Clinical trial NCT06990256: Evaluation of Urolithin A and Fisetin on Improving Sleep and Aging Biomarkers
Official title: Evaluation of Urolithin A and Fisetin on Improving Sleep and Aging Biomarkers in Middle-Aged and Older Adults: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Sleep Disorder
Aging
Keywords: Urolithin A
Fisetin
Sleep Disorder
Aging
Lead sponsor: Huazhong University of Science and Technology
Sponsor class: OTHER
Collaborators: name: Wuhan Wuchang Hospital
name: Abinopharm, Inc
First posted: 2025-05-25
Enrollment: 80
Sex: ALL
Minimum age (years): 45
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Aged 45-70 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;

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Subjective Sleep Quality Score
timeFrame: From enrollment to the end of intervention at 12 weeks
measure: Chronotype
timeFrame: From enrollment to the end of intervention at 12 weeks
measure: Daytime Function
timeFrame: From enrollment to the end of intervention at 12 weeks
measure: Actigraphy dairy
timeFrame: From enrollment to the end of intervention at 12 weeks
measure: Polysomnography
timeFrame: From enrollment to the end of intervention at 12 weeks
Secondary outcomes:
measure: Number of participants with abnormal blood and urine routine tests results
timeFrame: From enrollment to the end of intervention at 12 weeks
measure: Homeostatic Model Assessment of Insulin Resistance
timeFrame: From enrollment to the end of intervention at 12 weeks
measure: Frailty Assessment
timeFrame: From enrollment to the end of intervention at 12 weeks
measure: Fatigue Severity Scale Score
timeFrame: From enrollment to the end of intervention at 12 weeks
measure: Patient Health Questionnaire-9 Score
timeFrame: From enrollment to the end of intervention at 12 weeks
measure: Generalized Anxiety Disorder Scale Score
timeFrame: From enrollment to the end of intervention at 12 weeks
measure: Determination of Plasma Immunoglobulin Levels (g/L)
timeFrame: From enrollment to the end of intervention at 12 weeks
measure: Lipofuscin Measurement
timeFrame: From enrollment to the end of intervention at 12 weeks
measure: DNA Methylation Clock
timeFrame: From enrollment to the end of intervention at 12 weeks
measure: Profile of Mood States-Short Form (Chinese Version) Score
timeFrame: From enrollment to the end of intervention at 12 weeks
measure: Plasma Interleukin Levels
timeFrame: From enrollment to the end of intervention at 12 weeks
measure: Cortisol Measurement
timeFrame: From enrollment to the end of intervention at 12 weeks
measure: Gut Microbiota Diversity Analysis (Based on 16S rRNA Gene Sequencing)
timeFrame: From enrollment to the end of intervention at 12 weeks
measure: D-lactic acid level
timeFrame: From enrollment to the end of intervention at 12 weeks
measure: NAD+ Level Measurement
timeFrame: From enrollment to the end of intervention at 12 weeks
measure: Quality of Life Assessment
timeFrame: From enrollment to the end of intervention at 12 weeks
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Wuchang Hospital Affiliated to Wuhan University of Science and Technology
state: Hubei
Study officials:
References: