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Gamma Frequency Stimulation in Individuals With Down Syndrome

Primary Purpose

Down Syndrome

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
GENUS device (Active Settings)
GENUS device (Sham Settings)
Sponsored by
Massachusetts Institute of Technology
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Down Syndrome focused on measuring Down Syndrome, Alzheimer Disease, Non-Invasive Sensory Stimulation, Light and Sound Stimulation, Gamma, Tactile Stimulation

Eligibility Criteria

25 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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).

Sites / Locations

  • Massachusetts Institute of TechnologyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Sham Comparator

Experimental

Sham Comparator

Arm Label

Down Syndrome Experimental

Down Syndrome Sham

Cognitively Normal Experimental

Cognitively Normal Sham

Arm Description

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

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

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

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

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Full Information

First Posted
January 5, 2022
Last Updated
October 13, 2022
Sponsor
Massachusetts Institute of Technology
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1. Study Identification

Unique Protocol Identification Number
NCT05196984
Brief Title
Gamma Frequency Stimulation in Individuals With Down Syndrome
Official Title
Acute Exposure of Individuals With Down Syndrome to Gamma Frequency Stimulation
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 6, 2021 (Actual)
Primary Completion Date
September 1, 2023 (Anticipated)
Study Completion Date
October 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Massachusetts Institute of Technology

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Product Manufactured in and Exported from the U.S.
Yes

5. 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Down Syndrome
Keywords
Down Syndrome, Alzheimer Disease, Non-Invasive Sensory Stimulation, Light and Sound Stimulation, Gamma, Tactile Stimulation

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Down Syndrome Experimental
Arm Type
Experimental
Arm Description
Experimental arm within Down Syndrome participant group: exposure to active 40Hz stimulation for 30-60 minutes.
Arm Title
Down Syndrome Sham
Arm Type
Sham Comparator
Arm Description
Sham arm within the Down Syndrome participant group: exposure to control stimulation for 30-60 minutes.
Arm Title
Cognitively Normal Experimental
Arm Type
Experimental
Arm Description
Experimental arm within the cognitively normal control participant group: exposure to active 40Hz stimulation for 30-60 minutes.
Arm Title
Cognitively Normal Sham
Arm Type
Sham Comparator
Arm Description
Sham arm within the cognitively normal control participant group: exposure to control stimulation for 30-60 minutes.
Intervention Type
Device
Intervention Name(s)
GENUS device (Active Settings)
Other Intervention Name(s)
Gamma Frequency Stimulation, Light and Sound Stimulation
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
GENUS device (Sham Settings)
Other Intervention Name(s)
Gamma Frequency Stimulation, Light and Sound Stimulation
Intervention Description
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.
Primary Outcome Measure Information:
Title
Feasibility of gamma frequency stimulation
Description
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.
Time Frame
Immediately after the completion of stimulation
Title
Incidence of Stimulation-Related Adverse Events
Description
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.
Time Frame
Immediately after the completion of stimulation
Other Pre-specified Outcome Measures:
Title
Changes in memory and cognitive performance after gamma frequency stimulation
Description
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
Time Frame
Baseline and immediately after the completion of the stimulation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gabrielle C de Weck, BS
Phone
6172587723
Email
gdeweck@mit.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Li-Huei Tsai, PhD
Organizational Affiliation
Massachusetts Institute of Technology
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Diane Chan, MD, PhD
Organizational Affiliation
Massachusetts Institute of Technology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts Institute of Technology
City
Cambridge
State/Province
Massachusetts
ZIP/Postal Code
02139
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gabrielle C de Weck, BS
Phone
617-258-7723
Email
gdeweck@mit.edu
First Name & Middle Initial & Last Name & Degree
Li-Huei Tsai, PhD
First Name & Middle Initial & Last Name & Degree
Diane Chan, MD, PhD
First Name & Middle Initial & Last Name & Degree
Brennan L Jackson, BA
First Name & Middle Initial & Last Name & Degree
Vanesa Fernandez, MD
First Name & Middle Initial & Last Name & Degree
Erin Kitchener, PhD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
20878909
Citation
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.
Results Reference
background
PubMed Identifier
2149974
Citation
Pueschel SM. Clinical aspects of Down syndrome from infancy to adulthood. Am J Med Genet Suppl. 1990;7:52-6. doi: 10.1002/ajmg.1320370708.
Results Reference
background

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Gamma Frequency Stimulation in Individuals With Down Syndrome

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