Stimulating Neural Activity to Improve Blood Flow and Reduce Amyloid: Path to Clinical Trials

NCT03543878 | Completed Results FDA Device

• 1 other identifier: IRB00101694
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Alzheimer's disease is characterized by the accumulation of toxic proteins in the brain. Mechanisms to remove these proteins have been the target of many drug trials. This study is designed to use a device to entrain brain waves to a specific frequency to see if rodent research can be replicated in humans with mild cognitive impairment. Ten participants will be recruited from the Emory Alzheimer's Disease Research Center (ADRC) database and assigned to either treatment for 8 weeks or treatment for 4 weeks. This latter group will serve as the control group (4 weeks no treatment, 4 weeks treatment). It is hypothesized that exposure to the gamma oscillations (Flicker) will clear toxic proteins from the brain and increase cerebral blood flow.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (2)

• Percentage of Adherence to Daily Device Use

  Feasibility of the Flicker intervention is defined as adherence to Flicker exposure, at home, for one hour per day for the duration of the intervention period (4 or 8 weeks). The percentages of completed sessions are presented here.

  Week 8

• Percentage of Maximum Tolerated Stimulation

  Participants rated their tolerance to Flicker stimulation prior to the study intervention, using a 1 - 5 point Likert scale for each of the 10 levels of brightness (visual stimulation) and each of the 10 levels of loudness (auditory stimulation) after 60 seconds of stimulation at each level. A rating of 1 indicated stimulation "can be withstood and comfortable," 3 indicated stimulation is "tolerable, but not necessarily comfortable," and 5 indicated stimulation "cannot be withstood or is uncomfortable." Ratings of 1, 2, and 3 were considered tolerable. After determining tolerance for auditory and visual stimulation separately, participants were exposed to combined visual and auditory levels beginning one level above the participant's highest stimulation that received a rating of 3 or lower. Tolerability of brightness and loudness levels of combined auditory stimulation was assessed for 60 seconds. See Analysis Population Description for more details.

  Baseline

Study Arms (2)

Flicker for 8 Weeks

EXPERIMENTAL

Participants will receive the Flicker exposure during the entire 8-week treatment period

Device: Flicker

Flicker for 4 Weeks

ACTIVE COMPARATOR

Participants will receive the Flicker exposure during the second four weeks of the 8-week treatment period

Device: Flicker

Interventions

Flicker DEVICE

The Flicker intervention is delivered with the GammaSense Stimulation System by Cognito Therapeutics and involves viewing flickering lights at gamma frequency (like a strobe light but faster) to drive gamma oscillations in visual brain areas. The GammaSense Stimulation System is a device consisting of a pair of opaque glasses with a light-emitting diode (LED) illumination on the interior of the glasses. Headphones worn by the user during the stimulation session provide the auditory stimulation. When activated for the treatment session, the device will generate light and sound oscillations at 40 cycles per second (Hz) for 60 minutes. Participants will use the device daily during their active treatment period.

Also known as: driving gamma, GammaSense Stimulation System

Flicker for 4 Weeks; Flicker for 8 Weeks

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have a subjective memory concern as reported by subject, study partner or clinician.
• Meets local criteria for diagnosis of mild cognitive impairment (MCI).
• Montreal Cognitive Assessment (MoCA) score \>15. Exceptions may be made for subjects with less than 8 years of education at the discretion of the PI.
• Clinical Dementia Rating = 0.5. Memory Box score must be at least 0.5.
• General cognition and functional performance sufficiently preserved such that a diagnosis of Alzheimer's Disease (AD) cannot be made by the physician at the time of the screening visit.
• Stable on medications for 4 weeks prior to initiation of study sessions.
• Geriatric Depression Scale (GDS) ≤ than 6.
• Male or female outpatients aged 50-90 (inclusive).
• Able to hear without the use of hearing aids.
• Study partner who lives with the participant and can provide a reliable assessment of the participant's level of function, is available for all clinic visits, and can serve as a supervisor/monitor for the home-based Flicker sessions for the duration of the study.
• Visual and auditory acuity adequate for neuropsychological testing.
• Good general health with no diseases expected to interfere with the study.
• Completed six grades of education or has a good work history (sufficient to exclude mental retardation).
• Able to communicate in English with study personnel.
• Able to understand the nature of the study and provision of written informed consent prior to conduct of any study procedures.

You may not qualify if:

• Any significant neurologic disease other than MCI and suspected incipient AD, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, poorly controlled seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities.
• Screening/baseline MRI scan with evidence of infection, large vessel infarction or other focal structural lesions that could account for the memory deficits. Subjects with multiple lacunes or lacunes in a critical memory structure are excluded.
• Contraindication to MRI due to pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body, or excessive weight.
• Major depression, bipolar disorder as described in Diagnostic and Statistical Manual of Mental Disorders-4 (DSM-IV) within the past 1 year, or history of schizophrenia.
• Psychotic features, agitation or behavioral problems within the last 3 months which could lead to difficulty complying with the protocol.
• History of alcohol or substance abuse or dependence within the past 2 years (DSM-IV criteria).
• Known history of epilepsy or migraines, which may be exacerbated by study intervention.
• History of narrow angle (acute angle) glaucoma.
• Inability to obtain initial CSF sample.
• Current use of Namenda (memantine).
• Current use of medications that lower seizure threshold, including Wellbutrin, Ciprofloxacin, Levofloxacin, Seroquel, Phenergan, and Sumatriptan.
• Current use of anti-psychotic medication.
• CSF profile inconsistent with underlying Alzheimer's Disease pathology.
• Reasonable likelihood for non-compliance with the protocol or any other reason, in the opinion of the investigator, prohibits enrollment of subject into the study.
• Exceptions to these guidelines may be considered on a case-by-case basis at the discretion of the protocol director.

Sponsors & Collaborators

• Emory University: lead
• Georgia Institute of Technology: collaborator

Study Sites (1)

12 Executive Park Drive

Atlanta, Georgia, 30329, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Flicker Fusion

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Ophthalmological; Diagnostic Techniques and Procedures; Diagnosis; Ocular Physiological Phenomena

Results Point of Contact

• Title: Annabelle C. Singer, PhD
• Organization: Georgia Institute of Technology

asinger@gatech.edu

510-501-9659

Study Officials

• James Lah, MD, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Participants will be randomly assigned to one of two study arms. One group will receive the Flicker exposure for 8 weeks while the other group will receive the active exposure for 4 weeks.

Study Record Dates

• First Submitted: May 21, 2018
• First Posted: June 1, 2018
• Study Start: November 16, 2018
• Primary Completion: February 10, 2020
• Study Completion: February 10, 2020
• Last Updated: March 2, 2021
• Results First Posted: March 2, 2021

Record last verified: 2021-02

Locations

US (1)