Trial Outcomes & Findings for The Revitalize Study in Older Adults at Risk for Alzheimer's Disease (NCT NCT04018092)
NCT ID: NCT04018092
Last Updated: 2025-10-09
Results Overview
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.
Recruitment status
ACTIVE_NOT_RECRUITING
Study phase
PHASE2
Target enrollment
168 participants
Primary outcome timeframe
Baseline; Week 12
Results posted on
2025-10-09
Participant Flow
Study enrollment began August 12, 2020 and ended in 2024, across the University of Florida and University of Arizona sites.
No participants were randomized until they met inclusion-exclusion criteria and completed baseline assessments. A total of 345 participants were screened. Of these, 141 failed to meet inclusion criteria and 28 chose not to continue. The remaining 176 underwent baseline evaluation; of these 8 were excluded due to not wanting to continue (N=5) or due to MRI issues (N=3). This resulted in 168 participants who were randomized to active or sham groups.
Participant milestones
| Measure |
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 once weekly for 10 weeks and b) 44 home sessions of intranasal stimulation. For home sessions, participants use a standalone intranasal device on weekdays when not in the lab.
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 Vielight units.
|
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.
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
|
|---|---|---|
|
Overall Study
STARTED
|
84
|
84
|
|
Overall Study
COMPLETED
|
82
|
82
|
|
Overall Study
NOT COMPLETED
|
2
|
2
|
Reasons for withdrawal
| Measure |
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 once weekly for 10 weeks and b) 44 home sessions of intranasal stimulation. For home sessions, participants use a standalone intranasal device on weekdays when not in the lab.
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 Vielight units.
|
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.
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
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
Baseline Characteristics
The Revitalize Study in Older Adults at Risk for Alzheimer's Disease
Baseline characteristics by cohort
| Measure |
Active NIR-PBM
n=84 Participants
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 once weekly for 10 weeks and b) 44 home sessions of intranasal stimulation. For home sessions, participants use a standalone intranasal device on weekdays when not in the lab.
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 Vielight units.
|
Sham NIR-PBM
n=84 Participants
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.
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
|
Total
n=168 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
71 years
STANDARD_DEVIATION 4.3 • n=93 Participants
|
71 years
STANDARD_DEVIATION 5.2 • n=4 Participants
|
71 years
STANDARD_DEVIATION 4.78 • n=27 Participants
|
|
Sex: Female, Male
Female
|
50 Participants
n=93 Participants
|
52 Participants
n=4 Participants
|
102 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
34 Participants
n=93 Participants
|
32 Participants
n=4 Participants
|
66 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
9 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
16 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
75 Participants
n=93 Participants
|
77 Participants
n=4 Participants
|
152 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
84 participants
n=93 Participants
|
84 participants
n=4 Participants
|
168 participants
n=27 Participants
|
|
Education
|
17 years
STANDARD_DEVIATION 2.3 • n=93 Participants
|
16 years
STANDARD_DEVIATION 2.2 • n=4 Participants
|
16.28 years
STANDARD_DEVIATION 2.24 • n=27 Participants
|
|
Montreal Cognitive Assesment
|
27 units on a scale
STANDARD_DEVIATION 2.2 • n=93 Participants
|
27 units on a scale
STANDARD_DEVIATION 2.0 • n=4 Participants
|
27 units on a scale
STANDARD_DEVIATION 2.14 • n=27 Participants
|
|
Cognitive Complaints Index- Memory Scale
|
24 units on a scale
STANDARD_DEVIATION 6.4 • n=93 Participants
|
23 units on a scale
STANDARD_DEVIATION 6.3 • n=4 Participants
|
23.4 units on a scale
STANDARD_DEVIATION 6.33 • n=27 Participants
|
|
Beck Depression Inventory-II
|
6.4 units on a scale
STANDARD_DEVIATION 5 • n=93 Participants
|
5.4 units on a scale
STANDARD_DEVIATION 4.7 • n=4 Participants
|
5.9 units on a scale
STANDARD_DEVIATION 4.87 • n=27 Participants
|
PRIMARY outcome
Timeframe: Baseline; Week 12Population: Participants included older adults with subjective cognitive complaints and a first degree relative with Alzheimer's disease. A total of 168 were randomized to active (N-84) and sham groups (N=84). The difference in N between those analyzed and enrolled relates to 4 individuals dropping out during the intervention (2 from active and 2 from sham) and 1 additional participant in the ACTIVE group who refused to complete the ARENA task.
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.
Outcome measures
| Measure |
Sham NIR-PBM
n=82 Participants
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.
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
|
Active NIR-PBM
n=81 Participants
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 once weekly for 10 weeks and b) 44 home sessions of intranasal stimulation. For home sessions, participants use a standalone intranasal device on weekdays when not in the lab.
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 Vielight units.
|
|---|---|---|
|
Change in Active Group ARENA Composite Score Compared to Sham Group ARENA Composite Score
|
0.099 units on a scale
Standard Deviation 0.9
|
0.16 units on a scale
Standard Deviation 0.87
|
SECONDARY outcome
Timeframe: Baseline; Week 12Population: Participants included 144 cognitively unimpaired healthy older individuals with a family history of AD dementia and were randomized to the active or sham intervention groups. MRI scans from 24 participants were excluded from the analyses due to scan quality control issues.
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.
Outcome measures
| Measure |
Sham NIR-PBM
n=72 Participants
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.
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
|
Active NIR-PBM
n=72 Participants
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 once weekly for 10 weeks and b) 44 home sessions of intranasal stimulation. For home sessions, participants use a standalone intranasal device on weekdays when not in the lab.
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 Vielight units.
|
|---|---|---|
|
Change in Active Group Network Segregation Compared to Sham Group
Default Mode Network (DMN)
|
-0.025 units on a scale
Standard Deviation 0.42
|
0.117 units on a scale
Standard Deviation 0.42
|
|
Change in Active Group Network Segregation Compared to Sham Group
Frontoparietal Control Network (FPCN)
|
0.044 units on a scale
Standard Deviation 0.26
|
0.090 units on a scale
Standard Deviation 0.26
|
Adverse Events
Active NIR-PBM
Serious events: 6 serious events
Other events: 15 other events
Deaths: 1 deaths
Sham NIR-PBM
Serious events: 5 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Active NIR-PBM
n=84 participants at risk
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.
|
Sham NIR-PBM
n=84 participants at risk
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.
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
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
pneumonia
|
1.2%
1/84 • Number of events 1 • From enrollment until 3 months post intervention (approximately 6 months total).
|
1.2%
1/84 • Number of events 1 • From enrollment until 3 months post intervention (approximately 6 months total).
|
|
Cardiac disorders
chest pain
|
1.2%
1/84 • Number of events 1 • From enrollment until 3 months post intervention (approximately 6 months total).
|
0.00%
0/84 • From enrollment until 3 months post intervention (approximately 6 months total).
|
|
Infections and infestations
osteomyelitis
|
1.2%
1/84 • Number of events 1 • From enrollment until 3 months post intervention (approximately 6 months total).
|
0.00%
0/84 • From enrollment until 3 months post intervention (approximately 6 months total).
|
|
General disorders
dizziness and vomiting
|
1.2%
1/84 • Number of events 1 • From enrollment until 3 months post intervention (approximately 6 months total).
|
0.00%
0/84 • From enrollment until 3 months post intervention (approximately 6 months total).
|
|
Gastrointestinal disorders
abdominal pain
|
1.2%
1/84 • Number of events 1 • From enrollment until 3 months post intervention (approximately 6 months total).
|
0.00%
0/84 • From enrollment until 3 months post intervention (approximately 6 months total).
|
|
Cardiac disorders
atrial fibrillation
|
1.2%
1/84 • Number of events 1 • From enrollment until 3 months post intervention (approximately 6 months total).
|
0.00%
0/84 • From enrollment until 3 months post intervention (approximately 6 months total).
|
|
Eye disorders
lacrimal irritation
|
1.2%
1/84 • Number of events 1 • From enrollment until 3 months post intervention (approximately 6 months total).
|
0.00%
0/84 • From enrollment until 3 months post intervention (approximately 6 months total).
|
|
Musculoskeletal and connective tissue disorders
hip and back pain
|
0.00%
0/84 • From enrollment until 3 months post intervention (approximately 6 months total).
|
1.2%
1/84 • Number of events 2 • From enrollment until 3 months post intervention (approximately 6 months total).
|
|
Gastrointestinal disorders
appendicitis
|
0.00%
0/84 • From enrollment until 3 months post intervention (approximately 6 months total).
|
1.2%
1/84 • Number of events 1 • From enrollment until 3 months post intervention (approximately 6 months total).
|
|
Vascular disorders
pulmonary embolism
|
0.00%
0/84 • From enrollment until 3 months post intervention (approximately 6 months total).
|
1.2%
1/84 • Number of events 2 • From enrollment until 3 months post intervention (approximately 6 months total).
|
|
General disorders
fainting
|
0.00%
0/84 • From enrollment until 3 months post intervention (approximately 6 months total).
|
1.2%
1/84 • Number of events 1 • From enrollment until 3 months post intervention (approximately 6 months total).
|
|
Gastrointestinal disorders
umbilical hernia
|
0.00%
0/84 • From enrollment until 3 months post intervention (approximately 6 months total).
|
1.2%
1/84 • Number of events 1 • From enrollment until 3 months post intervention (approximately 6 months total).
|
Other adverse events
| Measure |
Active NIR-PBM
n=84 participants at risk
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.
|
Sham NIR-PBM
n=84 participants at risk
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.
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
|
|---|---|---|
|
General disorders
headache
|
11.9%
10/84 • Number of events 12 • From enrollment until 3 months post intervention (approximately 6 months total).
|
7.1%
6/84 • Number of events 8 • From enrollment until 3 months post intervention (approximately 6 months total).
|
|
Skin and subcutaneous tissue disorders
skin cancer
|
6.0%
5/84 • Number of events 5 • From enrollment until 3 months post intervention (approximately 6 months total).
|
3.6%
3/84 • Number of events 3 • From enrollment until 3 months post intervention (approximately 6 months total).
|
Additional Information
Dr. Dawn Bowers
University of Florida - Norman Fixel Brain Institute
Phone: 3522220100
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place