Gamma Frequency Stimulation for Down Syndrome

Overseen By MJ Quay, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts Institute of Technology

Must not be taking: Anti-epileptics, Antidepressants, Antipsychotics, others

Disqualifiers: Autism, Seizure, Stroke, Migraine, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore a new method to potentially enhance brain function in people with Down Syndrome, who face a higher risk of Alzheimer's Disease. Researchers are using the GENUS (Gamma Frequency Stimulation) device, which delivers light, sound, and tactile vibrations to stimulate the brain. The goal is to determine if these methods can safely improve memory and cognitive performance. Participants must have a confirmed diagnosis of Down Syndrome and be medically stable with consistent medication for the past three months. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new treatments for cognitive improvement.

Will I have to stop taking my current medications?

The trial requires that participants have been on consistent medication for the previous 3 months, so you should not stop taking your current medications. However, if you are on certain medications like anti-epileptic or psychiatric agents, you may not be eligible to participate.

What prior data suggests that this device is safe for use in humans?

Research has shown that the GENUS device, which uses light and sound to stimulate the brain, is safe for people. In early small studies, both healthy adults and those with mild Alzheimer's Disease tolerated it well. These studies confirmed that participants experienced no safety issues during the light and sound sessions. This suggests the treatment is generally safe to use. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the GENUS device for Down syndrome because it offers a non-invasive approach to potentially improve cognitive function. Unlike current treatments for Down syndrome, which primarily focus on managing symptoms through behavioral interventions and medications, the GENUS device uses 40Hz gamma frequency stimulation. This novel technique aims to directly influence brain activity and enhance cognitive processes. This innovative mechanism of action sets it apart from existing options and provides hope for more targeted cognitive improvements.

What evidence suggests that the GENUS device is effective for Down Syndrome?

Research has shown that 40Hz light and sound can improve brain health in mice with Down syndrome. In these studies, sensory stimulation improved memory and brain connections in the mice. This method has also been tested in people with mild Alzheimer's, showing promising results in boosting brain function. The current trial studies the GENUS device, which uses this type of stimulation, for its potential to help people with Down syndrome by enhancing brain activity and memory. While more research is needed, these early findings suggest this method could support brain health. Participants in this trial will join either an experimental arm receiving active 40Hz stimulation or a sham arm receiving control stimulation. ^{1 2 3 6 7}

Who Is on the Research Team?

Li-Huei Tsai, PhD

Principal Investigator

Massachusetts Institute of Technology

Diane Chan, MD, PhD

Principal Investigator

Massachusetts Institute of Technology

Are You a Good Fit for This Trial?

This trial is for adults aged 25-65 with Down Syndrome, who are medically stable and have not changed medications in the last 3 months. They must be able to give consent or have a guardian do so. Excluded are those with recent strokes, migraines, untreated ADHD, certain medication use (like Wellbutrin), significant psychiatric risks, behavioral issues affecting protocol adherence, active medical implants, severe sensory impairments, pregnancy, autism co-diagnosis or recent seizures.

Inclusion Criteria

I have been diagnosed with Down Syndrome, not the mosaic type.

If I can't consent, someone legally allowed will do it for me.

I am between 25 and 65 years old.

Exclusion Criteria

I have had a stroke in the last 2 years.

I have severe hearing or vision loss that cannot be corrected.

You have a medical device implanted in your body, such as a pacemaker or neurostimulator.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stimulation Session

Participants undergo a 30-60 minute session of light and sound stimulation to assess brain wave entrainment and cognitive performance

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness immediately after stimulation

Immediately after stimulation

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• GENUS device

Trial Overview The study tests a non-invasive GENUS device that uses light and sound to stimulate the brain. It aims to improve cognitive function by removing toxic proteins associated with Alzheimer's Disease risk in people with Down Syndrome. Participants will undergo EEGs during stimulation sessions to measure brain waves and assess safety and cognitive effects.

How Is the Trial Designed?

Group I: Down Syndrome Experimental Experimental Treatment 1 Intervention

Experimental arm within Down Syndrome participant group: exposure to active 40Hz stimulation for 30-60 minutes.

Group II: Cognitively Normal Experimental Experimental Treatment 1 Intervention

Experimental arm within the cognitively normal control participant group: exposure to active 40Hz stimulation for 30-60 minutes.

Group III: Down Syndrome Sham Placebo Group 1 Intervention

Sham arm within the Down Syndrome participant group: exposure to control stimulation for 30-60 minutes.

Group IV: Cognitively Normal Sham Placebo Group 1 Intervention

Sham arm within the cognitively normal control participant group: exposure to control stimulation for 30-60 minutes.

GENUS device is already approved in United States for the following indications:

Approved in United States as 40Hz Light and Sound Therapy for:

• Alzheimer's disease

Who Is Running the Clinical Trial?

Massachusetts Institute of Technology

Lead Sponsor

Trials

104

Recruited

12,810,000+

Published Research Related to This Trial

A collaborative effort by the National Down Syndrome Society and the LuMind IDSC Foundation brought together over 50 experts to identify critical research gaps in Down syndrome (DS) and develop recommendations for future studies.

The recommendations aim to enhance health and quality of life for individuals with DS over the next decade, providing a framework for policymakers and the DS community to create a comprehensive national research strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opportunities, barriers, and recommendations in down syndrome research. Hendrix, JA., Amon, A., Abbeduto, L., et al.[2023]

Gamma Entrainment Using Sensory stimulation (GENUS) shows promise as a non-pharmacological treatment for Alzheimer's disease, with animal studies indicating it can positively affect cognitive decline and reduce amyloid plaques and neurofibrillary tangles.

Although research on GENUS in humans is still in early stages, initial findings suggest it is feasible and warrants further investigation to establish its effectiveness as a disease-modifying intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the use of gamma (multi)sensory stimulation for Alzheimer's disease treatment. Manippa, V., Palmisano, A., Filardi, M., et al.[2023]

A study involving 10 patients with mild cognitive impairment due to Alzheimer's disease demonstrated that daily 1-hour sessions of gamma flicker stimulation (40 Hz) were safe, well-tolerated, and adhered to over 4 to 8 weeks.

Preliminary results indicated that this gamma flicker stimulation may positively influence neural activity and immune factors in the nervous system, suggesting potential benefits for further research in Alzheimer's treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A feasibility trial of gamma sensory flicker for patients with prodromal Alzheimer's disease. He, Q., Colon-Motas, KM., Pybus, AF., et al.[2022]

A study involving 45 children with Down syndrome found that sensory integrative therapy, vestibular stimulation combined with sensory integrative therapy, and neurodevelopmental therapy all improved balance and locomotor skills after 3 months of treatment.

Significant improvements were noted in specific balance and locomotor tests, suggesting that a combination of therapies tailored to individual needs is beneficial for rehabilitation in children with Down syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of different therapy approaches in children with Down syndrome. Uyanik, M., Bumin, G., Kayihan, H.[2019]

The Timed Up and Go (TUG) and Timed Up and Down Stairs (TUDS) tests showed high test-retest reliability in a study of 12 children with Down syndrome, indicating they can be consistently used to assess mobility.

The minimal detectable change (MDC) was found to be 1.26 seconds for the TUG and 12.52 seconds for the TUDS, suggesting that only the TUG test is clinically useful for tracking meaningful changes in mobility over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minimal Detectable Change for TUG and TUDS Tests for Children With Down Syndrome. Martin, K., Natarus, M., Martin, J., et al.[2018]

Chronic exposure to 40 Hz auditory and visual stimulation significantly reduced α-synuclein deposition in neurons of the motor cortex in Parkinson's disease mice, suggesting a potential method to modify disease pathology.

The 40 Hz stimulation improved neuromuscular strength, spatial working memory, and reduced depressive-like behaviors in Parkinson's disease mice, indicating its therapeutic potential for addressing both motor and non-motor symptoms of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive auditory and visual stimulation attenuates α-Synuclein deposition and improves motor and non-motor symptoms in PD mice. Liu, Y., Liu, H., Lu, Y., et al.[2023]

In a study of 79 children with Down syndrome, significant delays in gross motor functions such as standing and walking were observed, with only 10% of children under 3 years achieving these milestones compared to 95% of those aged 3-6 years.

There is a strong correlation between balance and gross motor function, suggesting that both should be addressed together in physical therapy to improve overall motor development in children with Down syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delays in Motor Development in Children with Down Syndrome. Malak, R., Kostiukow, A., Krawczyk-Wasielewska, A., et al.[2018]

In a study with 20 healthy participants, 40 Hz gamma-frequency violet light (VL) stimulation was found to induce unique changes in EEG activity, particularly increasing alpha-gamma coupling, which may enhance visual processing.

Compared to white light (WL), 40 Hz-VL resulted in lower enhancements in delta and theta bands, suggesting that VL may have a different neuromodulatory effect on brain activity than WL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photobiological Neuromodulation of Resting-State EEG and Steady-State Visual-Evoked Potentials by 40 Hz Violet Light Optical Stimulation in Healthy Individuals. Noda, Y., Takano, M., Hayano, M., et al.[2021]

The study aims to evaluate the effectiveness of combining transcranial direct current stimulation (tDCS) with virtual reality (VR) training to improve functional and sensory skills in children with Down syndrome, using a sample of children aged 6 to 12 years.

Participants will be randomly assigned to either an active tDCS group or a sham tDCS group, undergoing 10 sessions of training, with evaluations conducted before, after, and one month post-intervention to assess improvements in motor and cognitive skills.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain activity and upper limb movement analysis in children with Down syndrome undergoing transcranial direct current stimulation combined with virtual reality training: study protocol for a randomized controlled trial. Lopes, JBP., Miziara, IM., Kahani, D., et al.[2023]

A novel non-invasive therapy that modulates neuronal activity in the gamma frequency band (30-100 Hz) shows promise for treating Alzheimer's disease, particularly through external brain stimulation techniques.

Recent studies, including those using mouse models, suggest that this approach may effectively enhance brain activity related to Alzheimer's, indicating a potential new avenue for treatment beyond traditional pharmacological methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gamma Band Neural Stimulation in Humans and the Promise of a New Modality to Prevent and Treat Alzheimer's Disease. McDermott, B., Porter, E., Hughes, D., et al.[2019]

Citations

1. picower.mit.edu picower.mit.edu/news/down-syndrome-mice-40hz-light-and-sound-improve-cognition-neurogenesis-connectivity

In Down syndrome mice, 40Hz light and sound improve ... In Down syndrome mice, 40Hz light and sound improve cognition, neurogenesis, connectivity. Study provides new evidence that sensory stimulation ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05196984

Gamma Frequency Stimulation in Individuals With Down ... Participants in the active condition within the Down Syndrome participant group and the Cognitively Normal Control group will use the GENUS device configured to ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11952037/

40 Hz multisensory stimulation therapy for cognitive impairment This study explores the impact of a 40 Hz multisensory stimulation treatment on brain function, behavior, and disease progression in animal models

4. news.mit.edu news.mit.edu/2025/evidence-40hz-gamma-stimulation-promotes-brain-health-expanding-0314

Evidence that 40Hz gamma stimulation promotes brain ... Tsai's lab has been studying whether it can help with Down syndrome as well. The open questions may help define the next decade of GENUS ...

5. nature.com nature.com/articles/s41422-023-00920-1

40 Hz light flickering promotes sleep through cortical ... 40 Hz light flickering for 30 min also promoted sleep in children with insomnia by decreasing sleep onset latency, increasing total sleep time, and reducing ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04055376

NCT04055376 | Daily Light and Sound Stimulation to ... In this trial, the safety and effect of daily exposure to light and sound stimulation on people with mild Alzheimer's Disease (AD) will be studied.

7. sciencedaily.com sciencedaily.com/releases/2022/12/221201163449.htm

Small studies of 40Hz sensory stimulation confirm safety, ... "In these clinical studies we were pleased to see that volunteers did not experience any safety issues and used our experimental light and sound ...