel MRI-Compatible, High-Definition tDCS Set-Up. [2022]

3. 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]

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

Transcranial direct current stimulation improves recognition memory in Alzheimer disease. [2022]

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

Transcranial Direct Current Stimulation Improves Cognitive Function in Mild to Moderate Alzheimer Disease: A Meta-Analysis. [2020]

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: Evidence Based Update 2016. [2022]

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 in healthy participants. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Action mechanisms of transcranial direct current stimulation in Alzheimer's disease and memory loss. [2021]

11. Netherlands 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. [2020]