Morning light treatment for inflammatory bowel disease: a clinical trial.

BACKGROUND: Inflammatory bowel disease (IBD) affects over 3 million Americans and has a relapsing and remitting course with up to 30% of patients experiencing exacerbations each year despite the availability of immune targeted therapies. An urgent need exists to develop adjunctive treatment approaches to better manage IBD symptoms and disease activity. Circadian disruption is associated with increased disease activity and may be an important modifiable treatment target for IBD. Morning light treatment, which advances and stabilizes circadian timing, may have the potential to improve IBD symptoms and disease activity, but no studies have explored these potential therapeutic benefits in IBD. Therefore, in this study, we aim to test the effectiveness of morning light treatment for patients with IBD. METHODS: We will recruit sixty-eight individuals with biopsy-proven IBD and clinical symptoms and randomize them to 4-weeks of morning light treatment or 4-weeks of treatment as usual (TAU), with equivalent study contact. Patient-reported outcomes (IBD-related quality of life, mood, sleep), clinician-rated disease severity, and a biomarker of gastrointestinal inflammation (fecal calprotectin) will be assessed before and after treatment. Our primary objective will be to test the effect of morning light treatment versus TAU on IBD-related quality of life and our secondary objectives will be to test the effects on clinician-rated disease activity, depression, and sleep quality. We will also explore the effect of morning light treatment versus TAU on a biomarker of gastrointestinal inflammation (fecal calprotectin), and the potential moderating effects of steroid use, restless leg syndrome, and biological sex. DISCUSSION: Morning light treatment may be an acceptable, feasible, and effective adjunctive treatment for individuals with active IBD suffering from impaired health-related quality of life. TRIAL REGISTRATION: The study protocol was registered on ClinicalTrials.gov as NCT06094608 on October 23, 2023, before recruitment began on February 1, 2024.

Do sleep and circadian characteristics predict alcohol use in adult drinkers?

BACKGROUND: While sleep and circadian rhythms are recognized contributors to the risk for alcohol use and related problems, few studies have examined whether objective sleep and circadian measures can predict future alcohol use in humans, and no such studies have been conducted in adults. This study examined whether any baseline sleep and/or circadian characteristics of otherwise healthy adults predicted their alcohol use over the subsequent 12 months. METHODS: Participants (21-42 years) included 28 light and 50 heavy drinkers. At baseline, a comprehensive range of self-reported and objective sleep/circadian measures was assessed via questionnaires, wrist actigraphy, and measurement of dim light melatonin onset and circadian photoreceptor responsivity. Following this, the number of alcoholic drinks per week and binge drinking episodes per month were assessed quarterly over the subsequent 12 months. Anticipated effects of alcohol (stimulation, sedation, and rewarding aspects) were also assessed quarterly over the 12 months. Analyses included generalized linear mixed-effects models and causal mediation analysis. RESULTS: Across the range of measures, only self-reported insomnia symptoms and a longer total sleep time at baseline predicted more drinks per week and binges per month (ps <0.02). There was a trend for the anticipated alcohol effect of wanting more alcohol at the 6-month timepoint to mediate the relationship between insomnia symptoms at baseline and drinks per week at 12 months (p = 0.069). CONCLUSIONS: These results suggest that in otherwise healthy adults, insomnia symptoms, even if subclinical, are a significant predictor of future drinking, and appear to outweigh the influence of circadian factors on future drinking, at least in otherwise healthy adults. Insomnia symptoms may be a modifiable target for reducing the risk of alcohol misuse.

An independent comparison of the Novolytix salivary melatonin radioimmunoassay with the new Novolytix salivary melatonin enzyme-linked immunosorbent assay.

The dim light melatonin onset (DLMO) is the current gold standard biomarker of the timing of the central circadian clock in humans and is often assessed from saliva samples. To date, only one commercially available salivary melatonin assay is considered accurate at the low daytime levels required to accurately detect the DLMO (Novolytix RIA RK-DSM2). The aim of this study was to conduct the first independent evaluation of a newly improved enzyme-linked immunosorbent assay (ELISA; Novolytix MLTN-96) and compare it with the recommended radioimmunoassay (RIA)-both in terms of melatonin concentrations and derived DLMOs. Twenty participants (15 females, 18-59 years old) provided saliva samples every 30 min in dim light starting 6 h before their habitual bedtime, yielding a total of 260 saliva samples. Both the RIA and ELISA yielded daytime melatonin concentrations <2 pg/mL, indicating adequate accuracy to detect the DLMO. The melatonin concentrations from the two assays were highly correlated (r = .94, p < .001), although the RIA yielded lower levels of melatonin concentration than the ELISA, on average by 0.70 pg/mL (p = .006). Seventeen DLMOs were calculated from the melatonin profiles and the DLMOs from both assays were not statistically different (p = .36) and were highly correlated (r = .97, p < .001). Two DLMOs derived from the RIA occurred more than 30 min earlier than the DLMO derived from the ELISA. These results indicate that the new Novolytix ELISA is an appropriate assay to use if the Novolytix RIA is not feasible or available.

A 4-week morning light treatment with stable sleep timing for individuals with fibromyalgia: a randomized controlled trial.

OBJECTIVES: Fibromyalgia is characterized by chronic widespread pain, mood, and sleep disturbance. Pharmacological treatments have modest efficacy and are associated with negative side effects, and alternative approaches are needed. Morning bright light treatment may assist in the management of fibromyalgia as it can reduce depressive symptoms, improve sleep, and advance circadian timing. METHODS: Sixty people with fibromyalgia (58 women, mean age 41.8 ± 13.3 years) were enrolled in a study comparing 4 weeks of a 1-hour daily morning bright light treatment (active treatment) to a morning dim light treatment (comparison treatment). Both light treatments included behavioral procedures to stabilize sleep timing. The morning bright light treatment was expected to produce larger improvements in pain and function than the dim light treatment and larger improvements in potential mediators (mood, sleep, and circadian timing). RESULTS: Both the bright and dim light treatment groups achieved significant but similar levels of improvement in pain intensity, pain interference, physical function, depressive symptoms, and sleep disturbance. Overall, the sample on average displayed a clinically meaningful improvement in the Fibromyalgia Impact Questionnaire-Revised score (mean reduction of 11.2 points), comparable to that reported following physical exercise treatments. Minimal side effects were observed. CONCLUSIONS: Findings indicate that the effects of a morning bright light treatment did not exceed those of a comparison dim light treatment; yet the changes on average in both conditions revealed clinically meaningful improvements. Future research is warranted to identify what elements of this trial may have contributed to the observed effects.

Sleep and circadian differences between light and heavy adult alcohol drinkers.

BACKGROUND: Numerous studies have reported that eveningness is associated with increased alcohol consumption. However, biological markers of circadian timing, such as dim light melatonin onset (DLMO) and circadian photoreceptor responsivity (post-illumination pupil response, PIPR), have rarely been assessed in the context of habitual alcohol consumption. This study aimed to examine sleep, circadian timing, and photoreceptor responsivity in adult alcohol drinkers. METHODS: Participants (21 to 45 years) included 28 light and 50 heavy drinkers. The 8-day study consisted of a week of ad lib sleep monitored with wrist actigraphy, followed by a 9-h laboratory session with a photoreceptor responsivity and circadian phase assessment. RESULTS: The heavy drinkers obtained on average 28 more minutes of sleep (p = 0.002) and reported more eveningness than the light drinkers (p = 0.029). There was a trend for a shorter DLMO-midsleep interval (p = 0.059) in the heavy drinkers, reflecting a tendency for them to sleep at an earlier circadian phase. The PIPR in the heavy drinkers was significantly smaller than in the light drinkers (p = 0.032), suggesting reduced circadian photoreceptor responsivity in the heavy drinkers. A larger PIPR was significantly associated with a later DLMO in the light drinkers (r = 0.44, p = 0.019), but this relationship was absent in the heavy drinkers (r = -0.01, p = 0.94). CONCLUSIONS: These results are consistent with earlier reports of more eveningness and a shorter DLMO-midsleep interval being associated with heavier alcohol drinking. The novel finding of reduced circadian photoreceptor responsivity in heavy drinkers is consistent with prior rodent studies. Future studies should explore the impact of habitual alcohol consumption on other measures of circadian photoreceptor responsivity.

The prevalence and impact of pre-existing sleep disorder diagnoses and objective sleep parameters in patients hospitalized for COVID-19.

STUDY OBJECTIVES: Obstructive sleep apnea and other sleep disorders overlap with comorbidities associated with poor outcomes related to severe acute respiratory syndrome coronavirus 2 infection. However, the prevalence of obstructive sleep apnea among patients hospitalized for COVID-19 and relationship to outcomes is poorly characterized, and the relevance of other sleep disorders remains unknown. The objective of this study was to identify the prevalence of pre-existing sleep disorders and association with outcomes related to severe COVID-19 illness. METHODS: Patients with severe acute respiratory syndrome coronavirus 2 infection admitted to the University of Michigan Hospital System were included. Electronic medical records were queried for sleep disorders diagnostic codes. Data were extracted from polysomnography and home sleep testing in a subgroup with previous diagnostic testing at our center. Logistic regression was used to examine the association of sleep disorders with mechanical ventilation requirement, treatment with vasopressors, and death and Cox proportional hazards regression for time to discharge. RESULTS: Among n = 572 adult patients hospitalized for COVID-19, 113 (19.8%) patients had obstructive sleep apnea, 4 patients had central sleep apnea (0.7%), 5 had hypoventilation (0.9%), 63 had insomnia (11.0%), and 22 had restless legs syndrome or periodic limb movements disorder (3.9%). After adjusting for age, sex, body mass index, and race, no significant relationship was apparent between sleep disorders diagnoses or indices of sleep-disordered breathing severity and outcomes. CONCLUSIONS: This is the first study to determine the prevalence of obstructive sleep apnea and other sleep disorders in a well-characterized cohort of patients hospitalized for COVID-19. Once hospitalized, a significant contribution of sleep disorders to outcomes was not identified. Therefore, future evaluations should focus on earlier outcomes, such as infection or clinical manifestations after exposure to severe acute respiratory syndrome coronavirus 2.

Morning Bright Light Treatment for Chronic Low Back Pain: Potential Impact on the Volatility of Pain, Mood, Function, and Sleep.

OBJECTIVES: Most treatment outcome studies for people with chronic low back pain (CLBP) have based analyses on and reported only the mean levels of these factors. However, high levels of pain, mood, function, and sleep volatility may represent unique factors contributing to diminished quality of life. Our goal was to determine whether bright light treatment affected both mean levels of pain, mood, function, and sleep and reduced volatility in these outcomes. METHODS: US military veterans with CLBP (N = 22) underwent an open trial with a seven-day baseline, followed by 13 days of a one-hour morning bright light treatment self-administered at their home and a 30-day follow-up. Participants completed daily diary measures at 12 Pm and 6 Pm every day during the three study epochs. RESULTS: Using location scale modeling, results suggested that, in addition to being associated with changes in mean levels of pain intensity, pain interference, negative affect, and sleep quality, bright light treatment was also related to reductions in the volatility of pain intensity and negative affect, reductions that were largely maintained during follow-up. CONCLUSIONS: Changes in mean levels and volatility were independent factors, suggesting that bright light treatment was related to participants experiencing fewer "pain flares." These findings underscore the potential importance of volatility as a future treatment target.

An Open Trial of Morning Bright Light Treatment Among US Military Veterans with Chronic Low Back Pain: A Pilot Study.

OBJECTIVE: To examine the feasibility, acceptability, and effects of a home-based morning bright light treatment on pain, mood, sleep, and circadian timing in US veterans with chronic low back pain. DESIGN: An open treatment trial with a seven-day baseline, followed by 13 days of a one-hour morning bright light treatment self-administered at home. Pain, pain sensitivity, mood, sleep, and circadian timing were assessed before, during, and after treatment. SETTING: Participants slept at home, with weekly study visits and home saliva collections. PARTICIPANTS: Thirty-seven US veterans with medically verified chronic low back pain. METHODS: Pain, mood, and sleep quality were assessed with questionnaires. Pain sensitivity was assessed using two laboratory tasks: a heat stimulus and an ischemia stimulus that gave measures of threshold and tolerance. Sleep was objectively assessed with wrist actigraphy. Circadian timing was assessed with the dim light melatonin onset. RESULTS: Morning bright light treatment led to reduced pain intensity, pain behavior, thermal pain threshold sensitivity, post-traumatic stress disorder symptoms, and improved sleep quality (P < 0.05). Phase advances in circadian timing were associated with reductions in pain interference (r = 0.55, P < 0.05). CONCLUSIONS: Morning bright light treatment is a feasible and acceptable treatment for US veterans with chronic low back pain. Those who undergo morning bright light treatment may show improvements in pain, pain sensitivity, and sleep. Advances in circadian timing may be one mechanism by which morning bright light reduces pain. Morning bright light treatment should be further explored as an innovative treatment for chronic pain conditions.

Do the Morningness-Eveningness Questionnaire and Munich ChronoType Questionnaire Change After Morning Light Treatment?

The Morningness-Eveningness Questionnaire (MEQ) and Munich ChronoType Questionnaire (MCTQ) are sometimes used to estimate circadian timing. However, it remains unclear if they can reflect a change in circadian timing after a light treatment. In this study, 31 participants (25-68 years) completed both questionnaires before and after a 13-28 day morning light treatment. The dim light melatonin onset (DLMO), a physiological marker of circadian timing, was also assessed in a subsample of 16 participants. The DLMO phase advanced on average by 47 minutes (p<0.001). The MEQ score increased by 1.8 points (p=0.046). The MSFsc measure derived from the MCTQ advanced by 8.7 minutes (p=0.17). The shift towards morningness observed in both questionnaires correlated with the phase advance observed in the DLMO (MEQ r=-0.46, p=0.036; MSFsc r=0.81, p<0.001). Results suggest that these circadian questionnaires can change in response to a light treatment, indicating they can reflect underlying changes in circadian timing.

Sleep and circadian variability in people with delayed sleep-wake phase disorder versus healthy controls.

OBJECTIVE/BACKGROUND: To compare sleep and circadian variability in adults with delayed sleep-wake phase disorder (DSWPD) to healthy controls. PATIENTS/METHODS: Forty participants (22 DSWPD, 18 healthy controls) completed a ten-day protocol, consisting of DLMO assessments on two consecutive nights, a five-day study break, followed by two more DLMO assessments. All participants were instructed to sleep within one hour of their self-reported average sleep schedule for the last four days of the study break. We analyzed the participants' wrist actigraphy data during these four days to examine intraindividual variability in sleep timing, duration and efficiency. We also examined shifts in the DLMO from before and after the study break. RESULTS AND CONCLUSIONS: Under the same conditions, people with DSWPD had significantly more variable wake times and total sleep time than healthy controls (p ≤ 0.015). Intraindividual variability in sleep onset time and sleep efficiency was similar between the two groups (p ≥ 0.30). The DLMO was relatively stable across the study break, with only 11% of controls but 27% of DSWPDs showed more than a one hour shift in the DLMO. Only in the DSWPD sample was greater sleep variability associated with a larger shift in the DLMO (r = 0.46, p = 0.03). These results suggest that intraindividual variability in sleep can be higher in DSWPD versus healthy controls, and this may impact variability in the DLMO. DSWPD patients with higher intraindividual variability in sleep are more likely to have a shifting DLMO, which could impact sleep symptoms and the optimal timing of light and/or melatonin treatment for DSWPD. CLINICAL TRIAL: Circadian Phase Assessments at Home, http://clinicaltrials.gov/show/NCT01487252, NCT01487252.

A single dose of alcohol does not meaningfully alter circadian phase advances and phase delays to light in humans.

Central circadian timing influences mental and physical health. Research in nocturnal rodents has demonstrated that when alcohol is consumed, it reaches the central hypothalamic circadian pacemaker (suprachiasmatic nuclei) and can directly alter circadian phase shifts to light. In two separate studies, we examined, for the first time, the effects of a single dose of alcohol on circadian phase advances and phase delays to light in humans. Two 23-day within-subjects placebo-controlled counterbalanced design studies were conducted. Both studies consisted of 6 days of fixed baseline sleep to stabilize circadian timing, a 2-day laboratory session, a 6-day break, and a repeat of 6 days of fixed sleep and a 2-day laboratory session. In the phase advance study (n= 10 light drinkers, 24-45 yr), the laboratory sessions consisted of a baseline dim light phase assessment, sleep episode, alcohol (0.6 g/kg) or placebo, 2-h morning bright light pulse, and final phase assessment. In the phase-delay study (n= 14 light drinkers, 22-44 yr), the laboratory sessions consisted of a baseline phase assessment, alcohol (0.8 g/kg) or placebo, 2-h late night bright light pulse, sleep episode, and final phase assessment. In both studies, alcohol either increased or decreased the observed phase shifts to light (interaction P≥ 0.46), but the effect of alcohol vs. placebo on phase shifts to light was always on average smaller than 30 min. Thus, no meaningful effects of a single dose of alcohol vs. placebo on circadian phase shifts to light in humans were observed.