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

NCT04018092 | Active Not Recruiting Phase 2 Results DMC FDA Device

• 3 other identifiers: IRB201901780 -NR01AG064587F31AG071264
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Cognitive Aging; Alzheimer Disease, Protection Against

Outcome Measures

Primary Outcomes (1)

• Change in Active Group ARENA Composite Score Compared to Sham Group ARENA Composite Score

  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 Outcomes (1)

• Change in Active Group Network Segregation Compared to Sham Group

  Baseline; Week 12

Study Arms (2)

Active NIR-PBM

EXPERIMENTAL

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

Sham NIR-PBM

SHAM COMPARATOR

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

Interventions

Active NIR-PBM DEVICE

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..

Also known as: Transcranial Near Infrared Stimulation, Photobiomodulation

Active NIR-PBM

Sham NIR-PBM DEVICE

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

Sham NIR-PBM

Eligibility Criteria

• Age: 65 Years - 89 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Florida: lead
• University of Arizona: collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (2)

University of Arizona

Tucson, Arizona, 85721, United States

Location

University of Florida McKnight Brain Institute

Gainesville, Florida, 32610, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Low-Level Light Therapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Laser Therapy; Therapeutics; Phototherapy

Limitations and Caveats

Primary limitation pertained to frequency of stimulation. For future trials, we recommend 3-4 sessions per week throughout the entire 12 weeks.

Results Point of Contact

• Title: Dr. Dawn Bowers
• Organization: University of Florida - Norman Fixel Brain Institute

dawnbowers@phhp.ufl.edu

3522220100

Study Officials

• Dawn Bowers, Ph.D

  University of Florida

  PRINCIPAL INVESTIGATOR

• Steve DeKosky, M.D.

  University of Florida

  PRINCIPAL INVESTIGATOR

• Gene Alexander, Ph.D.

  University of Arizona

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Use of a sham-controlled approach provides stringent experimental control, enabling the investigators to control for placebo/expectations, behavioral activation (engaging in study procedures) and practice effects related to repeated administration of the same cognitive tasks. The MedX and Vielight devices used for delivery of active and sham NIR stimulation are identical in all respects regarding design, warmth and operation, except that no stimulation is delivered by the sham devices. Because NIR light is invisible, participants will not be able to discern if receiving active or sham stimulation. The participants, interventionists, and outcome assessors will be blinded to the participants' intervention status: Active vs Sham. At completion of the study, all participants will receive a Placebo Control Questionnaire that asks questions pertaining to what group the participant had been assigned. This data will be examined to determine the effectiveness of blinding.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, sham-controlled: Participants who meet eligibility criteria will be randomized to the Active or Sham condition. The study biostatistician will randomize participants using a 1:1 allocation scheme with stratification based on age, education, and sex. When a new participant arrives, she/he will be randomized to Active or Sham groups depending on covariate characteristics (age, education, sex) and the cumulative distribution of assignments regarding these variables at that point.

Study Record Dates

• First Submitted: July 10, 2019
• First Posted: July 12, 2019
• Study Start: August 12, 2020
• Primary Completion: August 7, 2024
• Study Completion (Estimated): June 30, 2026
• Last Updated: October 9, 2025
• Results First Posted: October 9, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)