Evaluation of Urolithin A and Fisetin on Improving Sleep and Aging Biomarkers in Middle-Aged and Older Adults: A Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 83
- 试验地点
- 1
- 主要终点
- Chronotype
研究概览
简要总结
The goal of this clinical trial is to evaluate the effects of Urolithin A (UA) and Fisetin on improving sleep and aging biomarkers in middle-aged and older adults. The main questions it aims to answer are:
Can UA and Fisetin improve sleep quality in middle-aged and older adults? Do these substances have a positive effect on aging biomarkers, such as inflammation, oxidative stress, and aging-related proteins? Researchers will compare four groups: Placebo group (a look-alike substance that contains no drug), 500 mg UA group, 500 mg Fisetin group and 300 mg UA + 200 mg Fisetin group.
Participants will:
Take the assigned capsules daily after breakfast for 12 weeks. Attend three clinic visits (baseline [Week 0], mid-intervention [Week 4], and post-intervention [Week 12]) including blood tests, sleep quality assessments (PSQI scale, actigraphy, polysomnography), and analysis of aging biomarkers (DNA methylation, inflammatory cytokines, etc.). Keep a sleep diary, complete a dietary survey, assess mental health, and measure frailty indicators. Provide stool and urine samples at baseline and post-intervention for gut microbiome and metabolite analysis. This trial aims to provide scientific evidence for the development of new nutritional intervention strategies to improve the healthy aging.
详细描述
The accelerating population aging has exacerbated the burden of chronic diseases among middle-aged and older adults, with sleep disorders emerging as a core health issue that forms a vicious cycle with aging. Urolithin A and Fisetin as dietary bioactive components have gained attention for their potential health benefits, including anti-aging, anti-inflammatory, and antioxidant properties. However, researches on their effects in sleep and aging remain limited, and clinical evidence for their combined intervention is currently lacking. This study aims to evaluate the effects of Urolithin A and Fisetin on improving sleep and aging biomarkers in middle-aged and older adults, providing scientific evidence for developing new scientific dietary strategies. It is a randomized controlled trial. A total of 80 participants will be recruited and randomly assigned to four groups: control group, Urolithin A 500 mg group, Fisetin 500 mg group, and Urolithin A 300 mg + Fisetin 200 mg group. The intervention period will last 12 weeks, with all participants taking one capsule of the intervention substance or placebo daily after breakfast. Primary outcomes include subjective and objective sleep quality assessments and frailty assessment. Secondary outcomes include metabolic, immune and inflammatory markers, gut microbiota analysis and quality of life assessment. Participants will undergo three follow-up assessments: baseline (week 0), mid-intervention (week 4), and end of intervention (week 12). Data will be analyzed using SAS 9.4 following the intention-to-treat principle. It is expected to provide preliminary data on the single and combined effects of Urolithin A and Fisetin on improving sleep and aging biomarkers in middle-aged and older adults, as well as reveal their potential synergistic effects. The rigorous and innovative design will serve as a reference for future mechanistic studies, which has important public health significance.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 30 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 30-75 years;
- •Total score > 5 points on the Pittsburgh Sleep Quality Index (PSQI) for sleep quality assessment;
- •Able to use personal mobile devices for WeChat, internet access, and related operations;
- •Informed about the intervention trial and willing to undergo sleep monitoring and other examinations during the study;
- •Commitment to consume coffee, strong tea, or alcohol ≤1 time per week during the trial period;
排除标准
- •Participation in any clinical trials or dietary/exercise intervention programs within the past 3 months or concurrently;
- •Diagnosis of major mental disorders or family history thereof, or current use of psychotropic drugs or mood-regulating medications;
- •Experiencing major psychological trauma (e.g., death of a close relative, significant financial loss) personally or within the family in the past 3 months;
- •Severe diseases affecting inflammatory levels and/or endocrine components (e.g., severe obesity, uncontrolled diabetes or poorly controlled blood glucose, myocardial infarction, cerebral infarction);
- •Current use of hormonal medications, beta-blockers, steroids, non-steroidal anti-inflammatory drugs (NSAIDs), etc.;
- •Use of medications potentially affecting sleep or aging biomarkers (e.g., melatonin, antidepressants, anxiolytics) within the past 3 months;
- •Plans for relocation or long-term travel within the next 6 months, which may hinder continuous intervention and follow-up.
研究组 & 干预措施
Placebo Control group
Take a placebo capsule (containing 500 mg of corn starch) once daily after breakfast for a total of 12 weeks.
干预措施: Placebo (Dietary Supplement)
Urolithin A Treatment Group
Take a intervention capsule (containing 500 mg of Urolithin A) once daily after breakfast for a total of 12 weeks.
干预措施: Urolithin A intervention (Dietary Supplement)
Fisetin Treatment Group
Take a intervention capsule (containing 500 mg of Fisetin) once daily after breakfast for a total of 12 weeks.
干预措施: Fisetin intervention (Dietary Supplement)
Combined Urolithin A and Fisetin Treatment Group
Take a intervention capsule (containing 300 mg of Urolithin A + 200 mg of Fisetin) once daily after breakfast for a total of 12 weeks.
干预措施: Fisetin intervention (Dietary Supplement)
Combined Urolithin A and Fisetin Treatment Group
Take a intervention capsule (containing 300 mg of Urolithin A + 200 mg of Fisetin) once daily after breakfast for a total of 12 weeks.
干预措施: Urolithin A intervention (Dietary Supplement)
结局指标
主要结局
Chronotype
时间窗: From enrollment to the end of intervention at 12 weeks
Chronotype will be evaluated using the Morningness-Eveningness Questionnaire (MEQ), a self-reported scale consisting of 19 items assessing physiological and behavioral preferences across a 24-hour cycle. MEQ-5 will be used in this trial, which scores range from 4 to 25, with higher scores indicating a morning-oriented chronotype and lower scores reflecting an evening-oriented preference.
Polysomnography
时间窗: From enrollment to the end of intervention at 12 weeks
Polysomnography (PSG) is a comprehensive sleep assessment and the reference standard for objectively evaluating sleep physiology and sleep disorders. It records multiple signals during sleep, typically including electroencephalography, electrooculography, and electromyography, as well as respiratory airflow and effort, oxygen saturation, electrocardiography, and body position/limb movements, to characterize sleep stages, sleep architecture, and sleep-related events. PSG is commonly used to assess sleep-disordered breathing (e.g., obstructive sleep apnea), periodic limb movement disorder, and REM sleep behavior disorder. All PSG data in this study will be scored and analyzed according to American Academy of Sleep Medicine (AASM) guidelines.
Subjective Sleep Quality Score
时间窗: From enrollment to the end of intervention at 12 weeks
Sleep quality will be assessed using the Pittsburgh Sleep Quality Index (PSQI), developed by psychiatrist Dr. Buysse in 1989. The PSQI includes seven components: subjective sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbance, used sleep medication, and daytime dysfunction. Each component score ranges from 0 to 3, with a total score ranges from 0 to 21. Higher scores indicate poorer sleep quality, and a total score \>7 suggests clinically significant sleep impairment.
次要结局
- Arterial stiffness assessment(From enrollment to the end of intervention at 12 weeks)
- Cardiopulmonary exercise testing(From enrollment to the end of intervention at 12 weeks)
- Profile of Mood States-Short Form (Chinese Version) Score(From enrollment to the end of intervention at 12 weeks)
- Number of participants with abnormal blood and urine routine tests results(From enrollment to the end of intervention at 12 weeks)
- Homeostatic Model Assessment of Insulin Resistance(From enrollment to the end of intervention at 12 weeks)
- Frailty Assessment(From enrollment to the end of intervention at 12 weeks)
- Fatigue Severity Scale Score(From enrollment to the end of intervention at 12 weeks)
- Patient Health Questionnaire-9 Score(From enrollment to the end of intervention at 12 weeks)
- Generalized Anxiety Disorder Scale Score(From enrollment to the end of intervention at 12 weeks)
- Determination of Plasma Immunoglobulin Levels (g/L)(From enrollment to the end of intervention at 12 weeks)
- DNA Methylation Clock(From enrollment to the end of intervention at 12 weeks)
- Plasma Interleukin Levels(From enrollment to the end of intervention at 12 weeks)
- Gut Microbiota Diversity Analysis (Based on 16S rRNA Gene Sequencing)(From enrollment to the end of intervention at 12 weeks)
- D-lactic acid level(From enrollment to the end of intervention at 12 weeks)
- NAD+ Level Measurement(From enrollment to the end of intervention at 12 weeks)
- Quality of Life Assessment(From enrollment to the end of intervention at 12 weeks)
研究者
Liangkai Chen
Associate professor
Huazhong University of Science and Technology