Alzheimer DiseaseFLICKERNCT03543878
Stimulating Neural Activity to Improve Blood Flow and Reduce Amyloid: Path to Clinical Trials
A study testing Flicker in people with Alzheimer Disease, run by Emory University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 50 to 90 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- Flicker
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Nov 2018to 10 Feb 2020
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Alzheimer Disease
- Being tested
- Flicker
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FlickerDevice
Also called driving gamma, GammaSense Stimulation System
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.
| Study group | Role | What they receive |
|---|---|---|
| Flicker for 8 Weeks | Experimental | Participants will receive the Flicker exposure during the entire 8-week treatment period Receives: 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 Receives: Device: Flicker |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2018
- Study start16 Nov 2018
- Primary completion10 Feb 2020
- Study completion10 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- Georgia Institute of Technology
- Responsible party
- Principal investigator, James Lah, Emory University
- Investigators
- James Lah, MD, PhD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03543878
- Sponsor's protocol ID
- IRB00101694
- Acronym
- FLICKER
- Status last verified
- Feb 2021
- First submitted
- 21 May 2018
- Last updated
- 2 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Stimulating Neural Activity to Improve Blood Flow and Reduce Amyloid: Path to Clinical Trials
- ClinicalTrials.gov ID
- NCT03543878
- Acronym / sponsor ID
- FLICKER / IRB00101694
- Conditions
- Alzheimer Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- Georgia Institute of Technology
- Study start
- 16 Nov 2018 (actual)
- Primary completion
- 10 Feb 2020 (actual)
- Study completion
- 10 Feb 2020 (actual)
- First posted
- 1 Jun 2018 (actual)
- Results
- Posted 2 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Flicker for 8 Weeks | Experimental | Device: FlickerParticipants will receive the Flicker exposure during the entire 8-week treatment period |
| Flicker for 4 Weeks | Active comparator | Device: FlickerParticipants will receive the Flicker exposure during the second four weeks of the 8-week treatment period |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FlickerAlso: driving gamma, GammaSense Stimulation SystemThe 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. | Device | Flicker for 4 Weeks, Flicker for 8 Weeks |
Primary outcome
Percentage of Adherence to Daily Device Use
Time frame: Week 8
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.
Percentage of Maximum Tolerated Stimulation
Time frame: Baseline
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Lah, MD, PhD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Flicker in people with Alzheimer Disease, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Adherence to Daily Device Use (time frame: Week 8). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2021.