The Revitalize Study in Older Adults at Risk for Alzheimer's Disease

September 23, 2025 updated by: University of Florida

Revitalizing Cognition in Older Adults at Risk for Alzheimer's Disease With Near-Infrared Photobiomodulation

The goal of this multi-site double blinded randomized sham-controlled Phase II clinical trial is to test a novel, relatively low cost, low risk, and potentially high impact therapeutic intervention in older adults who are at increased risk for Alzheimer's disease. The intervention involves transcranial and intranasal delivery of near infrared (NIR) light via light emitting diodes, aka photobiomodulation (PBM). The overall hypothesis, based on animal and pilot studies, is that exposure to NIR stimulation will have beneficial effects on brain health via influence on mitochondrial function as measured by changes in 31Phosphorous (31P) MRS-based markers of ATP, neural network changes in functional connectivity (rs-fMRI), and improved cognitive performance. To test this hypothesis, 168 older adults with subjective cognitive complaints, and a first-degree family history of Alzheimer's disease will be randomized to sham or real treatment groups. Neuroimaging and cognitive outcome measures will be obtained, before and after a 12-week intervention involving transcranial and intranasal NIR-PBM. The intervention protocol will involve "lab" and "home" sessions, and a 3 month post-intervention follow-up. This trial will determine: 1) whether NIR stimulation, relative to sham, improves performance on memory and executive tasks sensitive to hippocampal and frontal brain function in older adults with increased risk for Alzheimer's disease; 2) whether NIR stimulation, relative to sham, enhances brain function and connectivity measured by changes in MRS phosphorous ATP and resting state functional connectivity; and 3) how differences in demographic, neuroimaging, and Alzheimer-related risk factors influence the brain response to NIR stimulation versus sham in older adults with increased risk for Alzheimer's disease. Results will provide key insights into whether this novel NIR intervention can enhance cognition in older adults with increased risk for Alzheimer's disease and will provide the necessary data for a future Phase III randomized clinical trial.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This multi-site randomized sham-controlled trial proposes to test a novel, non-invasive, low risk and low-cost brain stimulation approach for enhancing cognition and brain health in cognitively normal older adults who are at increased risk for Alzheimer's disease. The intervention involves transcranial and intranasal delivery of near-infrared light (NIR; 808-904 nm) via light emitting diodes placed on the scalp or intranasally using a dosing that resulted in positive effects in our pilot studies. We plan to test the hypothesis that targeted NIR stimulation will have positive effects on brain health via influence on mitochondrial function as measured by changes in Magnetic Resonance Spectroscopy (MRS)-based markers of adenosine triphosphate (ATP), neural network changes as indexed by changes in functional connectivity based on resting state-fMRI (rs-fMRI), and improved cognitive performance. We plan to randomize 168 older adults, ages 65-89 years, to Active or Sham intervention conditions. To be included, participants must have subjective cognitive complaints, based on an index of Subjective Cognitive Impairment (SCI), and a family history of Alzheimer's disease in a first degree relative. Performance on standardized neuropsychological measures must be unimpaired psychometrically. The intervention itself will last for 12 weeks and include lab sessions (16 total) and daily at home sessions. In the lab, both transcranial and intranasal delivery of NIR light will be delivered using Medx and Vielight stimulation technologies, whereas the daily at home sessions will involve intranasal stimulation only. The sham and active conditions are identical in all respects except that sham devices will not deliver NIR stimulation. The primary outcome is an episodic memory measure involving spatial navigation that is linked to hippocampal function, sensitive to mild cognitive impairment (MCI) and Alzheimer's disease, and an analogue to the Morris Water maze. Secondary outcomes include executive function tasks and neuroimaging indicators of ATP function (31-P MRS) and connectivity changes based on resting state-fMRI. Exploratory outcomes include 'traditional' neuropsychological measures that are used clinically, along with measures and indices (e.g., apolipoprotein E [APOE-4] status) that might potentially mediate or moderate study outcome. Assessments will occur at baseline (Month 1), after 12 weeks of intervention (Month 4), and 3-month post intervention (Month 7). Imaging outcomes will be assessed only at baseline and at Month 4. Our primary aim is focused on cognition and will test whether NIR intervention, relative to sham, will produce pre-post improvement on tasks of recent memory (primary outcome) and executive function in older adults who are at increased risk for Alzheimer's disease. Our secondary aim is focused on neuroimaging and will test whether NIR intervention, relative to sham, will increase functional connectivity as indexed by resting state fMRI (secondary outcome) and enhance brain markers of MRS-ATP (secondary outcome). The 3rd aim is exploratory and will evaluate how baseline demographic, genetic, neuroimaging and other factors influence individual differences in cognitive outcome for NIR intervention.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
168

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85721
        • University of Arizona
    • Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida McKnight Brain Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

65 years to 89 years (Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Age 65-89 years, at least 8th grade education, community dwelling
  • Subjective report of cognitive complaints with scores >16 on the Cognitive Change Index (CCI-20)
  • No evidence of dementia or mild cognitive impairment based on cognitive screening (i.e., Montreal Cognitive Assessment (MoCA) score within normal limits for age, education and sex using the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) norms.
  • No psychometric evidence of cognitive impairment based on performance on the Neuropsychological Battery from the NACC Unified Data Set, version 3. Scores on these measures cannot be lower than 5th percentile below normative values based on age, education, and gender.
  • Reading at > 8th grade level based on the reading subtest of the Wide Range Achievement Test- IV.
  • Global Clinic Dementia Rating (CDR) score must be 0
  • Family history of dementia/probable Alzheimer's disease in first degree relative (parents, children, siblings)
  • Willingness to be randomized to Sham or Active Intervention
  • Can devote 12 weeks to the intervention with additional time for pre and post testing
  • Normal functional behavior in terms of daily activities, based on the Functional Activities Scale
  • Able to perform cognitive and emotion measures on a computer
  • In line with recommendations of the Subjective Cognitive Decline (SCD) task force an informant must be available for two reasons: a) to provide information about the participant's complaints using the informant version of the CCI-20, and b) to corroborate normal IADL's on the Functional Activity Questionnaire.

Exclusion Criteria:

  • Sensory loss (vision, hearing) or motor deficits that would preclude participation in the experimental tasks or neuropsychological assessment
  • English as a second language
  • Inability to undergo brain imaging due to claustrophobia or implants such as pacemakers, heart valves, brain aneurysm clips, orthodontics, non-removable body jewelry, or shrapnel containing ferromagnetic metal
  • Previous major strokes or other known significant brain abnormalities or diseases affecting the brain and/or cognition (e.g.,Parkinson disease, multiple sclerosis, seizure disorder, brain surgery, moderate traumatic brain injury (TB)I, Rapid Eye Movement (REM) Behavior Sleep Disorder, untreated sleep apnea, etc.)
  • Unstable and uncontrolled medical conditions (metastatic cancer, HIV, moderate-severe kidney disease, uncontrolled diabetes, uncontrolled hypertension, severe cardiac disease, etc.). No current cancer diagnosis.
  • Current or past history of major psychiatric disturbance including schizophrenia, or active psychosis, bipolar disorder, current major depressive episode, current alcohol or substance abuse or history thereof within the past six months.
  • Use of antipsychotics, sedatives, or other medications with significant anticholinergic properties (due to potential influence on memory)
  • Use of prescribed 'memory enhancing' medications such as Aricept or Namenda
  • Use of photo-sensitive medications such as steroids or retin-A within 15 days of the study intervention.
  • Previous participation in a cognitive training study within the last 6 months or current involvement in another study involving cognitive, physical or other intervention at the time of participation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Sham Comparator: Sham NIR-PBM
Participants randomized to the Sham control group will undergo identical procedures as the Active group. The only difference is that the "sham" NIR devices are modified not to deliver stimulation. Because NIR is invisible, participants are unable to detect whether NIR is being delivered.
Device: Sham NIR-PBM
The MedX sham and Vielight interventions device are identical in all respects to the active device, except that the MedX console and diode clusters were modified to NOT deliver NIR light when turned on. The sham MedX devices were modified to deliver 'warmth', similar to that of the active devices. As with the active condition, a total of six sham interventions were given over a 12-week period, following the identical procedures described in the active condition
Experimental: Active NIR-PBM
This condition involves baseline testing, 12 weeks of Near Infrared-Photobiomodulation (NIR-PBM), and post-intervention testing. Cognitive and neuroimaging outcomes are obtained before and after the intervention. The intervention consists of a) 16 laboratory sessions of NIR-PBM given 3 times/week for 2 weeks and then once weekly for 10 weeks and b) 44 home sessions of stimulation delivered intranasally. During each lab session, NIR light is delivered via placement of six MedX LED superluminous diode clusters over the scalp for a total of 40 minutes. Concurrently, two 810 Vielight intranasal devices are placed in each nostril for 25 min of total dose per nostril. During lab sessions, participants sit in front of a monitor and view nature documentaries (BBC Life series). This is done to standardize behavior during the intervention sessions. For home sessions, participants use a standalone 810 intranasal device only on weekdays when not completing a lab session.
Device: Active NIR-PBM
Near infrared light was delivered to the head using two MedX Rehab Console systems (MedX Health, 1116). Each MedX console included a control unit and 3 superluminous light emitting diode (LED) clusters. Each LED cluster (3MedX MCT502) consisted of 52 near infrared diodes and 9 visible red diodes. The 9 red diodes were deactivated. The energy delivered by each cluster was 1 joule [J]/cm2 in 45 sec at treatment wavelength of 870 nm per each 20 min. The LED cluster has an irradiance of 22.2 mW/cm2, treats an area of 22.48 cm2, with an energy density of 26.64/cm2 per cluster (total energy of 599J/cluster). During each session, the 6 clusters were arrayed on the scalp in 2 configurations, 20 minutes per array. Each configuration targeted 6 transcranial sites, guided by the 10-20 system, for a total of 12 sites during the 40-min session. Total energy delivered was 599J/cluster X 12 sites = 7188J. Intranasal stimulation was delivered using..
Other Names:
  • Photobiomodulation
  • Transcranial Near Infrared Stimulation

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Active Group ARENA Composite Score Compared to Sham Group ARENA Composite Score
Time Frame: Baseline; Week 12
ARENA is a computer-based task of spatial memory-navigation that has been linked to hippocampal function and is a human analogue to the Morris water maze. ARENA consists of 9 learning trials and one final probe trial. On each learning trial, the path length and time to reach the target are recorded. On each probe trial, the percent time spent in the spatial quadrant where the target is located is recorded. The dependent variable is a total composite score consisting of mean z-scores for path length, time to reach the target, and %time in the target quadrant during the probe trial (Total Composite). Expected z-score values range from -3 to +3. A change score is computed by subtracting the baseline Total Composite z-score from the post-intervention Composite z scores. Higher scores mean better outcome.
Baseline; Week 12

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Active Group Network Segregation Compared to Sham Group
Time Frame: Baseline; Week 12
Functional brain network segregation (FBNS), as assessed through functional brain MRI, measures the separation between resting state connectivity networks and is indexed by Fisher Z-transformed mean correlations. FBNS is calculated as follows: Mean Within-network correlation minus Mean Between-network correlation/Mean within-network correlation. The major outcome variable was change in segregation (FBNS) from baseline to post-intervention, which has a range from -1 to +1. Larger scores indicate increased network segregation, reflecting a better outcome.
Baseline; Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Florida

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute on Aging (NIA)
University of Arizona

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Gene Alexander, Ph.D., University of Arizona
  • Principal Investigator: Dawn Bowers, Ph.D, University of Florida
  • Principal Investigator: Steve DeKosky, M.D., University of Florida

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 12, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 7, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 10, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 10, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 12, 2019

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 9, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 23, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB201901780 -N
  • R01AG064587 (U.S. NIH Grant/Contract)
  • F31AG071264 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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