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Daily Light and Sound Stimulation to Improve Brain Functions in Alzheimer's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04055376
Recruitment Status : Active, not recruiting
First Posted : August 13, 2019
Last Update Posted : July 1, 2020
Sponsor:
Information provided by (Responsible Party):
Massachusetts Institute of Technology

Brief Summary:

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.

COVID-19 Amendment: Due to the ongoing suspension of all in-person humans subject research across MIT in response to the COVID-19 pandemic, all enrolled participants who have not completed their 6-month visit will have their visit postponed to 9 months with a follow up at 18 months. Subjects who have completed their 6-month visit will still be instructed to continue and return at Month 12 for an evaluation.

OPTIONAL: If the subject would like to come in for an evaluation between Month 9 and 18, we will invite participants to come on Month 12 to complete cognitive testing and EEG.


Condition or disease Intervention/treatment Phase
Alzheimer Disease Alzheimer Dementia Device: GENUS device (Active Settings) Device: GENUS device (Sham Settings) Not Applicable

Detailed Description:

After screening for eligibility, subjects will be randomized into one of two study groups in a 1:1 ratio. Each subject will use a non-invasive light and sound device, called the GENUS device, at home for 1 hour per day for 6 or 9 months. The GENUS device, which is composed of a panel with light-emitting diode (LED) illumination and speakers for auditory stimulation, delivers light and sound at different frequencies.

Subjects in the first group will use the device with active settings, and subjects in the second group will use the device with sham settings. After 6 or 9 months of the daily usage of the device, all subjects will be given an option to continue the daily usage for additional 6 or 9 months. For these additional 6 or 9 months, the device will be set to active settings for all subjects who choose to remain in the study.

Over the first 6 or 9 months, cognitive, mental health and memory evaluations will be performed at baseline, after 1 month, after 3 months, and after 6 or 9 months of daily usage of the device. Blood draws as well as hearing and vision tests will be performed at baseline and after 6 or 9 months of daily usage of the device. Magnetic resonance imaging (MRI) and electroencephalogram (EEG) will also be performed at baseline, after 3 months, and after 6 or 9 months of daily usage of the device. For subjects who choose to continue the daily usage of the device for additional 6 or 9 months, MRI, EEG as well as cognitive, mental health and memory evaluations will be performed at the end of the 6 or 9 additional months of daily usage. One month after the completion of the daily usage, EEG as well as cognitive, mental health and memory evaluations will be performed (this will be 7 or 10 months after the start of the study for subjects who choose not to continue the daily usage of the device after the initial 6 or 9 months; this will be 13 or 19 months after the start of the study for subjects who choose to continue the daily usage of the device for additional 6 or 9 months after the initial 6 or 9 months).

Participants who complete the study protocol and finish the final study visit at Month 12 or 19 will be offered a long-term extension for a total of 36 months with yearly follow up evaluations.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Subjects will be randomly assigned to one of two study groups. Subjects in the first group will use the GENUS device with active settings for 6 or 9 months, and subjects in the second group will use the GENUS device with sham settings for 6 or 9 months. At the end of the 6 or 9 month period, all subjects will be given an option to continue the usage of the GENUS device for additional 6 or 9 months. For these additional 6 or 9 months, the device will be set to active settings for all subjects who choose to remain in the study. A 36-month compassionate use extension will be offered at the completion of all of the study visits.
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: Chronic Treatment of Alzheimer's Disease With Gamma Frequency Stimulation
Actual Study Start Date : August 14, 2019
Estimated Primary Completion Date : April 30, 2025
Estimated Study Completion Date : April 30, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Daily exposure to active stimulation
Subjects in this arm will receive daily exposure to active stimulation
Device: GENUS device (Active Settings)

Participants in the experimental group will use the GENUS device configured to active settings for 60 minutes daily over 6 or 9 months. After 6 or 9 months, each participant will be given an option to continue the daily usage of the GENUS device configured to active settings for additional 6 or 9 months.

Note: Due to the COVID-19 pandemic, participants who have not yet reached the 6-month mark will have their 6 month visit postponed to 9 months.

Other Names:
  • Gamma frequency stimulation
  • Light and sound stimulation

Sham Comparator: Daily exposure to control stimulation
Subjects in this arm will receive daily exposure to control stimulation
Device: GENUS device (Sham Settings)

Participants in the control group will use the GENUS device configured to sham settings for 60 minutes daily over 6 or 9 months. After 6 or 9 months, each participant will be given an option to continue the daily usage of the GENUS device configured to active settings for additional 6 or 9 months.

Note: Due to the COVID-19 pandemic, participants who have not yet reached the 6-month mark will have their 6 month visit postponed to 9 months.

Other Names:
  • Gamma frequency stimulation
  • Light and sound stimulation




Primary Outcome Measures :
  1. Feasibility of at-home light and sound stimulation: amount of time of device usage per day [ Time Frame: Over 6 or 9 months (or over 12 or 18 months for subjects who choose to continue the daily device usage for 6 or 9 additional months) ]
    Feasibility of daily at-home light and sound stimulation will be assessed by keeping track of the amount of time the GENUS device is used per day. The device will automatically log the start and end times of the device usage. The log data will be collected and assessed at the interim analysis time points (Month 1, Month 3) and later time points (Month 6 or 9 and Month 12 or 18).

  2. Safety of daily at-home light and sound stimulation: questionnaire [ Time Frame: Over 6 or 9 months (or over 12 or 18 months for subjects who choose to continue the daily device usage for 6 or 9 additional months) ]
    Safety of daily at-home light and sound stimulation will be assessed by using a daily questionnaire that asks for any adverse effects of the stimulation. The daily questionnaires will be collected and assessed at the interim analysis time point (Month 1) and later time points (Month 6 or 9 and Month 12 or 18).


Other Outcome Measures:
  1. Change in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) score [ Time Frame: Baseline, Month 1, Month 3, Month 6 , and either Month 7 or Month 12 and Month 13. COVID-19 Amendment:Baseline, Month 1, Month 3, Month 9, and either Month 10 or Month 18 and Month 19. ]
    The Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-cog) is a 11-item neuropsychological test that assesses the severity of cognitive impairment. The items determine the patient's orientation, memory, language, and praxis. Total score of the 11 items ranges from 0 to 70 (lower score indicates lower cognitive impairment).

  2. Change in Mini Mental State Examination (MMSE) score [ Time Frame: Baseline, Month 1, Month 3, Month 6, and either Month 7 or Month 12 and Month 13. COVID-19 Amendment:Baseline, Month 1, Month 3, Month 9, and either Month 10 or Month 18 and Month 19. ]
    The Mini Mental State Examination (MMSE) is an 11-item test that assesses the cognitive aspects of mental function. The items assess orientation, memory, attention, language, and visual construction. Total score of the 11 items ranges from 0 to 30 (lower score indicates greater cognitive impairment).

  3. Change in Montreal Cognitive Assessment (MoCA) Test score [ Time Frame: Baseline, Month 1, Month 3, Month 6, and either Month 7 or Month 12 and Month 13. COVID-19 Amendment:Baseline, Month 1, Month 3, Month 9, and either Month 10 or Month 18 and Month 19. ]
    Montreal Cognitive Assessment (MoCA) Test is a 30-question test that assesses the cognitive aspects of mental function. The questions assess visuospatial/executive function, naming, memory, attention, language, abstraction, delayed recall, and orientation. Total score ranges from 0 to 30 (lower score indicates greater cognitive impairment).

  4. Change in National Alzheimer's Coordinating Center Uniform Data Set Neuropsychological Battery (UDS V3) score [ Time Frame: Baseline and Month 6 (and Month 12 for subjects who choose to continue the daily device usage for 6 additional months). COVID-19 Amendment:Baseline and Month 9 (and Month 18 for subjects who continue the daily device usage for 9 additional months. ]
    The National Alzheimer's Coordinating Center Uniform Data Set Neuropsychological Battery (UDS V3) assesses cognitive performance in dementia and mild cognitive impairment due to Alzheimer's Disease. The battery includes Craft Story 21 Recall (immediate and delayed), Benson Complex Figure Copy (immediate and delayed), Number Span Tests, Category Fluency, Trail Making Test A/B, Multilingual Naming Test (MINT), and the Verbal Fluency: Phonemic Test.

  5. Change in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) [ Time Frame: Baseline, Month 1, Month 3, Month 6, and either Month 7 or Month 12 and Month 13. COVID-19 Amendment:Baseline, Month 1, Month 3, Month 9, and either Month 10 or Month 18 and Month 19. ]
    The Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) evaluates cognitive function and is scored in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The total score of the CDR-SB is obtained by summing each of the domain box scores, with scores ranging from 0 to 18 (higher score indicates greater cognitive impairment).

  6. Change in Functional Assessment Scale (FAS) [ Time Frame: Baseline and Month 6 (and Month 12 for subjects who choose to continue the daily device usage for 6 additional months). COVID-19 Amendment:Baseline and Month 9 (and Month 18 for subjects who continue the daily device usage for 9 additional months. ]
    The National Alzheimer's Coordinating Center Functional Assessment Scale (FAS) is a 10-item questionnaire that assesses whether subjects had a difficulty or needed help with activities of daily living in the past 4 weeks at the time of assessment.

  7. Change in Geriatric Depression Scale (GDS) [ Time Frame: Baseline and Month 6 (and Month 12 for subjects who choose to continue the daily device usage for 6 additional months). COVID-19 Amendment:Baseline and Month 9 (and Month 18 for subjects who continue the daily device usage for 9 additional months. ]
    The Geriatric Depression Scale (GDS): Short Form is a brief, 15-item questionnaire in which participants are asked to respond by answering "yes" or "no" in reference to how they felt over the past week. For each item, the answer indicating depression is given one point. Total score of the 15 items ranges from 0 to 15, with scores 0 - 4 considered normal, depending on age, education, and complaints; 5-8 indicating mild depression; 9-11 indicating moderate depression; and 12-15 indicating severe depression.

  8. Change in Neuropsychiatric Inventory Questionnaire (NPI-Q) [ Time Frame: Baseline and Month 6 (and Month 12 for subjects who choose to continue the daily device usage for 6 additional months). COVID-19 Amendment:Baseline and Month 9 (and Month 18 for subjects who continue the daily device usage for 9 additional months. ]
    The Neuropsychiatric Inventory Questionnaire (NPI-Q) is a 12-item structured interview with a caregiver to assess behavioral disturbances. Each item consists of a screening question and sub-questions that are rated "no" (not present) or "yes" (present). Each item is then rated for severity on a 3-point scale including 1 (mild), 2 (Moderate) and 3 (Severe).

  9. Change in blood biomarkers for Alzheimer's Disease [ Time Frame: Baseline and Month 6. COVID-19 Amendment: Baseline and Month 9. ]
    Change in blood biomarkers for Alzheimer's Disease, as assessed by measuring levels of amyloid, tau, and neurofilament light chain in the subject's blood sample.

  10. Change in gene expression in peripheral white blood cells: ribonucleic acid (RNA) sequencing [ Time Frame: Baseline and Month 6. COVID-19 Amendment: Baseline and Month 9. ]
    Change in gene expression in peripheral white blood cells, as assessed by profiling the transcriptome of peripheral white blood cells via ribonucleic acid (RNA) sequencing. The peripheral white blood cells will be isolated and collected from the subject's blood sample.

  11. Change in electroencephalography (EEG) signals [ Time Frame: Baseline, Month 3, Month 6, and either Month 7 or Month 12 and Month 13. COVID-19 Amendment: Baseline, Month 3, Month 9, and either Month 10 or Month 18 and Month 19. ]
    Change in brain waves in the Delta, Theta, Alpha, Beta, and Gamma frequency bands, as assessed by analyzing the electroencephalography (EEG) signals recorded from the subject.

  12. Change in functional Magnetic Resonance Imaging (fMRI) signals [ Time Frame: Baseline, Month 3, and Month 6 (and Month 12 for subjects who choose to continue the daily device usage for 6 additional months). COVID-19 Amendment:Baseline, Month 3, Month 9 (and Month 18 for subjects who continue the daily device usage for 9 months). ]
    Change in functional connectivity and structure of the brain, as assessed by analyzing the functional Magnetic Resonance Imaging (fMRI) signals recorded from the subject.

  13. Total sleep time: Actigraph activity monitor [ Time Frame: Over 7 months (or over 13 months for subjects continuing the daily device usage for 6 additional months). COVID-19 Amendment: Over 10 months (or over 19 months for subjects continuing the daily device usage for 9 additional months) ]
    Total sleep time, as assessed by analyzing the sleep data reported by an Actigraph activity monitor. The activity monitor will be attached to a wristband and worn by the subject through the study completion. The data from the activity monitor will be collected and assessed at the interim analysis time point (Month 1, Month 3) and later time points (Month 6 and either Month 7 or Month 12 and Month 13). COVID Amendment: Data will be collected once every 3-4 months via mail past Month 3 visit.

  14. Sleep efficiency: Actigraph activity monitor [ Time Frame: Over 7 months (or over 13 months for subjects continuing the daily device usage for 6 additional months). COVID-19 Amendment: Over 10 months (or over 19 months for subjects continuing the daily device usage for 9 additional months) ]
    Sleep efficiency, as assessed by analyzing the sleep data reported by an Actigraph activity monitor. The activity monitor will be attached to a wristband and worn by the subject through the study completion. The data from the activity monitor will be collected and assessed at the interim analysis time points (Month 1, Month 3) and later time points (Month 6 and either Month 7 or Month 12 and Month 13). COVID Amendment: Data will be collected once every 3-4 months via mail past Month 3 visit.

  15. Physical activity level: Actigraph activity monitor [ Time Frame: Over 7 months (or over 13 months for subjects continuing the daily device usage for 6 additional months). COVID-19 Amendment: Over 10 months (or over 19 months for subjects continuing the daily device usage for 9 additional months) ]
    Physical activity level, as assessed by analyzing the activity level data reported by an Actigraph activity monitor. The activity monitor will be attached to a wristband and worn by the subject through the study completion. The data from the activity monitor will be collected and assessed at the interim analysis time point (Month 1, Month 3) and later time points (Month 6 and either Month 7 or Month 12 and Month 13). COVID Amendment: Data will be collected once every 3-4 months via mail past Month 3 visit.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   50 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject is between the ages of 50 - 100.
  • Subject must have mild Alzheimer's disease with a Mini Mental State Exam (MMSE) score of 19 -26.
  • Subject 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.
  • Subjects whose primary residence is within 2 hours of Boston
  • Able to complete the 1st month of at home stimulation at their primary residence; if subjects plan to spend more than 1 week away from their primary residence during the trial, their inclusion must be assessed by the research team.

Exclusion Criteria:

  • Subjects who do not have healthcare.
  • Subjects who are being treated with N-methyl-D-aspartate (NMDA) receptor antagonists (eg. Memantine).
  • Subjects on medications that lower seizure threshold such as wellbutrin, ciprofloxacin, levofloxacin, etc.
  • Subjects with history of seizure or epilepsy within the past 24 months.
  • Subjects with clinically significant suicide risk and/or suicide attempt in the past 12 months.
  • 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 anti-epileptic agent.
  • Subjects who have had a stroke within the past 24 months.
  • Subjects diagnosed with migraine headache.
  • 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 hearing or visual impairment.
  • Subjects who have a life expectancy of less than 24 months.
  • Subjects who are pregnant.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04055376


Locations
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United States, Massachusetts
Massachusetts Institute of Technology
Cambridge, Massachusetts, United States, 02139
Sponsors and Collaborators
Massachusetts Institute of Technology
Investigators
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Principal Investigator: Li-Huei Tsai, PhD Massachusetts Institute of Technology
Principal Investigator: Edward S Boyden, PhD Massachusetts Institute of Technology
Principal Investigator: Emery Brown, MD, PhD Massachusetts Institute of Technology
Principal Investigator: Diane Chan, MD, PhD Massachusetts Institute of Technology
Publications:
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Responsible Party: Massachusetts Institute of Technology
ClinicalTrials.gov Identifier: NCT04055376    
Other Study ID Numbers: 1903763319
First Posted: August 13, 2019    Key Record Dates
Last Update Posted: July 1, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Massachusetts Institute of Technology:
Alzheimer Disease
Cognitive Impairment
Non-invasive Sensory Stimulation
Light and Sound Stimulation
Gamma
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders