Down SyndromeNCT05196984
Gamma Frequency Stimulation in Individuals With Down Syndrome
A study testing GENUS device (Active Settings) in people with Down Syndrome, run by Massachusetts Institute of Technology at 1 site in United States.
Trial summary
Down Syndrome (DS) is characterized by an additional copy of chromosome 21, which also increases risk of Alzheimer's Disease (AD). The investigators' lab found a non-invasive way to remove toxic proteins from the brain in AD mouse models. Remarkably, treated mice also have improved memory on behavioral testing. Read more about this study
- Who is it for?
- Ages 25 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Down Syndrome
- What is being tested?
- GENUS device (Active Settings)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Dec 2021to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subject is between the ages of 25-65
- Subject must have a clinically confirmed diagnosis of Down Syndrome (karyotypes optional). Individuals with mosaic Down syndrome will be excluded.
- Subject or their legal guardian is willing to sign informed consent document.
- If subject is deemed to not have capacity to sign the informed consent, he/she will need a legally authorized representative to provide surrogate consent.
- Subject will be medically stable with consistent medication over the previous 3 months.
Who cannot join
- Subjects has history of a dual diagnosis Down Syndrome and Autism
- Subjects with has history of seizure or epilepsy within the past 24 months.
- Subjects with a new diagnosis of Attention-deficit/hyperactivity disorder (ADHD) (< 6 months) or untreated ADHD
- Active treatment with one or more anti-epileptic agent.
- Subjects who have a known history a stroke within the past 24 months.
- Subjects with a known history of migraine headache.
Show all 13Show fewer
- Subjects on medications that lower seizure threshold such as wellbutrin, ciprofloxacin, levofloxacin, etc.
- Subjects with clinically significant suicide risk and/or suicide attempt in the past 1 year.
- Subjects with behavioral problems such as aggression/agitation/impulsivity that might interfere with their ability to comply with protocol.
- Active treatment with one or more psychiatric agent (e.g. antidepressants, antipsychotics, etc).
- Subjects who have an active implantable medical device including but not limited to implantable cardioverter defibrillator (ICD), deep brain stimulator (DBS), cardiac pacemaker, and/or sacral nerve stimulator.
- Subjects who have profound and uncorrected hearing or visual impairment.
- Subjects who are pregnant (self-report).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Massachusetts Institute of Technology
Cambridge, Massachusetts, 02139
Ana Trisini Lipsanopoulos, BS, 617-258-7723, anat13@mit.edu
Li-Huei Tsai, PhD
About this study
Official title: Acute Exposure of Individuals With Down Syndrome to Gamma Frequency Stimulation
Down Syndrome (DS) is characterized by an additional copy of chromosome 21, which also increases risk of Alzheimer's Disease (AD). The investigators' lab found a non-invasive way to remove toxic proteins from the brain in AD mouse models. Remarkably, treated mice also have improved memory on behavioral testing. The investigators then translated this non-invasive method, which uses light and sound to stimulate the brain, to be used in mild Alzheimer's patients and cognitively normal adults. The investigators have also translated this research into a vibrating speaker device to study tactile vibration to stimulate the brain as well. For the present study, 30 participants with Down Syndrome and 30 cognitively normal adult controls will be recruited, and the investigators will assess their brain waves with electroencephalogram (EEG) during light, sound, and tactile stimulation. The investigators will also test for safety, feasibility, and cognitive performance before and after a 30-60 minute session of light and sound stimulation to optimize the stimulation devices for use in the DS population.
Read the detailed description
The hallmark sign of Down Syndrome (DS) is an additional copy of chromosome 21, which is also a risk factor of Alzheimer's Disease (AD). Given the significantly increased likelihood of developing AD in DS, it is imperative to study the impact of a possible disease modifying therapeutic both in the prevention of progression to dementia as well as for changing the course of memory disorders in this population. Development of a non-invasive medical device that is effective in slowing cognitive impairment is not only revolutionary but also possibly cost- effective.
Information processing in the brain is thought to occur through synchronized neuronal activity in the form of network oscillations. Disruptions of gamma oscillations, particularly in the 30 - 50 Hz range, are reported as a potential early hallmark of Alzheimer's disease. Using a non-invasive light (LED) flickering at 40 Hz, investigators were able to show entrainment of 40 Hz gamma oscillations in the visual cortex of Alzheimer's mouse models, along with microglia activation and a significant reduction in amyloid load. Similar gamma activity disruptions have been observed in mouse models of Down Syndrome.
In initial pilot studies, investigators found that the light and sound device is safe to use in cognitively normal adults and adults with mild AD and that the stimulation at 40Hz can be used to entrain their brain activity. Additionally, investigators have found that a vibrating speaker tactile device is safe to use in cognitively normal adults and can also be used to entrain brain activity. While trials are ongoing in the setting of sporadic Alzheimer's Disease, the purpose of this proposed study is to determine whether gamma entrainment through non-invasive 40Hz sensory stimulation can be observed in participants with Down Syndrome as measured by electroencephalogram (EEG) and an acute stimulation session. The investigators will recruit 30 participants diagnosed with Down Syndrome and 30 cognitively normal participants as a comparison group. Participants will be randomly assigned into one of two study conditions within their participant group: an active condition (40Hz stimulation) and a control condition (sham stimulation) for a 30-60 minute light and sound stimulation session. Cognitive and mental health evaluations as well as memory tests will be performed on all participants, before and after exposure to the GENUS light and sound device for 30-60 minutes, which can deliver light and sound waves at different frequencies. The GENUS device is composed of a panel with light-emitting diode (LED) illumination and speakers for auditory stimulation. In addition to the stimulation session, the investigators will also use electroencephalography (EEG) to check how the participant's brain waves respond to the stimulation, and use questionnaires to evaluate for safety and tolerability. The investigators will also use EEG to check how a subset of the participants (10 total individuals) respond to tactile stimulation using a vibrating speaker device. The tactile stimulation will simply be an additional condition during the EEG for these 10 individuals, but will not impact the stimulation session or study condition assignments, which involve only light and sound. This study will provide critical insight into potential longitudinal studies involving non-invasive 40Hz sensory stimulation in subjects with Down Syndrome as a potential intervention for the development of AD.
- Conditions
- Down Syndrome
- Being tested
- GENUS device (Active Settings), GENUS device (Sham Settings)
- Keywords
- Down Syndrome, Alzheimer Disease, Non-Invasive Sensory Stimulation, Light and Sound Stimulation, Gamma, Tactile Stimulation
- Medical subject headings
- Down Syndrome, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GENUS device (Active Settings)Device
Also called Gamma Frequency Stimulation, Light and Sound Stimulation
Participants in the active condition within the Down Syndrome participant group and the Cognitively Normal Control group will use the GENUS device configured to active 40Hz settings for 30-60 minutes.
GENUS device (Sham Settings)Device
Also called Gamma Frequency Stimulation, Light and Sound Stimulation
Participants in the control condition within the Down Syndrome participant group and the Cognitively Normal Control group will use the GENUS device configured to sham settings for 30-60 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Down Syndrome Experimental | Experimental | Experimental arm within Down Syndrome participant group: exposure to active 40Hz stimulation for 30-60 minutes. Receives: Device: GENUS device (Active Settings) |
| Down Syndrome Sham | Sham comparator | Sham arm within the Down Syndrome participant group: exposure to control stimulation for 30-60 minutes. Receives: Device: GENUS device (Sham Settings) |
| Cognitively Normal Experimental | Experimental | Experimental arm within the cognitively normal control participant group: exposure to active 40Hz stimulation for 30-60 minutes. Receives: Device: GENUS device (Active Settings) |
| Cognitively Normal Sham | Sham comparator | Sham arm within the cognitively normal control participant group: exposure to control stimulation for 30-60 minutes. Receives: Device: GENUS device (Sham Settings) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of gamma frequency stimulation
Feasibility of gamma frequency stimulation in subjects with DS will be assessed by analyzing the EEG data from each subject for a sign of change in gamma frequency waves and determining the percent of subjects who show this change.
Measured: Immediately after the completion of stimulation
Incidence of Stimulation-Related Adverse Events
Tolerability and safety of gamma frequency stimulation will be assessed using questionnaires and measures to rate the subjects' overall experience with the stimulation. These questionnaires will monitor for any adverse effects of the stimulation.
Measured: Immediately after the completion of stimulation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2022
- Study start6 Dec 2021
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Down SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts Institute of Technology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Li-Huei Tsai, PhD, Principal investigator, Massachusetts Institute of Technology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05196984
- Sponsor's protocol ID
- 1908962521
- Status last verified
- Mar 2026
- First submitted
- 5 Jan 2022
- Last updated
- 31 Mar 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Parker SE, Mai CT, Canfield MA, Rickard R, Wang Y, Meyer RE, Anderson P, Mason CA, Collins JS, Kirby RS, Correa A; National Birth Defects Prevention Network. Updated National Birth Prevalence estimates for selected birth defects in the United States, 2004-2006. Birth Defects Res A Clin Mol Teratol. 2010 Dec;88(12):1008-16. doi: 10.1002/bdra.20735. Epub 2010 Sep 28.
PubMed 20878909Pueschel SM. Clinical aspects of Down syndrome from infancy to adulthood. Am J Med Genet Suppl. 1990;7:52-6. doi: 10.1002/ajmg.1320370708.
PubMed 2149974
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Exposure of Individuals With Down Syndrome to Gamma Frequency Stimulation
- ClinicalTrials.gov ID
- NCT05196984
- Acronym / sponsor ID
- 1908962521
- Conditions
- Down Syndrome
- Keywords
- Down Syndrome, Alzheimer Disease, Non-Invasive Sensory Stimulation, Light and Sound Stimulation, Gamma, Tactile Stimulation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Massachusetts Institute of TechnologyUniversity, hospital or other
- Study start
- 6 Dec 2021 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 19 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Down Syndrome (DS) is characterized by an additional copy of chromosome 21, which also increases risk of Alzheimer's Disease (AD). The investigators' lab found a non-invasive way to remove toxic proteins from the brain in AD mouse models. Remarkably, treated mice also have improved memory on behavioral testing. The investigators then translated this non-invasive method, which uses light and sound to stimulate the brain, to be used in mild Alzheimer's patients and cognitively normal adults. The investigators have also translated this research into a vibrating speaker device to study tactile vibration to stimulate the brain as well. For the present study, 30 participants with Down Syndrome and 30 cognitively normal adult controls will be recruited, and the investigators will assess their brain waves with electroencephalogram (EEG) during light, sound, and tactile stimulation. The investigators will also test for safety, feasibility, and cognitive performance before and after a 30-60 minute session of light and sound stimulation to optimize the stimulation devices for use in the DS population.
Detailed description
The hallmark sign of Down Syndrome (DS) is an additional copy of chromosome 21, which is also a risk factor of Alzheimer's Disease (AD). Given the significantly increased likelihood of developing AD in DS, it is imperative to study the impact of a possible disease modifying therapeutic both in the prevention of progression to dementia as well as for changing the course of memory disorders in this population. Development of a non-invasive medical device that is effective in slowing cognitive impairment is not only revolutionary but also possibly cost- effective.
Information processing in the brain is thought to occur through synchronized neuronal activity in the form of network oscillations. Disruptions of gamma oscillations, particularly in the 30 - 50 Hz range, are reported as a potential early hallmark of Alzheimer's disease. Using a non-invasive light (LED) flickering at 40 Hz, investigators were able to show entrainment of 40 Hz gamma oscillations in the visual cortex of Alzheimer's mouse models, along with microglia activation and a significant reduction in amyloid load. Similar gamma activity disruptions have been observed in mouse models of Down Syndrome.
In initial pilot studies, investigators found that the light and sound device is safe to use in cognitively normal adults and adults with mild AD and that the stimulation at 40Hz can be used to entrain their brain activity. Additionally, investigators have found that a vibrating speaker tactile device is safe to use in cognitively normal adults and can also be used to entrain brain activity. While trials are ongoing in the setting of sporadic Alzheimer's Disease, the purpose of this proposed study is to determine whether gamma entrainment through non-invasive 40Hz sensory stimulation can be observed in participants with Down Syndrome as measured by electroencephalogram (EEG) and an acute stimulation session. The investigators will recruit 30 participants diagnosed with Down Syndrome and 30 cognitively normal participants as a comparison group. Participants will be randomly assigned into one of two study conditions within their participant group: an active condition (40Hz stimulation) and a control condition (sham stimulation) for a 30-60 minute light and sound stimulation session. Cognitive and mental health evaluations as well as memory tests will be performed on all participants, before and after exposure to the GENUS light and sound device for 30-60 minutes, which can deliver light and sound waves at different frequencies. The GENUS device is composed of a panel with light-emitting diode (LED) illumination and speakers for auditory stimulation. In addition to the stimulation session, the investigators will also use electroencephalography (EEG) to check how the participant's brain waves respond to the stimulation, and use questionnaires to evaluate for safety and tolerability. The investigators will also use EEG to check how a subset of the participants (10 total individuals) respond to tactile stimulation using a vibrating speaker device. The tactile stimulation will simply be an additional condition during the EEG for these 10 individuals, but will not impact the stimulation session or study condition assignments, which involve only light and sound. This study will provide critical insight into potential longitudinal studies involving non-invasive 40Hz sensory stimulation in subjects with Down Syndrome as a potential intervention for the development of AD.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Down Syndrome Experimental | Experimental | Device: GENUS device (Active Settings)Experimental arm within Down Syndrome participant group: exposure to active 40Hz stimulation for 30-60 minutes. |
| Down Syndrome Sham | Sham comparator | Device: GENUS device (Sham Settings)Sham arm within the Down Syndrome participant group: exposure to control stimulation for 30-60 minutes. |
| Cognitively Normal Experimental | Experimental | Device: GENUS device (Active Settings)Experimental arm within the cognitively normal control participant group: exposure to active 40Hz stimulation for 30-60 minutes. |
| Cognitively Normal Sham | Sham comparator | Device: GENUS device (Sham Settings)Sham arm within the cognitively normal control participant group: exposure to control stimulation for 30-60 minutes. |
Who may qualify
- Ages
- 25 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Subject is between the ages of 25-65
- Subject must have a clinically confirmed diagnosis of Down Syndrome (karyotypes optional). Individuals with mosaic Down syndrome will be excluded.
- Subject or their legal guardian is willing to sign informed consent document.
- If subject is deemed to not have capacity to sign the informed consent, he/she will need a legally authorized representative to provide surrogate consent.
- Subject will be medically stable with consistent medication over the previous 3 months.
Key exclusion criteria (13 listed)
- Subjects has history of a dual diagnosis Down Syndrome and Autism
- Subjects with has history of seizure or epilepsy within the past 24 months.
- Subjects with a new diagnosis of Attention-deficit/hyperactivity disorder (ADHD) (< 6 months) or untreated ADHD
- Active treatment with one or more anti-epileptic agent.
- Subjects who have a known history a stroke within the past 24 months.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GENUS device (Active Settings)Also: Gamma Frequency Stimulation, Light and Sound StimulationParticipants in the active condition within the Down Syndrome participant group and the Cognitively Normal Control group will use the GENUS device configured to active 40Hz settings for 30-60 minutes. | Device | Cognitively Normal Experimental, Down Syndrome Experimental |
| GENUS device (Sham Settings)Also: Gamma Frequency Stimulation, Light and Sound StimulationParticipants in the control condition within the Down Syndrome participant group and the Cognitively Normal Control group will use the GENUS device configured to sham settings for 30-60 minutes. | Device | Cognitively Normal Sham, Down Syndrome Sham |
Primary outcome
Feasibility of gamma frequency stimulation
Time frame: Immediately after the completion of stimulation
Feasibility of gamma frequency stimulation in subjects with DS will be assessed by analyzing the EEG data from each subject for a sign of change in gamma frequency waves and determining the percent of subjects who show this change.
Incidence of Stimulation-Related Adverse Events
Time frame: Immediately after the completion of stimulation
Tolerability and safety of gamma frequency stimulation will be assessed using questionnaires and measures to rate the subjects' overall experience with the stimulation. These questionnaires will monitor for any adverse effects of the stimulation.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2026.
- Background: PubMed 20878909Parker SE, Mai CT, Canfield MA, Rickard R, Wang Y, Meyer RE, Anderson P, Mason CA, Collins JS, Kirby RS, Correa A; National Birth Defects Prevention Network. Updated National Birth Prevalence estimates for selected birth defects in the United States, 2004-2006. Birth Defects Res A Clin Mol Teratol. 2010 Dec;88(12):1008-16. doi: 10.1002/bdra.20735. Epub 2010 Sep 28.
- Background: PubMed 2149974Pueschel SM. Clinical aspects of Down syndrome from infancy to adulthood. Am J Med Genet Suppl. 1990;7:52-6. doi: 10.1002/ajmg.1320370708.
- Individual participant dataSharing planned: No
Related trials for Down Syndrome
Not yet recruiting
Fecal Microbiota Transplantation (FMT) to Slow Biological Aging
Aging, Healthy, Aging and Cognitive Health
Active, not recruitingPhase 3
A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia
B Acute Lymphoblastic Leukemia, B Lymphoblastic Lymphoma
Not yet recruiting
Executive Function Play Opportunities for Children With Down Syndrome
Down Syndrome, Trisomy 21
Not yet recruitingObservational study
Hematological Profile in Children With Numerical Chromosomal Disorders
Down Syndrome, Turner Syndrome
RecruitingObservational study
Natural History of Dysregulation and Aging of the Immune System in People With Trisomy 21 With and Without Thymectomy
Down Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Li-Huei Tsai, PhD principal investigator
Massachusetts Institute of Technology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing GENUS device (Active Settings) in people with Down Syndrome, run by Massachusetts Institute of Technology at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 31 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact gamma wave, BS (6172587723, gamma.wave@mit.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility of gamma frequency stimulation (time frame: Immediately after the completion of stimulation). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05196984, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2026.