Brain Stimulation for Frontotemporal Dementia

(GIFTeD Trial)

Recruiting at 1 trial location

Overseen By Sara Romanella

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Must be taking: Acetylcholinesterase inhibitors, Memantine

Must not be taking: Chronic migraine medications

Disqualifiers: Alzheimer's, Stroke, Major depression, others

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

Compensation: Varies

Number of Visits: 42

Duration: 6 weeks

70 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an interventional, sham controlled, double-blind study designed to investigate the safety, tolerability and efficacy of 40 Hz transcranial alternating current stimulation (tACS), a form of noninvasive brain stimulation, delivered for 6 weeks once daily in frontotemporal dementia (FTD) patients. Cognition, gamma EEG activity and brain metabolism via FDG-PET will be measured before and after the tACS intervention.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, your medications will be reviewed by a doctor, and a decision will be made based on your medical history and current treatment.

What data supports the effectiveness of this treatment for frontotemporal dementia?

Research suggests that transcranial alternating current stimulation (tACS) may help restore brain activity patterns in frontotemporal dementia, as it is designed to engage neural activity in a specific frequency. While direct evidence for tACS in frontotemporal dementia is limited, similar non-invasive brain stimulation techniques have shown potential in improving cognitive functions in related conditions. ^{1 2 3 4 5}

Is transcranial alternating current stimulation (tACS) safe for humans?

Transcranial alternating current stimulation (tACS) is generally considered safe for humans, with no serious adverse events reported in over 18,000 sessions. Mild side effects like headaches and skin sensations may occur, but they are usually temporary and not severe. ^{2 6 7 8 9}

How is the treatment tACS different from other treatments for frontotemporal dementia?

tACS (transcranial alternating current stimulation) is unique because it is a non-invasive brain stimulation technique that uses specific frequencies to engage neural activity and potentially restore altered brain patterns in frontotemporal dementia, unlike other treatments that do not target brain oscillations in this way. ^{1 2 3 4 5}

Research Team

Emiliano Santarnecchi, PhD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for adults aged 40-80 with a diagnosis of probable frontotemporal dementia, who have completed at least the 8th grade and do not have intellectual disabilities. Participants must be on stable medications for cognition or behavior for over 30 days and have certain scores on cognitive tests. Exclusions include significant other diseases, psychiatric conditions, brain injuries, metal head implants (except dental), pregnancy, substance abuse within six months, hairstyles that impede electrode contact, and other neurodegenerative disorders.

Inclusion Criteria

I am between 40 and 85 years old.

Minimum of completed 8th grade education

I've been on stable doses of medication for cognition or mood for over 30 days.

Exclusion Criteria

A hair style or head dress that prevents electrode contact with the scalp or would interfere with the stimulation (for example: thick braids, hair weave, afro, wig)

My doctor will review my medications to decide if I can join the trial.

My brain scan shows changes or small strokes that don't affect my thinking or movement.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Baseline assessments including behavioral/cognitive evaluations, blood biomarkers, actigraphy, voice biomarkers, EEG and TMS-EEG, MRI, FDG-PET imaging

1-2 weeks

5-8 visits (in-person)

Treatment

Participants receive 6 weeks of daily tACS or Sham tACS sessions

6 weeks

30 visits (in-person)

Post-intervention Assessment

Post-intervention visits including FDG-PET scans, MRI, cognitive testing, tACS with EEG, blood biomarkers and TMS-EEG

1-2 weeks

5-8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including EEG registration, cognitive testing and behavioral markers

3 months

1 visit (in-person)

Treatment Details

Interventions

• sham tACS
• tACS

Trial Overview The study is testing the safety and effectiveness of transcranial alternating current stimulation (tACS) at a frequency of 40 Hz compared to a sham procedure in improving symptoms of frontotemporal dementia. The noninvasive brain stimulation will be administered daily for six weeks. Cognitive function, gamma EEG activity, and brain metabolism are measured before and after treatment.

Participant Groups

Group I: tACS Experimental Treatment 1 Intervention

40 Hz transcranial alternating current stimulation (tACS), 30 daily (Monday-Friday) 1-hour sessions

Group II: Sham tACS Placebo Group 1 Intervention

Sham transcranial alternating current stimulation (tACS), 30 daily (Monday-Friday) 1-hour sessions

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Beth Israel Deaconess Medical Center

Lead Sponsor

Trials

872

Recruited

12,930,000+

Alzheimer's Drug Discovery Foundation

Collaborator

Trials

22

Recruited

3,100+

Findings from Research

Transcranial direct current stimulation (tDCS) significantly improved picture-naming abilities in individuals with anomic Alzheimer or frontotemporal dementias, with a 40% improvement compared to 19% with sham stimulation, lasting at least 2 weeks after treatment.

The benefits of tDCS not only enhanced trained picture-naming tasks but also showed a small positive effect on untrained items and other cognitive tasks, suggesting a broader impact on cognitive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inferior parietal transcranial direct current stimulation with training improves cognition in anomic Alzheimer's disease and frontotemporal dementia. Roncero, C., Kniefel, H., Service, E., et al.[2022]

This study investigates the safety and efficacy of 40 Hz transcranial alternating current stimulation (tACS) in 50 patients with behavioral variant frontotemporal dementia (bvFTD), aiming to restore impaired brain activity associated with the disorder.

The trial will assess not only the safety and tolerability of tACS but also its effects on cognitive function and brain metabolism through various neuropsychological tests and imaging techniques, with results expected by October 2023.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gamma-induction in frontotemporal dementia (GIFTeD) randomized placebo-controlled trial: Rationale, noninvasive brain stimulation protocol, and study design. Assogna, M., Sprugnoli, G., Press, D., et al.[2022]

In a double-blind, randomized, sham-controlled trial involving 70 participants (55 symptomatic and 15 presymptomatic FTD), transcranial direct current stimulation (tDCS) significantly improved intracortical connectivity and clinical scores compared to sham stimulation.

The 2-week treatment with anodal tDCS over the left prefrontal cortex not only enhanced cognitive function but also restored important brain circuits, suggesting that tDCS could be a promising therapeutic approach for managing frontotemporal dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial stimulation in frontotemporal dementia: A randomized, double-blind, sham-controlled trial. Benussi, A., Dell'Era, V., Cosseddu, M., et al.[2022]

Transcranial direct current stimulation (tDCS) significantly improved picture naming abilities in participants with anomic Alzheimer Disease or Frontotemporal dementia, particularly with the left inferior parietotemporal montage, showing lasting effects even 2 weeks post-stimulation.

The effectiveness of tDCS varied based on the montage used and the participants' specific diagnoses, indicating that personalized approaches may be necessary for optimal outcomes in treating anomia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maximizing the Treatment Benefit of tDCS in Neurodegenerative Anomia. Roncero, C., Service, E., De Caro, M., et al.[2022]

In a study involving 12 patients with the behavioral variant of frontotemporal dementia, a single session of transcranial direct current stimulation (tDCS) did not lead to significant improvements in language performance compared to sham stimulation, indicating limited efficacy of this intervention for language deficits in these patients.

The study highlighted the importance of considering the severity of symptoms and the extent of cortical atrophy when evaluating the potential benefits of tDCS in treating language impairments associated with frontotemporal dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the effect of transcranial direct current stimulation on language impairments in the behavioural variant of frontotemporal dementia. Sanches, C., Amzallag, F., Dubois, B., et al.[2022]

Low intensity transcranial electrical stimulation (TES) is considered safe, with no serious adverse events reported in over 18,000 sessions across various populations, including healthy individuals and patients with neurological or psychiatric conditions.

While moderate adverse events like skin burns from tDCS are rare, mild adverse events such as headaches and fatigue are more common, and the safety profile is consistent across different age groups and vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Antal, A., Alekseichuk, I., Bikson, M., et al.[2023]

Transcranial alternating current stimulation (tACS) shows promise in improving cognitive functioning in older adults, with 7 out of 9 studies on cognitively intact individuals reporting cognitive improvements after stimulation.

However, there is significant variability in study methodologies and outcomes, highlighting the need for standardized protocols and a better understanding of how tACS affects different populations, particularly regarding dosing and physiological effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of tACS Effects on Cognitive Functioning in Older Adults Across the Healthy to Dementia Spectrum. Kraft, JD., Hampstead, BM.[2023]

Transcranial direct current stimulation (tDCS) is generally considered safe, with most adverse effects being mild and temporary; however, some cases of persistent skin lesions and rare instances of mania or hypomania have been reported, particularly in patients with depression.

Transcranial alternating current stimulation (tACS) has fewer reported adverse events, and no persistent effects have been documented, but more research is needed to fully establish its safety compared to tDCS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of tDCS and tACS: A review. Matsumoto, H., Ugawa, Y.[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]

References

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

Inferior parietal transcranial direct current stimulation with training improves cognition in anomic Alzheimer's disease and frontotemporal dementia. [2022]

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

Gamma-induction in frontotemporal dementia (GIFTeD) randomized placebo-controlled trial: Rationale, noninvasive brain stimulation protocol, and study design. [2022]

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

Transcranial stimulation in frontotemporal dementia: A randomized, double-blind, sham-controlled trial. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Maximizing the Treatment Benefit of tDCS in Neurodegenerative Anomia. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Evaluation of the effect of transcranial direct current stimulation on language impairments in the behavioural variant of frontotemporal dementia. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. [2023]

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

A Systematic Review of tACS Effects on Cognitive Functioning in Older Adults Across the Healthy to Dementia Spectrum. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Adverse events of tDCS and tACS: A review. [2020]

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

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