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

Overview

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.

Interventions

• Dietary supplement Fisetin intervention
  Participants assigned to this intervention take capsules containing a fixed dose of Fisetin daily after breakfast.
• Dietary supplement Placebo
  Participants assigned to this intervention take a capsule containing 500 mg of corn starch daily after breakfast.
• Dietary supplement Urolithin A intervention
  Participants assigned to this intervention take capsules containing a fixed dose of Urolithin A daily after breakfast.

Primary outcome measures

• Subjective Sleep Quality Score [Time frame: From enrollment to the end of intervention at 12 weeks]
• Chronotype [Time frame: From enrollment to the end of intervention at 12 weeks]
• Polysomnography [Time frame: From enrollment to the end of intervention at 12 weeks]

Secondary outcome measures (12)

• Number of participants with abnormal blood and urine routine tests results [Time frame: From enrollment to the end of intervention at 12 weeks]
• Homeostatic Model Assessment of Insulin Resistance [Time frame: From enrollment to the end of intervention at 12 weeks]
• Frailty Assessment [Time frame: From enrollment to the end of intervention at 12 weeks]
• Fatigue Severity Scale Score [Time frame: From enrollment to the end of intervention at 12 weeks]
• Patient Health Questionnaire-9 Score [Time frame: From enrollment to the end of intervention at 12 weeks]
• Generalized Anxiety Disorder Scale Score [Time frame: From enrollment to the end of intervention at 12 weeks]
• Determination of Plasma Immunoglobulin Levels (g/L) [Time frame: From enrollment to the end of intervention at 12 weeks]
• DNA Methylation Clock [Time frame: From enrollment to the end of intervention at 12 weeks]
• Profile of Mood States-Short Form (Chinese Version) Score [Time frame: From enrollment to the end of intervention at 12 weeks]
• Plasma Interleukin Levels [Time frame: From enrollment to the end of intervention at 12 weeks]
• Gut Microbiota Diversity Analysis (Based on 16S rRNA Gene Sequencing) [Time frame: From enrollment to the end of intervention at 12 weeks]
• D-lactic acid level [Time frame: From enrollment to the end of intervention at 12 weeks]

Eligibility criteria

Inclusion criteria

• 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;

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Wuchang Hospital Affiliated to Wuhan University of Science and Technology — Wuhan

Identifiers

NCT: NCT06990256 · 2025-008-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗