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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called transcranial alternating current stimulation (tACS) to determine its safety and effectiveness for people with frontotemporal dementia (FTD), a condition affecting behavior and language. Participants will receive either the real treatment or a sham over a six-week period to compare results. The trial seeks individuals diagnosed with FTD who are on stable medication related to cognition or behavior.

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

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 prior data suggests that this brain stimulation technique is safe for frontotemporal dementia patients?

Research has shown that transcranial alternating current stimulation (tACS) is generally safe and well-tolerated. In one study, people with mild to moderate Alzheimer's disease found tACS manageable. Another review found that tACS not only improved symptoms but also did not cause major side effects. Additionally, a study with 20 people who had memory issues reported that active tACS improved learning and memory recall compared to a fake treatment, without significant negative effects. While more research is needed, these findings suggest tACS might be a safe option for treating brain conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike standard treatments for frontotemporal dementia, which focus on managing symptoms with medications like antidepressants or antipsychotics, transcranial alternating current stimulation (tACS) offers a completely different approach. tACS is unique because it uses electrical currents to stimulate brain activity, specifically targeting neural networks at a frequency of 40 Hz. Researchers are excited about tACS because it could potentially enhance cognitive function and slow disease progression without the side effects associated with pharmaceuticals. This non-invasive technique represents a promising new frontier in treating frontotemporal dementia.

What evidence suggests that this brain stimulation is effective for frontotemporal dementia?

Research suggests that transcranial alternating current stimulation (tACS) might improve thinking and memory in people with Alzheimer's disease. Some studies have shown short-term benefits in areas like memory and language. Although direct evidence for its effects on frontotemporal dementia (FTD) is limited, tACS is considered safe and might enhance brain activity. In this trial, participants will receive either tACS or a sham tACS as a comparator. Improvements in brain function are believed to relate to better brain connections and increased gamma oscillations. Overall, early findings indicate that tACS could be a promising treatment for FTD, but more research is needed to confirm these effects. ^{1 6 7 8 9}

Who Is on the Research Team?

Emiliano Santarnecchi, PhD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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) 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) 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9869764/

Transcranial alternating current stimulation combined with ... This treatment approach is expected to better improve cognitive function in AD patients, especially in some cognitive domains of particular ...

2. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.962684/full

Transcranial alternating current stimulation combined with ... Most of the current trials reported the short-term efficacy of tACS for AD, but only two trials have patient follow-up data. However, cognitive ...

3. academic.oup.com academic.oup.com/braincomms/article/4/2/fcac050/6555375

Evaluation of the effect of transcranial direct current ... Sanches et al. report no language improvement in frontotemporal dementia after applying transcranial direct current stimulation over ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0197458021003341

Brain network modulation in Alzheimer's and ... In AD, the aDMN protocol showed significant improvement in memory (+7%; delta mean T1-T0: 0.3 ± 0.2, p = 0.002) and language (+23%; delta mean T1-T0: 0.7 ± 0.6, ...

5. alzres.biomedcentral.com alzres.biomedcentral.com/articles/10.1186/s13195-023-01297-4

Home-based transcranial alternating current stimulation (tACS ... We expect that this intervention is safe and feasible and results in the improvement of cognition, entrainment of gamma oscillations, increased ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04425148

Gamma-Induction in FrontoTemporal Dementia Trial The main aim of this study is to investigate the safety, tolerability and efficacy of gamma-tACS in patients with behavioral variant (bv)-FTD and semantic ...

7. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1419243/full

a systematic review of treatment parameters and outcomes Across studies that published results on tACS outcome measures, tACS resulted in enhanced symptoms and/or improvements in overall psychopathology for ...

8. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/10.1002/trc2.12219

Gamma‐induction in frontotemporal dementia (GIFTeD ... In this study, we aim to investigate the safety, tolerability, and efficacy of a novel promising therapeutic intervention for FTD based on 40 Hz ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X23017412

The impact of gamma transcranial alternating current ... Results from twenty patients with MCI/AD showed that active tACS significantly improved auditory verbal learning and long delayed recall scores compared to sham ...