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

Mild Cognitive Impairment Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05016219
• Other study ID #: GCO 21-0378-02
• Status: Recruiting
• Phase: N/A
• Start date: August 22, 2023
• Est. completion date: December 31, 2026

Study information

• Verified date: September 2023
• Source: Icahn School of Medicine at Mount Sinai
• Contact: Barbara Plitnick, BSN
• Phone: 518-242-4603
• Email: barbara.plitnick[@]mountsinai.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

Inclusion Criteria:

• Participants must be diagnosed with 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
• Participants must reside in their homes, independent living, or assisted living facilities

Exclusion Criteria:

• Participants taking sleep medication
• Residence in a skilled nursing facility or long-term care
• Obstructing cataracts, macular degeneration, and blindness
• Severe sleep apnea or restless leg syndrome
• History of severe epilepsy

Related Conditions & MeSH terms

• Alzheimer Disease
• Cognitive Dysfunction
• Mild Cognitive Impairment

Intervention

Device:
• Circadian-Effective Light
Narrowband blue light
• Rhythmic Light
40 hertz (Hz) flicker
• Placebo Light
Narrowband red light
• Placebo Rhythmic Light
Random flicker for placebo rhythmic effect

Locations

Country	Name	City	State
United States	Light and Health Research Center	Menands	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai

Country where clinical trial is conducted

United States, 

References & Publications (8)

Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. doi: 10.1016/0165-1781(89)90047-4. — View Citation

Buysse DJ, Reynolds CF 3rd, Monk TH, Hoch CC, Yeager AL, Kupfer DJ. Quantification of subjective sleep quality in healthy elderly men and women using the Pittsburgh Sleep Quality Index (PSQI). Sleep. 1991 Aug;14(4):331-8. Erratum In: Sleep 1992 Feb;15(1):83. — View Citation

Figueiro MG, Hamner R, Bierman A, Rea MS. Comparisons of three practical field devices used to measure personal light exposures and activity levels. Light Res Technol. 2013 Aug;45(4):421-434. doi: 10.1177/1477153512450453. — View Citation

Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL. A new clinical scale for the staging of dementia. Br J Psychiatry. 1982 Jun;140:566-72. doi: 10.1192/bjp.140.6.566. — View Citation

McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984 Jul;34(7):939-44. doi: 10.1212/wnl.34.7.939. — View Citation

Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x. Erratum In: J Am Geriatr Soc. 2019 Sep;67(9):1991. — View Citation

Rea MS, Figueiro MG, Bullough JD, Bierman A. A model of phototransduction by the human circadian system. Brain Res Brain Res Rev. 2005 Dec 15;50(2):213-28. doi: 10.1016/j.brainresrev.2005.07.002. Epub 2005 Oct 7. Erratum In: Brain Res Brain Res Rev. 2007 Nov;56(1):270. — View Citation

Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer's disease. Am J Psychiatry. 1984 Nov;141(11):1356-64. doi: 10.1176/ajp.141.11.1356. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cognition using the Montreal Cognitive Assessment (MoCA)	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.	baseline
Primary	Cognition using the Montreal Cognitive Assessment (MoCA)	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.	at the end of week 9
Primary	Cognition using the Montreal Cognitive Assessment (MoCA)	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.	at the end of week 14
Secondary	Cognition using a working memory task	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).	baseline
Secondary	Cognition using a working memory task	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).	at the end of week 9
Secondary	Cognition using a working memory task	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).	at the end of week 14
Secondary	Cognition using a word pair associates task	Participants are presented with 48 word-pairs in the evening. Recognition tests are assessed both immediately following the encoding session, and delayed during retrieval.	baseline
Secondary	Cognition using a word pair associates task	Participants are presented with 48 word-pairs in the evening. Recognition tests are assessed both immediately following the encoding session, and delayed during retrieval.	at the end of week 9
Secondary	Cognition using a word pair associates task	Participants are presented with 48 word-pairs in the evening. Recognition tests are assessed both immediately following the encoding session, and delayed during retrieval.	at the end of week 14.
Secondary	Cognition using an implicit priming task	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.	baseline
Secondary	Cognition using an implicit priming task	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.	at the end of week 9
Secondary	Cognition using an implicit priming task	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.	at the end of week 14.
Secondary	Cognition using the Alzheimer's Disease Assessment Scale - Cognitive Subscale	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.	baseline
Secondary	Cognition using the Alzheimer's Disease Assessment Scale - Cognitive Subscale	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.	at the end of week 9
Secondary	Cognition using the Alzheimer's Disease Assessment Scale - Cognitive Subscale	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.	at the end of week 14.
Secondary	Urine Melatonin Biomarker	Urine Melatonin Biomarker via urine collection	baseline
Secondary	Urine Melatonin Biomarker	Urine Melatonin Biomarker via urine collection	at the end of week 9.
Secondary	Light Exposure using a Daysimeter	The Daysimeter will also be used to monitor the total amount of circadian light received by the participant during the study.	baseline
Secondary	Light Exposure using a Daysimeter	The Daysimeter will also be used to monitor the total amount of circadian light received by the participant during the study.	week 9
Secondary	Light Exposure using a Daysimeter	The Daysimeter will also be used to monitor the total amount of circadian light received by the participant during the study.	week 14.
Secondary	Sleep Quantity using Actigraphy	Sleep Quantity measured using Actigraphy	baseline
Secondary	Sleep Quantity using Actigraphy	Sleep Quantity measured using Actigraphy	week 9
Secondary	Sleep Quantity using Actigraphy	Sleep Quantity measured using Actigraphy	week 14
Secondary	Sleep Quality using the Pittsburgh Sleep Quality Index (PSQI)	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	baseline
Secondary	Sleep Quality using the Pittsburgh Sleep Quality Index (PSQI)	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	at the end of week 9
Secondary	Sleep Quality using the Pittsburgh Sleep Quality Index (PSQI)	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	at the end of week 14.
Secondary	Quality of Life using the Dementia Quality of Life Instrument	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.	baseline
Secondary	Quality of Life using the Dementia Quality of Life Instrument	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.	at the end of week 9
Secondary	Quality of Life using the Dementia Quality of Life Instrument	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.	at the end of week 14.