Clinical Research Directory

Acupressure Therapy on Post-stroke Fatigue, Depression, and Sleep Disturbances in Ischemic Stroke Patients

Post-stroke fatigue (PSF) was defined as 'a subjective feeling of physical and/or mental exhaustion that is unrelated to exertion and does not typically improve with rest'. About 25\~85% of first stoke patients had PSF in the first year. Literature review from animal studies suggested the mechanism of post-stroke fatigue may be due to prolonged production of inflammatory cytokines process after stroke. Acupuncture therapy which regulates the inflammatory process may have the potential to ameliorate fatigue symptoms alone with sleep disturbance after stroke. Acupressure which stimulating the same acupoints by manually pressure may make it easy to perform in anytime and anywhere. The effect of circadian based acupressure application on post-stroke fatigue and sleep disturbances need be further examined. The purpose of this two-year study is to (1) explore the distribution of inflammatory cytokines (blood and urine IL-1β, IL-6, TNF-α, IL-8) and post-stroke fatigue and sleep, and (2) examine the effect of circadian-based acupressure application on the inflammatory cytokines (urine and blood IL-1β, IL-6, TNF-α, IL-8), and post-stroke symptoms fatigue and sleep) in ischemic stroke patients with post-stroke fatigue during rehabilitation. Ischemic stroke patients (N=240) will be assessed from the rehabilitation wards. Patients with fatigue (FAS\>=24) at assessment (n=78) will be further randomly assigned to the circadian based acupressure application group (AA), or the routine care control group (RC) for 2 weeks. Data of inflammatory cytokines (of IL-1β, IL-6, TNF-α, IL-8), post-stroke fatigue (Fatigue assessment scale), and sleep (Pittsburg Sleep Quality Index and consumer tracker) will be collected. Descriptive statistics, t-test, repeated measure ANOVA, linear/logistic regression or appropriate nonparametric equivalent will be used to compare pre-post differences and to compare differences between groups. Study results will provide information about the mechanism and effect of acupressure application on inflammation and post-stroke fatigue and sleep disturbances in ischemic stroke patients.

The Impact of Overnight Active Temperature Regulation on the Gut Microbiome, Inflammation, and Circadian Rhythm.

This study examines whether two continuous weeks of overnight active temperature regulation (via the Eight Sleep Pod) use affects gut microbiome composition, inflammation, and the body's daily temperature and blood pressure rhythms in postmenopausal women and age-matched men with self-reported poor sleep.

Examining the Circadian Timing Effects of the Hypotensive Response to Exercise

The goal of this study is to learn how exercise timing affects blood pressure in adults with elevated or high blood pressure. Exercise can influence the body's natural 24-hour rhythms, including blood pressure patterns. A single exercise session can lower blood pressure for up to 24 hours, but it is not fully understood how the time-of-day for exercise affects this response. The main question this study aims to answer is: • When the same participant exercises at different times of day (morning, afternoon, or evening), how does this affect the participant's blood pressure over the next 24 hours? Participants will: * Undergo an in-lab assessment of individual biological rhythm that will indicate the clock-time for an individual's biological night * Complete 3 supervised treadmill exercise sessions * 1 in the biological morning (biological night + 10 hours) * 1 in the biological afternoon (biological night + 15 hours) * 1 in the biological evening (biological night + 20 hours) * Complete a 24-hour blood pressure assessment before and after each exercise session

Circadian Rhythm and Cardiovascular Recovery After Submaximal Exercise

This cross-sectional, observational, and analytical study aims to investigate the relationship between morningness-eveningness characteristics and cardiovascular recovery after a submaximal exercise test in healthy individuals aged 18-45 years. Circadian preference will be assessed using the Morningness-Eveningness Questionnaire, sleep quality will be assessed using the Pittsburgh Sleep Quality Index, and cardiovascular recovery will be evaluated following the 6-Minute Walk Test

HEARTBEAT SOUND FOR BREASTFEEDİNG DİFFİCULTİES: A RANDOMİZED CONTROLLED TRİAL

This randomized controlled trial aims to evaluate the effect of listening to a pre-recorded, standardized maternal heartbeat sound on perceived stress levels and breastfeeding self-efficacy in mothers experiencing early breastfeeding difficulties. The study will be conducted in the postpartum service of a tertiary hospital. The results are expected to contribute to easily applicable, non-invasive, and supportive care approaches for breastfeeding support.

Timing and Resistance Exercise: Impact on Eating and Metabolism

Exercise timing (morning or evening) for optimal weight control is a research topic urgently addressed by scholars in the relevant field. Due to the better control of energy metabolism and physical activity levels in the morning, existing research on resistance exercise and eating behavior primarily focuses on experiments conducted in the morning, with only one study in the afternoon. No research has yet compared the potential differences between morning and evening resistance exercise. A one-year study aims to investigate the impact of morning and evening resistance exercise on physiological metabolism and eating behavior. Eighteen healthy male participants will be randomly assigned to a crossover design study, including AM exercise, PM exercise, and control (rest condition) trials. Variables including subjective appetite, appetite hormones (ghrelin, peptide YY), food preferences, ad libitum eating, dietary records, energy expenditure, and PBMCs circadian rhythm genes will be measured. This preliminary study through a multidimensional observation, the results will contribute to understanding the potential differences and mechanisms of morning and evening resistance exercise on physiological metabolism and eating behavior. In practical applications, conducting resistance exercise in the evening or at night aligns better with current lifestyles. The findings of this study can support the optimization of exercise benefits by validating the choice of exercise timing.

Food and Circadian Timing

The goals of this study are to uncover the influence of diet on the human circadian timing system. The protocol is a 46-day (28 outpatient days, 18 inpatient days over two 9 day visits) randomized cross-over study designed to elucidate the speed of entrainment in response to a high-fat diet.

Sleep and Circadian Rhythm Intervention in ICU

Intensive care unit (ICU) patients are frequently exposed to various stressors that contribute to severe sleep disruption and circadian rhythm disturbances. Growing evidence suggests that circadian rhythm disruption plays a critical role in the development of multiple adverse outcomes in critically ill patients. Therefore, implementing interventions that prioritize the maintenance of normal circadian, sleep, and behavioral patterns may represent an important strategy to improve outcomes in ICU patients.

Hyperthermia in Patients With Chronic Primary Pain - Effects on Thermoregulation, Somatosensory System and Movement Evoked Pain

This study, in a quasi-experimental matched two-group pre-post design, investigates the effect of serial water-filtered whole-body hyperthermia on circadian core body temperature, the somatosensory system (nociception) and the movement evoked pain in healthy and patients with chronic primary pain (e.g., fibromyalgia). The intervention lasts 3 weeks with two treatment sessions per week.

Sleep Loss and Circadian Misalignment - Mechanisms of Insulin Resistance

The purpose of this study is to examine the impact of timed cortisol release or differently timed cortisol rhythms on insulin resistance in both men and women undergoing sleep restriction. Chronic sleep loss is highly prevalent, affecting 1 in 3 adults in the US. Chronic sleep loss causes stress which induces insulin resistance and leads to obesity and type 2 diabetes. Many factors contribute to sleep loss including shift work, environmental disturbances, sleep/circadian disorders and comorbid medical and mental health conditions. Sleep loss increases the stress hormone cortisol in the evening and decreases daytime testosterone. Examining these hormones in a controlled laboratory environment under different sleep schedules may help researchers find solutions for adults experiencing negative health consequences related to chronic sleep loss.

Examination of Certain Blood Parameters Following Performance and Acute Exercise at Specific Times of the Day

This study aims to investigate whether the time of day at which acute exercise is performed influences physical performance and acute hormonal and biochemical responses in healthy young male soccer players. Participants will complete the same standardized exercise protocol in the morning (08:00-09:30) and evening (17:00-18:30), with a 96-hour interval between sessions. Performance will be assessed using vertical jump and Yo-Yo shuttle run tests. Blood samples will be collected before exercise, immediately after exercise, and two hours after exercise to assess testosterone, cortisol, creatine kinase, AST, ALT, LDH, and troponin levels. The study will examine whether exercise responses differ between morning and evening sessions and whether these differences are consistent with circadian variation.

Light Timing Study

Chronic circadian misalignment and sleep restriction peak during late adolescence, and are associated with morning daytime sleepiness, poor academic performance, conduct problems, depressed mood, suicidal ideation, substance use, insulin resistance, and obesity. Bright light exposure from light boxes can shift rhythms earlier (phase advance) to facilitate earlier sleep onset and reduce morning circadian misalignment and the associated risks. To phase advance circadian rhythms, the investigators' PRCs showed that the ideal time to begin light exposure was slightly before wake-up time and light should be avoided around bedtime because this is when light produces maximum phase delay shifts. An unexpected finding from these results, however, was a second advancing region in the afternoon (\~6 to 9 h after habitual wake-up time) suggesting that afternoon light may have more circadian phase advancing ability than traditionally thought. The overall goal of this mechanistic study is to follow-up on the unexpected PRC findings and test whether individually-timed afternoon light alone and in combination with morning bright light can shift circadian rhythms earlier in older adolescents. Four groups will be compared in a randomized parallel group design: afternoon bright light, morning bright light, morning + afternoon bright light, and a dim room light control. Adolescents will complete a 2-week protocol. After a baseline week with a stable sleep schedule, adolescents will live in the laboratory for 7 days. Sleep/dark and the time of bright light exposure will gradually shift earlier. Bright light (\~5000 lux) will be timed individually based on his/her stable baseline sleep schedule. The first 3-h morning bright light exposure will begin 1 h before wake on the first morning. The first 3-h afternoon bright light exposure will begin 5 h after wake. The morning + afternoon exposures will begin at the same times, but each exposure will be 1.5 h so that a total of 3 h of bright light per day will be given to each group except the dim light control group. Phase shifts of the circadian clocks marked by the dim light melatonin onset (DLMO) is the main outcome. Investigators hypothesize that afternoon bright light will work synergistically with morning bright light to produce larger shifts than morning or afternoon bright light alone. These data could challenge the current understanding of how to use bright light to shift circadian rhythms earlier.

Early Pregnancy Lifestyle and Glucose Patterns: A Substudy of TOFFFY

The goal of this clinical trial is to examine how daily behavioral patterns in early pregnancy, including sleep, physical activity, and meal timing, influence continuous glucose dynamics and subsequent risk of gestational diabetes mellitus (GDM) in pregnant women without pre-existing diabetes. The main questions it aims to answer are: 1. Do early-pregnancy chronobehavioral patterns (e.g., irregular sleep, night eating, and unstable rest-activity rhythms) relate to continuous glucose patterns measured using continuous glucose monitoring (CGM)? 2. Can early behavioral and CGM-derived measures predict glucose regulation and metabolic outcomes later in pregnancy (24-28 weeks)? 3. Does real-time self-monitoring using wearable devices and food logging improve glycemic outcomes compared to usual care? This study is a prospective, nested randomized pilot trial embedded within the ongoing Towards Optimal Fertility, Fathering and Fatherhood studY (TOFFFY) cohort (NCT06293235) at KK Women's and Children's Hospital, Singapore. A total of 140 pregnant women without pre-existing diabetes, recruited at ≤13 weeks gestation, will be randomized in a 1:1 ratio to either a pilot arm (wearable-based self-monitoring) or a control arm (usual care). Participants in the pilot arm (n=70) will undergo intensive behavioral and metabolic monitoring over a 14-day period in early pregnancy, including continuous glucose monitoring using a CGM device, wrist actigraphy to assess sleep-wake and rest-activity patterns, and an AI-supported mobile application to record meal timing and dietary intake. Participants will have real-time access to their glucose data and behavioral feedback, enabling self-monitoring and potential behavioral adjustments.

CIRCA-MED WP1 & WP3 - Circadian Rhythms in ICU Patients

The goal of this retrospective exploratory study is to examine how the body's natural day-and-night rhythms and oscillatory patterns behave in people who were treated in the Intensive Care Unit (ICU). The study uses routine clinical data that were already collected during and after the ICU stay, including post-discharge follow-up measurements (where available), such as heart rate, temperature, blood pressure, blood sugar, and insulin. The researchers want to learn whether these measurements show daily patterns and whether patients can be grouped based on their oscillatory profiles. The study also examines whether certain clinical factors such as illness severity scores, sedation levels, organ support treatments, or medications are associated with changes in these oscillatory rhythms. The team will explore whether conditions that can develop during or after critical illness, such as delirium, muscle weakness, or Post-Intensive Care Syndrome (PICS), are linked to disturbed physiological rhythms. Another goal is to test whether it is technically possible to show a patient's rhythm profile in real time using routine data from the ICU information system, evaluated retrospectively. Digital tools called "Chrono-Apps" will be developed to display rhythmic information and may help clinicians adjust lighting to patient needs.

Relationships Among Pupil Responses to Light, Circadian Rhythms, and Sleep

The investigators are studying relationships among eye pathology, pupil responses to light, sleep, circadian rhythms, and hormones in healthy individuals and those with various medical disorders or illnesses. All participants will: * Answer questionnaires about their health * Receive an eye exam, * For one week at home, participants will track their sleep and wake using actigraphy (wrist worn wearable) and an online sleep diary. * Complete a pupillometry session (measuring pupil size in response to different lighting) at MGH Participants may also choose to participate in the following additional procedures in any order: * Within one week of their pupillometry session, an at-home saliva collection under dim light. Saliva melatonin can be analyzed to determine Dim-Light-Melatonin-Onset (DLMO), a marker of circadian timing. * If participants participate in one night saliva collection, a second night of at-home saliva collection with a bright light exposure to calculate melatonin suppression in response to light.

Digital Insomnia and Circadian Therapy for Reducing Depression Symptoms in College Students

Depression is a leading cause of global disease burden, poor quality of life, disability and suicide, and commonly occurs in adolescence and early adulthood. Insomnia and circadian factors were regarded as potential targets for preventing worsening of depressive symptoms. Additionally, digital insomnia treatment reduces depressive symptoms but is insufficient for individuals with an evening chronotype. Circadian intervention is an adjunctive treatment for sleep disturbance and depression, but is often overlooked. In this study, we aim to evaluate the effect of guided digital insomnia and circadian intervention (dCBT-I + dCI) in reducing depressive symptoms in college students with insomnia and an evening chronotype compared with digital insomnia intervention alone (dCBT-I) and a health education group (dHE). We also aim to develop and evaluate multimodal prediction models to identify individuals who are more or less likely to respond to the interventions, using clinical, behavioral, circadian, and digital engagement data.

Dexmedetomidine Trial for Effects on Rhythms, Sleep Architecture, and Biomarker Dynamics in Older Adults

The DEXTER study is a cross-over, double-blind, placebo-controlled pilot research study led by Dr. Peng Li. The goal of this project is to evaluate the safety, feasibility, and biological effects of a single dose of sublingual (under-the-tongue) dexmedetomidine (SL Dex) in older adults. Specifically, researchers want to see how this medication affects sleep patterns, internal 24-hour circadian rhythms, and the daily cycles of certain neurological proteins (specifically plasma p-tau217) associated with brain aging.

Effect of Esketamine on Postoperative Sleep in Postmenopausal Women

The prevalence of sleep disturbance among postmenopausal women has been reported to reach 51.6%. Epidemiological studies consistently show that the incidence of sleep disorders increases with age and menopausal transition. Compared with premenopausal women, postmenopausal women demonstrate reduced circadian rhythm stability and a higher prevalence of sleep disturbance. In this population, levels of melatonin, total sleep time, sleep latency, N3 stage sleep, and the circadian amplitude of alertness are all diminished. Sleep disturbance can adversely affect both the mental and physical health of women and significantly impair their social functioning. Poor sleep is associated with decreased cognitive performance and heightened emotional distress, contributing to diminished quality of life. Circadian rhythms are endogenous physiological and behavioral cycles that oscillate over approximately 24 hours, governing critical processes such as sleep-wake cycles, hormonal fluctuations (e.g., cortisol and melatonin). These rhythms are regulated by the suprachiasmatic nucleus (SCN). Disruptions in circadian rhythms have been associated with sleep disturbances. Esketamine is the S (+) enantiomer of ketamine and has a higher affinity for the NMDA receptor than the R-enantiomer. Previous studies have demonstrated that intraoperative administration of esketamine can improve postoperative sleep quality and reduce the incidence of postoperative sleep disturbances, through its antidepressant efficacy, anti-inflammatory properties, analgesic efficacy, neurocognitive and anxiolytic effects. However, few studies have investigated whether esketamine can regulate perioperative circadian rhythms and subsequently affect sleep, especially in postmenopausal women. The objective of this multi-center, prospective, randomized controlled clinical trial is to investigate the effects of esketamine on postoperative sleep in postmenopausal women.

Effect of Circadian Rhythm on the Sedative Efficacy and Recovery Quality of Ciprofol General Anesthesia: A Multi-Center Observational Study

The goal of this multi-center observational study is to learn about the effect of circadian rhythm (morning vs. afternoon surgery) on the sedative efficacy, hemodynamic stability (especially induction-associated hypotension), and recovery quality of ciprofol general anesthesia in adult patients undergoing elective non-cardiac and non-cranial surgery, comparing target-controlled infusion (TCI) and non-TCI administration modes. The main question it aims to answer is: Does circadian rhythm (time of surgery: morning vs. afternoon) affect the sedative efficacy, incidence of induction-associated hypotension, and recovery quality of ciprofol general anesthesia? Eligible patients aged 18-65 years with ASA physical status I-II and BMI 18-30 kg/m² undergoing elective general anesthesia for non-cardiac and non-cranial surgery (duration 1-2 hours) will be grouped by anesthesia start time (morning: 08:00-11:00; afternoon: 14:00-17:00) and receive ciprofol induction and maintenance via TCI or non-TCI infusion. Perioperative data including hemodynamic changes, ciprofol dosage, recovery time, and adverse events will be recorded and analyzed.

Morning Bright Light Therapy and Daytime Functioning in University Students

This study tests whether a week of morning bright light therapy changes how well healthy young adults sleep and how alert, positive, and mentally sharp they feel during the day. Morning light is the body's main signal for keeping its internal clock and sleep-wake timing on track. Many university students keep irregular hours and spend most of the day indoors, where light is far dimmer than daylight. This study asks whether adding a short, bright morning light session can help. Each participant takes part for two weeks. For one week they use a bright light box for 30 minutes each morning, shortly after waking; for the other week they keep their usual lighting. The order of the two weeks is decided at random, and each person serves as their own comparison. Throughout both weeks, sleep is tracked with a wrist-worn Fitbit and a short daily diary. Participants also rate their sleepiness and mood, complete brief computer-based attention and memory tasks, and take part in a short interview at the end about their experience. The study compares the bright-light week with the usual-light week to see whether morning bright light improves sleep regularity and efficiency, reduces daytime sleepiness, lifts mood, or affects thinking performance. The trial is being conducted in waves; a first wave has completed and a second wave is planned, pending additional funding.

Effects of Afternoon Napping, Caffeine, and Standardised Active Recovery on Evening Athletic Performance

This study evaluated whether afternoon napping, caffeine ingestion, and a standardised active recovery and nutritional protocol could influence evening physical and cognitive performance in healthy university athletes. Participants completed five experimental conditions in a randomised crossover design: placebo without napping, napping with placebo, caffeine without napping, napping combined with caffeine, and napping combined with caffeine plus a standardised active recovery and nutritional protocol. The nap opportunity lasted 90 minutes and caffeine was administered at 5 mg/kg body mass. The main outcome was repeated agility performance. Additional outcomes included sprint performance, jumping performance, reaction time, subjective sleepiness, sleep characteristics during the nap opportunity, and selected physiological measures. The study also explored whether responses differed according to sex and chronotype.

Chronotype Alignment and Time Perception

People differ in chronotype - whether they function best in the morning ("larks") or the evening ("owls"). This study asks whether the match or mismatch between a person's chronotype and the time of day at which they are tested changes how they perceive time. Healthy morning-type and evening-type adults at three sites (Aarhus, Denmark; Changzhou, China; and Hong Kong) complete the same battery of perception and cognition tasks twice - once in the early morning (about 08:00) and once late in the evening (about 22:00), in counterbalanced order. The primary outcome is the accuracy (signed bias) of time-perception judgements; the key comparison is the interaction between chronotype and time of day (the "synchrony effect"). Secondary measures include timing precision, the subjective passage of time, sleepiness, mood, colour perception (with and without blue-blocking glasses) and perceptual decision-making. By testing the same protocol across three cultures and latitudes, the study examines whether circadian match/mismatch effects on temporal cognition generalise across populations.

Pistacho and Sleep Quality

The goal of this study is to evaluate the effect of pistachio (Pistacia vera L.) consumption on plasma melatonin, antioxidant capacity, and circadian rhythms in overweight young adults. The main question it aims to answer are: * Can the consumption of pistachios, specifically their content of compounds like phyto-melatonin, effectively regulate the human biological clock and circadian rhythms?

Exercise Interventions in Obstructive Sleep Apnea Syndrome

Obstructive Sleep Apnea Syndrome (OSA) is a condition characterized by repeated pauses or reductions in breathing during sleep, which can negatively affect sleep quality, daytime functioning, and physical capacity. Although regular exercise is known to have beneficial effects in OSA, the effects of different exercise approaches on circadian rhythm and functional capacity have not been sufficiently investigated.The primary aim of this study is to compare the effects of exercise snacking and aerobic exercise on circadian rhythm and functional capacity in individuals with OSA, in comparison with a control group. The secondary aim is to evaluate the effects of these exercise interventions on peripheral muscle strength, fatigue level, body composition, quality of life, and physical activity level.Participants will be randomly assigned to three groups: an aerobic exercise group, an exercise snacking group, and a control group. While the exercise groups will follow their respective intervention programs, the control group will continue their routine treatment.This study aims to answer whether exercise snacking, which consists of short bouts of exercise distributed throughout the day, may be an alternative or complementary approach to traditional aerobic exercise in individuals with OSA. In addition, this study aims to be the first randomized controlled trial evaluating the effects of exercise snacking on circadian rhythm and functional capacity in individuals with OSA.