Light Exposure for Insomnia

(NASC Trial)

Overseen By Daniela Grimaldi, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Northwestern University

Must not be taking: Psychoactive, Hypnotic, Stimulant, others

Disqualifiers: Sleep apnea, Neurological disorders, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4-5 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This study investigates the relationship between the noradrenergic (NA) system, sleep quality, and cognitive function in older adults with insomnia - a population at elevated risk for Alzheimer's disease-related dementias (ADRD) - compared to age and sex matched controls with normal sleep. The study characterizes NA function through multiple approaches: measuring 24-hour plasma levels of norepinephrine (NE) and its brain metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG); evaluating central NA system response using the clonidine suppression test (a presynaptic α2 adrenoreceptor agonist that reduces locus coeruleus NA activity; and employing pupillometry as a non-invasive marker of autonomic function. To explore NA function's mechanistic role in insomnia, the study uses an intervention with bright light exposure to enhance daytime NA activity, with the goal of improving both sleep quality and cognitive performance.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including psychoactive, hypnotic, stimulant, or analgesic medications, as well as those affecting the noradrenergic system like B-blockers, SNRIs, and NDRIs. If you are on any of these, you would need to stop using them to participate.

What data supports the effectiveness of the treatment Light Exposure, Bright Light Therapy, Light Therapy, Phototherapy for insomnia?

Research shows that bright light therapy can significantly improve sleep in people with insomnia by reducing the time they stay awake after initially falling asleep. It has also been effective in treating other sleep and mood disorders, suggesting it can help regulate sleep patterns. ^{1 2 3 4 5}

Is light therapy safe for humans?

Light therapy is generally safe for humans, with some studies reporting mild side effects like headache, eye strain, irritability, and nausea. However, these side effects are not common and can often be minimized with proper setup and usage. ^{2 6 7 8 9}

How does light exposure treatment for insomnia differ from other treatments?

Light exposure treatment for insomnia is unique because it uses bright light therapy to adjust the body's internal clock, helping to delay or advance sleep times without medication. This approach is particularly effective for those with circadian rhythm disorders and offers a non-drug alternative to traditional sleeping pills. ^{2 5 10 11 12}

Research Team

Daniela Grimaldi, MD, PhD

Principal Investigator

Northwestern University

Phyllis C Zee, MD, PhD

Principal Investigator

Northwestern University

Eligibility Criteria

This trial is for older adults who have trouble sleeping, known as insomnia. Participants should be at risk for memory-related diseases but can't join if they don't match the age and sex criteria or have other factors that could affect the study results.

Inclusion Criteria

I have been diagnosed with chronic insomnia.

I often wake up too early or sleep less than 80% of the time I'm in bed.

I've been awake for 60+ minutes in the middle of the night, at least 3 nights a week for the last month.

Exclusion Criteria

I am not taking medications that affect my pupils.

Habitual bedtime before 9pm or morning awakening before 5am

I am not taking medications like B-blockers or SNRIs that affect the nervous system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily exposure to bright light or dim red light for 28 (+4) days, with weekly phone calls to monitor compliance and side effects

4-5 weeks

Weekly phone calls

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Light Exposure

Trial Overview The study looks at how a part of the nervous system involved in alertness affects sleep and thinking in those with insomnia. It tests whether bright light exposure during the day can improve sleep quality and mental function by changing this system's activity.

Participant Groups

Group I: Intervention on Subjects with Insomnia Experimental Treatment 1 Intervention

The intervention in this study will involve 28 (+4) days of daily exposure to bright light (BL) for two 60-minute sessions (morning and afternoon). For the intervention, we will use Re-Timer® light glasses emitting light with an intensity of 230μW/cm2 (\~500lux) with a green blue 500nm dominant wavelength (between 480-520nm). Light with these characteristics has been shown effective in suppressing melatonin levels supporting their potential to exert effects on other biological non-visual functions associated with exposure to light relevant for this study. Throughout the intervention, participants will keep a diary to monitor daily use of the glasses. Participants will have weekly phone calls with the research team to encourage compliance and monitor potential side effects.

Group II: Dim Red Light Active Control 1 Intervention

Participants randomized to the control group will wear for two 60-minute sessions (morning and afternoon) customized dim-red light (RL) control Re-Timer® light glasses (wavelength peak at 632nm, light intensity \< 3 lux). Participants will be instructed to wear the light glasses in habitual indoor environments, without engaging in strenuous activities. Throughout the intervention, participants will keep a diary to monitor daily use of the glasses. Participants will have weekly phone calls with the research team to encourage compliance and monitor potential side effects.

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Findings from Research

Light therapy is an effective, evidence-based treatment for Seasonal Affective Disorder, influencing circadian rhythms that affect sleep, mood, and cognition, based on 40 years of clinical trials.

For optimal results, light therapy should use devices that provide 10,000 lux of white light for 30-60 minutes in the early morning, with ongoing monitoring to adjust treatment as needed and manage any side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CME: Light Therapy: Why, What, for Whom, How, and When (And a Postscript about Darkness). Wirz-Justice, A., Terman, AM.[2022]

Bright light therapy has been shown to significantly improve wake after sleep onset (WASO) in individuals with insomnia, based on a meta-analysis of 22 studies involving 685 participants.

While light therapy did not affect other sleep measures like sleep latency or total sleep time, it demonstrated potential for personalized treatment approaches by adjusting light exposure based on the type of insomnia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Light therapy in insomnia disorder: A systematic review and meta-analysis. Chambe, J., Reynaud, E., Maruani, J., et al.[2023]

A study involving 51 older adults with insomnia found that exposure to bright light did not significantly improve sleep quality compared to dim light, suggesting that bright light therapy may not be effective for this population.

While bright light exposure did shift the circadian phase, it did not lead to meaningful changes in either subjective or objective sleep measures, indicating that other factors may influence sleep in older individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Scheduled bright light for treatment of insomnia in older adults. Friedman, L., Zeitzer, JM., Kushida, C., et al.[2021]

Light therapy is being used more frequently to treat various sleep and psychiatric conditions, such as circadian rhythm sleep disorders and seasonal affective disorder, highlighting its growing importance in clinical practice.

Understanding the neural mechanisms behind circadian rhythms is essential for leveraging light therapy effectively, as it can significantly influence brain function and improve mood and sleep disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Illuminating rationale and uses for light therapy. Shirani, A., St Louis, EK.[2021]

In a study of 24 healthy adults with early-morning awakening insomnia, two evenings of bright-light therapy resulted in significant phase delays of circadian rhythms, including temperature and melatonin, indicating a shift in their internal body clock.

The bright-light therapy group experienced improved sleep outcomes, such as reduced time awake after sleep onset and increased total sleep time, along with fewer negative daytime symptoms, including reduced feelings of depression, lasting for up to 4 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The treatment of early-morning awakening insomnia with 2 evenings of bright light. Lack, L., Wright, H., Kemp, K., et al.[2019]

Light therapy (LT) significantly improved daytime sleepiness in patients with insomnia, as measured by the Epworth Sleepiness Scale, after a two-week treatment period involving 14 participants.

While LT showed benefits for sleep-related parameters, there were no significant changes in serum cortisol levels or clock genes' expression, indicating that the mechanism of action may not involve these biological markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and Efficacy of Morning Light Therapy for Adults with Insomnia: A Pilot, Randomized, Open-Label, Two-Arm Study. Yoon, J., Heo, S., Lee, H., et al.[2023]

In a study involving 42 patients with major depressive disorder, both bright white-light therapy (2,500 lux) and dim red-light therapy (50 lux) were administered daily for seven days without any significant differences in side effects between the two treatments.

This suggests that light therapy, regardless of intensity, may be a safe option for treating depression without increasing the risk of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side-effects of phototherapy in nonseasonal depressive disorder. Volz, HP., Mackert, A., Stieglitz, RD.[2004]

A study involving healthy young adults found that a single 30-minute session of bright light therapy (10,000 lux) did not lead to significantly more side effects compared to dim red light exposure, suggesting it is safe for short-term use in this population.

While both groups reported slight increases in eye strain and blurred vision, these effects were not significantly higher in the bright light therapy group, indicating that adverse effects may be less common in non-clinical populations than previously thought.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The acute side effects of bright light therapy: a placebo-controlled investigation. Botanov, Y., Ilardi, SS.[2023]

In a study involving 20 healthy participants, a new bright light therapy (BLT) cabin showed no reports of headaches, which are a common side effect of conventional BLT devices.

While some participants experienced blurring of vision (21.1% prevalence), the absence of headaches suggests that this new technology may improve patient adherence to treatment for seasonal depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bright light therapy: Minimizing light induced side effects with an innovative light setup. Leichtfried, V., Kantner-Rumplmair, W., Bartenbach, C., et al.[2014]

In a pilot study involving nine early morning awakening insomniacs, exposure to bright light in the evening successfully delayed their circadian rhythms, with temperature markers shifting by 2-4 hours and melatonin markers by 1-2 hours.

This bright light treatment led to a significant improvement in sleep patterns, delaying wake-up times from 4:59 AM to 6:11 AM and increasing total sleep time by over an hour, suggesting it could be an effective non-drug intervention for this type of insomnia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of evening bright light in delaying the circadian rhythms and lengthening the sleep of early morning awakening insomniacs. Lack, L., Wright, H.[2019]

Phototherapy is an effective treatment for various circadian sleep-wake disorders, including advanced and delayed sleep-wake phase disorders, non-24-hour sleep-wake rhythm disorder, jet lag, and night-shift work sleep-wake disorders.

The success of phototherapy relies on specific light characteristics such as intensity, duration, timing, and wavelength, but it should be avoided in patients with retinal disorders, necessitating consultation with an ophthalmologist.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treating circadian sleep-wake disorders by light]. Leger, D., Duforez, F., Gronfier, C.[2019]

Bright light therapy is effective for treating seasonal affective disorder and may also benefit various circadian rhythm sleep disorders, such as delayed and advanced sleep phase syndromes, based on a review of existing literature.

This therapy is relatively safe and its success relies on timing, suggesting that personalized approaches to treatment could enhance its effectiveness in managing sleep-wake rhythm misalignments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Photoperiod phototherapy and wakefulness-sleep rhythm disorders]. Poirrier, R.[2006]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

CME: Light Therapy: Why, What, for Whom, How, and When (And a Postscript about Darkness). [2022]

2. England pubmed.ncbi.nlm.nih.gov

Light therapy in insomnia disorder: A systematic review and meta-analysis. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Scheduled bright light for treatment of insomnia in older adults. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Illuminating rationale and uses for light therapy. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

The treatment of early-morning awakening insomnia with 2 evenings of bright light. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Feasibility and Efficacy of Morning Light Therapy for Adults with Insomnia: A Pilot, Randomized, Open-Label, Two-Arm Study. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

Side-effects of phototherapy in nonseasonal depressive disorder. [2004]

8. United States pubmed.ncbi.nlm.nih.gov

The acute side effects of bright light therapy: a placebo-controlled investigation. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Bright light therapy: Minimizing light induced side effects with an innovative light setup. [2014]

10. United States pubmed.ncbi.nlm.nih.gov

The effect of evening bright light in delaying the circadian rhythms and lengthening the sleep of early morning awakening insomniacs. [2019]

11. France pubmed.ncbi.nlm.nih.gov

[Treating circadian sleep-wake disorders by light]. [2019]

12. France pubmed.ncbi.nlm.nih.gov

[Photoperiod phototherapy and wakefulness-sleep rhythm disorders]. [2006]