Recruiting

Observational Study

Sponsor:

Northwestern University

Code:

NCT06694441

Conditions

Insomnia

Eligibility Criteria

Sex: All

Age: 55+

Healthy Volunteers: Accepted

Interventions

Light Exposure

Placebo

Study Details

Brief summary:

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.

Conditions

Insomnia

Study ID

NCT06694441

Start date

Sep 30, 2024

Status verified date

Mar, 2026

Completion date

Aug 31, 2029

Anticipated

Primary completion date

Jul 31, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 55+

Healthy Volunteers: Accepted

Inclusion Criteria:

1. Age ≥ 55 years;
2. Independent in activities of daily living and without clinically significant cognitive impairment as determined by a mini-mental status examination (MMSE) score ≥ 26;
3. Due to the effect of reproductive hormones on autonomic regulation, sleep and cognition, women will be postmenopausal;
4. time spent in bed not greater than 8.5 hours;
5. Sedentary, defined as participation in exercise of moderate intensity for less than 30 minutes per day and less than two times per week on a regular basis.
6. average daily light exposure indicative of indoor environments (from questionnaire).

Inclusion criteria for the insomnia group:

1. Meet criteria for chronic insomnia disorder according to the International Classification of Sleep Disorders (3rd Ed.);
2. Subjective sleep efficiency less than 85% and/or awakening earlier than desired if before 6 AM for ≥3 nights/week in the previous 4 weeks;
3. Subjective WASO (sWASO) ≥ 60 minutes for ≥3 nights/week in previous 4 weeks. sWASO will include time spent awake after sleep onset before final awakening + time spent awake in bed attempting to sleep after the final awakening;
4. global PSQI score greater than 5;
5. average daily light exposure indicative of indoor environments (from questionnaire).

Inclusion criteria for the control group:

1. No history of chronic or short-term insomnia disorder according to the International Classification of Sleep Disorders (3rd Ed.);
2. Subjective sleep efficiency greater than 85%;
3. Subjective mean total sleep time of 6.5 hours to 8 hours;
4. Habitual bedtime of 9PM-midnight;
5. PSQI score ≤ 5. Participants in the control group will be matched with the insomnia group on sex and age (±3 years).

Exclusion Criteria:

1. Sleep disorders other than insomnia (restless legs syndrome, parasomnias, REM behavior disorder, circadian rhythm sleep-wake disorder, sleep apnea by STOP questionnaire and apnea hypopnea index (AHI) ≥ 15 by home sleep apnea test;
2. habitual bedtime before 9pm or morning awakening before 5am;
3. History of neurological disorders;
4. History of psychiatric disorders;
5. A Beck depression inventory ((BDI-II) score greater than 19);
6. Unstable or serious medical conditions;
7. Prediabetes and diabetes (HbA1C ≥ 5.7)
8. Current, or use within the past month, of psychoactive, hypnotic, stimulant or analgesic medications (except occasionally);
9. Use of medications that interfere with NA system activity including B-blockers, selective serotonin and norepinephrine reuptake inhibitors (SNRIs) and selective norepinephrine-dopamine reuptake inhibitors (NDRIs);
10. Hormone replacement therapy;
11. Use of medications that affects pupil diameter and responses to light (i.e. antihistamines, anticholinergics, benzodiazepines, narcotics for pain;
12. History of visual abnormalities that may interfere with pupillary responses to light exposure such as significant cataracts, narrow-angle glaucoma or blindness;
13. History of heart conditions (i.e. arrhythmia, coronary artery disease, angina, heart failure);
14. Shift work or other types of self-imposed irregular sleep schedules;
15. BMI > 35 kg/m2;
16. History of habitual smoking (6 or more cigarettes/week) or caffeine consumption > 400 mg/day.

17.Use of weight-loss medications

Study Design

Enrollment

60 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Intervention on Subjects with Insomnia

The intervention in this study will involve 28 (+10) 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.

active comparator: Dim Red Light

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.

Interventions

Light Exposure

The intervention in this study will involve 28 (+10) 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.

Placebo

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).

Primary outcome measure

  • 24h plasma norepinephrine [ Time Frame: Enrollment to the end of treatment at 10 weeks. ]
  • Clonidine suppression test [ Time Frame: Enrollment ]
  • Wake after sleep onset (WASO) [ Time Frame: Enrollment to the end of treatment at 10 weeks. ]
  • Slow oscillatory activity during sleep [ Time Frame: Enrollment to the end of treatment at 10 weeks. ]
  • Pittsburg Sleep Quality Index [ Time Frame: Enrollment to the end of treatment at 10 weeks. ]
  • NIH tool box [ Time Frame: Enrollment to the end of treatment at 10 weeks. ]

Central Contacts and Locations

Locations

Northwestern University Feinberg School of Medicine, Center for Circadian and Sleep Medicine

Recruiting

Chicago, Illinois, United States, 60611

Contacts

Principal Investigator:

Daniela Grimaldi, MD, PhD

More Information

Sponsor

Northwestern University

Last update posted

Mar 30, 2026

Last verified

Mar, 2026

Keywords

  • Insomnia
  • Older Adults
  • Noradrenergic dysregulation
  • sleep
  • cognition
  • cognitive function

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Northwestern University on 2026-03-30.