Phase 2 - Rhythmic Light Therapy for Alzheimer's Disease Patients

Sponsor

Icahn School of Medicine at Mount Sinai (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05016219

Collaborator

(none)

120

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Participants will randomly be placed into one of four groups and experience one of the four following conditions: (1) a placebo light that provides a 40 hertz (Hz) flicker (rhythmic light [RL]); (2) a placebo light with a random flicker (placebo condition for rhythmic light); (3) a light source that will stimulate the circadian system and provides a 40 Hz flicker (RL); or (4) a light source that will stimulate the circadian system and provides a random flicker (placebo condition for rhythmic light). Following a baseline week, participants will experience his/her assigned lighting condition for two hours in the morning for 8 weeks. After a 4-week washout period, a final round of assessments will be obtained. Study assessments (except for the Pittsburgh Sleep Quality Index and Montreal Cognitive Assessment) will be collected at the end of each week, for a total of 8 assessments.

Condition or Disease	Intervention/Treatment	Phase
Mild Cognitive Impairment	Device: Circadian-Effective Light Device: Rhythmic Light Device: Placebo Light Device: Placebo Rhythmic Light	N/A

Detailed Description

The tailored lighting intervention used to promote circadian entrainment will provide high circadian stimulation during the day produced by narrowband blue light peaking at 470 nanometers (nm). A comparison lighting intervention (i.e., placebo lighting), a narrowband red light peaking at 630 nm, will be used as a control. Both the red and the blue light devices will also provide either the 40 hertz (Hz) flicker (RL) or the random flicker (placebo RL). For the random flicker (placebo RL), the duty cycle will be delivered with a random interval determined by a Poisson process with an average interval of 40 hertz (Hz).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Phase 2 - The Use of Rhythmic Light Therapy to Entrain Gamma Oscillations and the Circadian System in Patients With Alzheimer's Disease

Anticipated Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Dec 31, 2025

Anticipated Study Completion Date :

Dec 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Active Intervention plus Active Rhythm The device will set on a tabletop in a room where the participant spends at least 2 hours in the morning. Using a timer, it will automatically turn on at preferred wakeup times (but no later than 09:00 am) chosen by the participant. Lights will remain on for at least 2 hours and participants will be asked to remain the space that lights are being applied for that period of time.	Device: Circadian-Effective Light Narrowband blue light Other Names: Active Light Device: Rhythmic Light 40 hertz (Hz) flicker
Active Comparator: Active Light plus Placebo Rhythm The device will set on a tabletop in a room where the participant spends at least 2 hours in the morning. Using a timer, it will automatically turn on at preferred wakeup times (but no later than 09:00 am) chosen by the participant. Lights will remain on for at least 2 hours and participants will be asked to remain the space that lights are being applied for that period of time.	Device: Circadian-Effective Light Narrowband blue light Other Names: Active Light Device: Placebo Rhythmic Light Random flicker for placebo rhythmic effect
Active Comparator: Placebo Light plus Active Rhythm The device will set on a tabletop in a room where the participant spends at least 2 hours in the morning. Using a timer, it will automatically turn on at preferred wakeup times (but no later than 09:00 am) chosen by the participant. Lights will remain on for at least 2 hours and participants will be asked to remain the space that lights are being applied for that period of time.	Device: Rhythmic Light 40 hertz (Hz) flicker Device: Placebo Light Narrowband red light
Placebo Comparator: Placebo Light plus Placebo Rhythm The device will set on a tabletop in a room where the participant spends at least 2 hours in the morning. Using a timer, it will automatically turn on at preferred wakeup times (but no later than 09:00 am) chosen by the participant. Lights will remain on for at least 2 hours and participants will be asked to remain the space that lights are being applied for that period of time.	Device: Placebo Light Narrowband red light Device: Placebo Rhythmic Light Random flicker for placebo rhythmic effect

Outcome Measures

Primary Outcome Measures

Cognition using the Montreal Cognitive Assessment (MoCA) [baseline]
The Montreal Cognitive Assessment is a one-page, 30-point test that can be administered in 10 minutes. It assesses short-term memory, visuospatial abilities, executive functions, attention, concentration and working memory, language, and orientation to time and place. total score ranging from 0 to 30 units on a scale, with higher score indicating better cognitive global function.
Cognition using the Montreal Cognitive Assessment (MoCA) [at the end of week 9]
The Montreal Cognitive Assessment is a one-page, 30-point test that can be administered in 10 minutes. It assesses short-term memory, visuospatial abilities, executive functions, attention, concentration and working memory, language, and orientation to time and place. total score ranging from 0 to 30 units on a scale, with higher score indicating better cognitive global function.
Cognition using the Montreal Cognitive Assessment (MoCA) [at the end of week 14]
The Montreal Cognitive Assessment is a one-page, 30-point test that can be administered in 10 minutes. It assesses short-term memory, visuospatial abilities, executive functions, attention, concentration and working memory, language, and orientation to time and place. total score ranging from 0 to 30 units on a scale, with higher score indicating better cognitive global function.

Secondary Outcome Measures

Cognition using a working memory task [baseline]
Participants view a serial visual display of letters and math problems. They are asked to hold the letters in memory while simultaneously determining if the simple math problems are correct (e.g., 7+5=13). Math performance is measured in percent correct and verbal performance is assessed by calculating Accuracy and Reaction Time (RT).
Cognition using a working memory task [at the end of week 9]
Participants view a serial visual display of letters and math problems. They are asked to hold the letters in memory while simultaneously determining if the simple math problems are correct (e.g., 7+5=13). Math performance is measured in percent correct and verbal performance is assessed by calculating Accuracy and Reaction Time (RT).
Cognition using a working memory task [at the end of week 14]
Participants view a serial visual display of letters and math problems. They are asked to hold the letters in memory while simultaneously determining if the simple math problems are correct (e.g., 7+5=13). Math performance is measured in percent correct and verbal performance is assessed by calculating Accuracy and Reaction Time (RT).
Cognition using a word pair associates task [baseline]
Participants are presented with 48 word-pairs in the evening. Recognition tests are assessed both immediately following the encoding session, and delayed during retrieval.
Cognition using a word pair associates task [at the end of week 9]
Participants are presented with 48 word-pairs in the evening. Recognition tests are assessed both immediately following the encoding session, and delayed during retrieval.
Cognition using a word pair associates task [at the end of week 14.]
Participants are presented with 48 word-pairs in the evening. Recognition tests are assessed both immediately following the encoding session, and delayed during retrieval.
Cognition using an implicit priming task [baseline]
Participants will be presented with simple pictures of objects and animals. Following a break, the participant will then be asked to identify a larger set of pictures as soon as he/she is able to do so as the pictures clarify over time; some of these test pictures were shown previously and some are new.
Cognition using an implicit priming task [at the end of week 9]
Participants will be presented with simple pictures of objects and animals. Following a break, the participant will then be asked to identify a larger set of pictures as soon as he/she is able to do so as the pictures clarify over time; some of these test pictures were shown previously and some are new.
Cognition using an implicit priming task [at the end of week 14.]
Participants will be presented with simple pictures of objects and animals. Following a break, the participant will then be asked to identify a larger set of pictures as soon as he/she is able to do so as the pictures clarify over time; some of these test pictures were shown previously and some are new.
Cognition using the Alzheimer's Disease Assessment Scale - Cognitive Subscale [baseline]
This interview-style test assesses multiple cognitive domains such as memory, language, praxis, and orientation. The ADAS-Cog subscale is scored from 0-100. The full ADAS is scored from 0 to 150 by summing the number of errors made on each task so that higher scores indicate worse performance.
Cognition using the Alzheimer's Disease Assessment Scale - Cognitive Subscale [at the end of week 9]
This interview-style test assesses multiple cognitive domains such as memory, language, praxis, and orientation. The Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) subscale is scored from 0-100. The full ADAS is scored from 0 to 150 by summing the number of errors made on each task so that higher scores indicate worse performance.
Cognition using the Alzheimer's Disease Assessment Scale - Cognitive Subscale [at the end of week 14.]
This interview-style test assesses multiple cognitive domains such as memory, language, praxis, and orientation. The ADAS-Cog subscale is scored from 0-100. The full ADAS is scored from 0 to 150 by summing the number of errors made on each task so that higher scores indicate worse performance.
Urine Melatonin Biomarker [baseline]
Urine Melatonin Biomarker via urine collection
Urine Melatonin Biomarker [at the end of week 9.]
Urine Melatonin Biomarker via urine collection
Light Exposure using a Daysimeter [baseline]
The Daysimeter will also be used to monitor the total amount of circadian light received by the participant during the study.
Light Exposure using a Daysimeter [week 9]
The Daysimeter will also be used to monitor the total amount of circadian light received by the participant during the study.
Light Exposure using a Daysimeter [week 14.]
The Daysimeter will also be used to monitor the total amount of circadian light received by the participant during the study.
Sleep Quantity using Actigraphy [baseline]
Sleep Quantity measured using Actigraphy
Sleep Quantity using Actigraphy [week 9]
Sleep Quantity measured using Actigraphy
Sleep Quantity using Actigraphy [week 14]
Sleep Quantity measured using Actigraphy
Sleep Quality using the Pittsburgh Sleep Quality Index (PSQI) [baseline]
The Pittsburgh Sleep Quality Index is a tool that can be used to measure sleep quality in clinical populations, composed of 19 items that generate 7 component scores (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction). Each item is weighted on a 0-3 interval scale. The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, with higher score indicates worse sleep quality
Sleep Quality using the Pittsburgh Sleep Quality Index (PSQI) [at the end of week 9]
The Pittsburgh Sleep Quality Index is a tool that can be used to measure sleep quality in clinical populations, composed of 19 items that generate 7 component scores (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction). Each item is weighted on a 0-3 interval scale. The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, with higher score indicates worse sleep quality
Sleep Quality using the Pittsburgh Sleep Quality Index (PSQI) [at the end of week 14.]
The Pittsburgh Sleep Quality Index is a tool that can be used to measure sleep quality in clinical populations, composed of 19 items that generate 7 component scores (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction). Each item is weighted on a 0-3 interval scale. The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, with higher score indicates worse sleep quality
Quality of Life using the Dementia Quality of Life Instrument [baseline]
The Dementia Quality of Life Instrument (DQoL) measures self-esteem, positive affect/humor, negative affect, feelings of belonging, and sense of aesthetics.The DQoL consists of 29 items, grouped into 5 subscales according to domain. Subjects are instructed to answer using a 5-point response scale (score from 1-5), either verbally or through use of a visual scale. Scores for each subscale are Self-esteem (4-20), Positive Affect/Humor (6-30), Absence of Negative Affect (11-55), Feelings of Belonging (3-15), Sense of Aesthetics (5-25); however, subscale scores are not summed for a total score. A higher number indicates greater quality of life.
Quality of Life using the Dementia Quality of Life Instrument [at the end of week 9]
The Dementia Quality of Life Instrument (DQoL) measures self-esteem, positive affect/humor, negative affect, feelings of belonging, and sense of aesthetics.The DQoL consists of 29 items, grouped into 5 subscales according to domain. Subjects are instructed to answer using a 5-point response scale (score from 1-5), either verbally or through use of a visual scale. Scores for each subscale are Self-esteem (4-20), Positive Affect/Humor (6-30), Absence of Negative Affect (11-55), Feelings of Belonging (3-15), Sense of Aesthetics (5-25); however, subscale scores are not summed for a total score. A higher number indicates greater quality of life.
Quality of Life using the Dementia Quality of Life Instrument [at the end of week 14.]
The Dementia Quality of Life Instrument (DQoL) measures self-esteem, positive affect/humor, negative affect, feelings of belonging, and sense of aesthetics.The DQoL consists of 29 items, grouped into 5 subscales according to domain. Subjects are instructed to answer using a 5-point response scale (score from 1-5), either verbally or through use of a visual scale. Scores for each subscale are Self-esteem (4-20), Positive Affect/Humor (6-30), Absence of Negative Affect (11-55), Feelings of Belonging (3-15), Sense of Aesthetics (5-25); however, subscale scores are not summed for a total score. A higher number indicates greater quality of life.

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participants must be diagnosed with amnestic mild cognitive impairment or mild Alzheimer's disease, as defined by a Montreal Cognitive Assessment score between 17 and 25;
Have sleep disturbance indicated by a score >5 on the Pittsburgh Sleep Quality Index
Sleep efficiency < 80% assessed by wearing an actigraph for 3 days
Participants must reside in their homes, independent living, or assisted living facilities

Exclusion Criteria:

Participants taking sleep medication
Presence of another brain disease that fully explains the dementia (extensive brain vascular disease, Parkin-son's disease, dementia with Lewy bodies, traumatic brain injury, or multiple sclerosis)
Residence in a skilled nursing facility or long-term care
Major organ failure (e.g., kidney failure)
Uncontrolled generalized disorders such as hypertension or diabetes
Obstructing cataracts, macular degeneration, and blindness
Severe sleep apnea or restless leg syndrome
History of severe epilepsy