Stimulating Neural Activity to Improve Blood Flow and Reduce Amyloid: Path to Clinical Trials
Condition: Alzheimer Disease
MeSH terms: Alzheimer Disease
Study type: Interventional

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.
    

Detailed description: 
      Alzheimer's Disease (AD) is a looming epidemic, with an urgent need for new therapies to
      delay or prevent symptom onset and progression. There is growing awareness that clinical
      trials must target stage-appropriate pathophysiological mechanisms to effectively develop
      disease-modifying treatments. Advances in AD biomarker research have demonstrated changes in
      amyloid, brain metabolism, and other pathophysiologies prior to the onset of memory loss,
      with some markers possibly changing one or two decades earlier. The brain region responsible
      for spatial navigation and memories of experience, the hippocampus, is one of the areas first
      affected in Alzheimer's disease (AD) and other memory disorders. Prior research has shown how
      coordinated electrical activity across many neurons in the hippocampus represents memories of
      experiences and this coordinated activity fails in animal models of AD. The research also
      showed that stimulating neurons to produce a specific component of this activity, called
      gamma oscillations, reduces AD pathology. The goal of this proposal is to translate this
      discovery that stimulating specific patterns of neural activity is neuroprotective from
      rodents to humans using a non-invasive approach. This research includes preclinical testing
      that will be used to design and justify a multi-site clinical trial to test this approach as
      a treatment for AD, for which there are currently no effective therapies.

      Cognito Therapeutics has licensed the technology from prior animal research to transition
      this work to humans. The company will provide the Flicker devices for conducting this study.
      The device is similar to sunglasses and is both comfortable and easy to use.

      Ten participants with mild cognitive impairment will be randomly assigned to two study arms.
      Although all participants will receive Flicker exposure, half of the participants will
      receive the exposure during the entire intervention period (8 weeks of Flicker) while the
      other half of the participants will receive Flicker exposure only during the second half of
      the intervention period (for 4 weeks of active treatment). During the course of the study,
      participants will undergo venous blood draws and lumbar puncture for biomarker analyses at
      baseline, midpoint and at the end of the intervention.
    

Intervention name(s): Flicker
Intervention type(s): Device
Intervention description(s): 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.
Other intervention name(s): driving gamma; GammaSense Stimulation System
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 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.
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Supportive Care