High Frequency Light and Sound Stimulation to Improve Brain Functions in Down Syndrome

Sponsor

Massachusetts Institute of Technology (Other)

Overall Status

Recruiting

CT.gov ID

NCT05196984

Collaborator

(none)

Enrollment

Location

Arms

10.8

Anticipated Duration (Months)

2.8

Patients Per Site Per Month

Study Details

Study Description

Brief 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. 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. For the present study, 20 participants with Down Syndrome and 20 cognitively normal adult controls will be recruited, and the investigators will assess their brain waves with electroencephalogram (EEG) before, during, and after light and sound stimulation for safety, feasibility, and to optimize the stimulation device for use in the DS population.

Condition or Disease	Intervention/Treatment	Phase
Down Syndrome	Device: GENUS device (Active Settings) Device: GENUS device (Sham Settings)	N/A

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. 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) during an acute stimulation session. The investigators will recruit 20 participants diagnosed with Down Syndrome and 20 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). Cognitive and mental health evaluations as well as memory tests will be performed on all participants, before and after exposure to the GENUS device, 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. The investigators will use electroencephalography (EEG) to check how the participant's brain waves respond to the stimulation, and use questionnaires to evaluate for safety and tolerability. 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

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Care Provider)

Primary Purpose:

Supportive Care

Official Title:

Acute Exposure of Individuals With Down Syndrome to Gamma Frequency Stimulation

Actual Study Start Date :

Dec 6, 2021

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

Oct 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Down Syndrome Experimental Experimental arm within Down Syndrome participant group: exposure to active 40Hz stimulation for 30-60 minutes.	Device: GENUS device (Active Settings) 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. Other Names: Gamma Frequency Stimulation Light and Sound Stimulation
Sham Comparator: Down Syndrome Sham Sham arm within the Down Syndrome participant group: exposure to control stimulation for 30-60 minutes.	Device: GENUS device (Sham Settings) 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. Other Names: Gamma Frequency Stimulation Light and Sound Stimulation
Experimental: Cognitively Normal Experimental Experimental arm within the cognitively normal control participant group: exposure to active 40Hz stimulation for 30-60 minutes.	Device: GENUS device (Active Settings) 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. Other Names: Gamma Frequency Stimulation Light and Sound Stimulation
Sham Comparator: Cognitively Normal Sham Sham arm within the cognitively normal control participant group: exposure to control stimulation for 30-60 minutes.	Device: GENUS device (Sham Settings) 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. Other Names: Gamma Frequency Stimulation Light and Sound Stimulation

Outcome Measures

Primary Outcome Measures

Feasibility of gamma frequency stimulation [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 [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.

Other Outcome Measures

Changes in memory and cognitive performance after gamma frequency stimulation [Baseline and immediately after the completion of the stimulation]
Exploratory measure to check if there is any change in cantab cognitive battery test performance between baseline and immediately after the completion of the stimulation. The cantab testing battery involves the Motor Screening Task (MOT), the Paired Associates Learning (PAL), the Reaction Time (RTI), and the Multitasking Test (MTT) to test for multitasking, episodic memory, executive function, and processing speed

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

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.

Exclusion Criteria:

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.
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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts Institute of Technology	Cambridge	Massachusetts	United States	02139

Sponsors and Collaborators

Massachusetts Institute of Technology

Investigators

Principal Investigator: Li-Huei Tsai, PhD, Massachusetts Institute of Technology
Principal Investigator: Diane Chan, MD, PhD, Massachusetts Institute of Technology