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

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ClinicalTrials.gov Identifier: NCT03543878
Recruitment Status : Recruiting
First Posted : June 1, 2018
Last Update Posted : November 20, 2018
Sponsor:
Collaborator:
Georgia Institute of Technology
Information provided by (Responsible Party):
James Lah, Emory University

Tracking Information
First Submitted Date  ICMJE May 21, 2018
First Posted Date  ICMJE June 1, 2018
Last Update Posted Date November 20, 2018
Actual Study Start Date  ICMJE November 16, 2018
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 31, 2018)
  • Feasibility: amount of time of device use per day. [ Time Frame: Week 8 ]
    The feasibility of the Flicker intervention will be measured by the amount of time (in minutes) of device use per day.
  • Tolerability: participant report [ Time Frame: Week 8 ]
    Tolerability of the Flicker intervention will be assessed by participant report. Participants will be asked "how would you rate the experience using the device?" and possible responses include "fine", "neutral", or "unpleasant".
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03543878 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Stimulating Neural Activity to Improve Blood Flow and Reduce Amyloid: Path to Clinical Trials
Official Title  ICMJE Stimulating Neural Activity to Improve Blood Flow and Reduce Amyloid: Path to Clinical Trials
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.
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.

Study Type  ICMJE Interventional
Study Phase Not Applicable
Study Design  ICMJE 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
Condition  ICMJE Alzheimer Disease
Intervention  ICMJE Device: Flicker
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 Names:
  • driving gamma
  • GammaSense Stimulation System
Study Arms
  • Experimental: Flicker for 8 Weeks
    Participants will receive the Flicker exposure during the entire 8-week treatment period
    Intervention: Device: Flicker
  • Active Comparator: Flicker for 4 Weeks
    Participants will receive the Flicker exposure during the second four weeks of the 8-week treatment period
    Intervention: Device: Flicker
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 31, 2018)
10
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date December 2019
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.
  • Willing to undergo repeated magnetic resonance imaging (MRI) and positron emission tomography (PET) scans.
  • Agrees to blood collection for apolipoprotein E (ApoE) and biomarker testing.
  • Agrees to lumbar puncture over the course of the study for the collection of cerebrospinal fluid (CSF).

Exclusion Criteria:

  • 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.
  • Presence of clinically significant suicide risk, based on the Investigator's judgment informed by a structured clinician interview. Any suicide attempt within the past 1 year of the screening visit is exclusionary.
  • 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.
  • Current use of warfarin or other blood thinners (exclusionary for lumbar puncture).
  • 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.
Sex/Gender
Sexes Eligible for Study: All
Ages 50 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE
Contact: James Lah, MD, PhD 404-727-3509 jlah@emory.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03543878
Other Study ID Numbers  ICMJE IRB00101694
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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: No
Pediatric Postmarket Surveillance of a Device Product: No
IPD Sharing Statement Not Provided
Responsible Party James Lah, Emory University
Study Sponsor  ICMJE Emory University
Collaborators  ICMJE Georgia Institute of Technology
Investigators  ICMJE
Principal Investigator: James Lah, MD, PhD Emory University
PRS Account Emory University
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP