Studie Vlivu Urolithinu A na Populaci s BI vyšším neý 30 při výživové Restrikci
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Change in Appendicular Skeletal Muscle Index (ASMI) by Bioimpedance
研究概览
简要总结
Purpose. This study will test whether daily Urolithin A (500 mg) for 6 months helps adults with obesity lose weight while preserving functional muscle mass and improving markers of mitochondrial health, inflammation, and metabolism. All participants receive the same structured lifestyle program (nutrition and sleep guidance); half will receive Urolithin A and half a matching placebo.
Background. Weight loss can improve health but may also reduce skeletal muscle, especially in people with obesity. Aging and obesity are both linked to mitochondrial dysfunction, impaired autophagy/mitophagy, oxidative stress, and low-grade inflammation. Urolithin A is a gut-derived, diet-related compound that promotes mitophagy and may support muscle function and metabolic health.
Design. Single-center, randomized, placebo-controlled, parallel-group trial. About 100 adults aged 30-60 years with BMI >30 kg/m² and elevated visceral adiposity will be enrolled and randomized in a 1:1 ratio (stratified by sex and age ≤45 vs ≥45 years). Blinding will include participants, study staff, and assessors.
Intervention.
Urolithin A 500 mg orally once daily vs matching placebo, for 24 weeks.
A standardized lifestyle program for all participants: individualized energy restriction with higher protein intake, reduced carbohydrates, and time-restricted eating (11-hour eating window / 13-hour overnight fast); plus structured sleep-hygiene recommendations and light daily activity guidance.
No other dietary supplements are allowed during the study.
Main assessments. At baseline and regularly during the study, participants will undergo:
Body composition by bioimpedance (InBody), including skeletal muscle and visceral fat indices.
Muscle function (handgrip dynamometry; 30-second chair-stand).
Cardiometabolic and inflammatory biomarkers from blood (standard biochemistry, lipids, glucose/HbA1c, CRP; exploratory cytokines/adipokines).
Mitochondrial/aging biomarkers, including DNA-based epigenetic aging measures.
Cardiovascular/ANS function (heart-rate variability and vascular indices; MaxPulse Medicore).
Questionnaires on sleep quality, physical activity, and weight-management self-efficacy.
Visits and duration. 6-month participation with baseline, 3-weekly check-ins, and a final visit for repeat testing and blood sampling.
Outcomes. The study focuses on safety and on whether Urolithin A, compared with placebo, helps preserve functional muscle mass and improves mitochondrial, inflammatory, and metabolic biomarkers during weight loss.
Who can join. Adults 30-60 years with obesity and higher visceral fat who are willing to follow the lifestyle program. Key medical exclusions (e.g., diabetes, active autoimmune disease, pregnancy) and supplement restrictions apply; full criteria are provided in the Eligibility section.
Potential benefits and risks. Participants may benefit from weight loss support and close monitoring. Risks include blood draw discomfort and potential, usually mild, supplement-related side effects. Safety will be monitored throughout.
Location and sponsor. The study is conducted at Charles University, Faculty of Medicine in Hradec Králové (Czech Republic) under the Department of Preventive Medicine.
详细描述
Scientific Background and Rationale
Obesity and aging share pathophysiological features-mitochondrial dysfunction, impaired autophagy/mitophagy, oxidative stress, and chronic low-grade inflammation-that contribute to loss of skeletal muscle and functional capacity ("sarcopenic obesity") and increased frailty risk. While weight reduction improves cardiometabolic health, it can also decrease lean mass if not carefully managed.
Urolithin A (UA) is a bioactive metabolite derived from ellagitannins that has shown the ability to activate mitophagy, support mitochondrial function, and favor muscle health in preclinical and early clinical studies. We hypothesize that, when combined with a standardized lifestyle program, UA 500 mg/day will preserve functional muscle mass and favorable biomarker profiles during intentional weight loss in adults with obesity.
Objectives
Primary objective:
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
only those above
入排标准
- 年龄范围
- 30 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 30-60 years (inclusive) at screening
- •BMI > 30 kg/m² at screening
- •Visceral fat level ≥ 12 by segmental bioimpedance (InBody) at screening
- •Able and willing to follow the standardized lifestyle program (individualized energy restriction with higher protein, reduced carbohydrates, time-restricted eating 11:13) and sleep-hygiene guidance for 24 weeks
- •Willing to attend baseline and ~3-weekly follow-ups; undergo blood draws, bioimpedance, MaxPulse testing, and muscle strength/endurance tests; and complete questionnaires (WEL, PSQI, GPAQ)
- •Medication stability: chronic medications (e.g., treated hypertension, antidepressants) stable for ≥3 months before baseline; only clinically necessary changes allowed during the study
- •Permitted conditions/therapies (if stable): common allergies/atopic eczema; food intolerances; contraception and menopausal hormone therapy
- •Women of childbearing potential: negative pregnancy test at baseline; agreement to use highly effective contraception during the study and for 4 weeks after last dose; not breastfeeding
- •Able to provide written informed consent
排除标准
- •Known thyroid disease (untreated/unstable hypothyroidism or hyperthyroidism)
- •Type 2 diabetes mellitus (diagnosed or on glucose-lowering therapy)
- •Autoimmune disease, including psoriasis
- •Inflammatory bowel disease or other chronic inflammatory GI disorders (e.g., Crohn's disease, celiac disease)
- •Dyslipidemia treated with statins
- •Pregnancy, lactation, or planned pregnancy during the study period
- •Active malignant disease
- •Cognitive impairment or neurodegenerative disease that may affect consent or adherence
- •Severe psychiatric disorder that would preclude participation (e.g., severe major depression) or unstable depression/medication changes within the past 3 months
- •Uncontrolled comorbidity or decompensated chronic disease (e.g., uncontrolled hypertension; systolic ≥175 mmHg at screening)
- •Severe or limiting musculoskeletal condition preventing participation in assessments or the lifestyle program
- •Use of non-study dietary supplements (vitamins, herbal/nutraceutical products) that the participant is unwilling or unable to discontinue from baseline through end of study
- •Known allergy/intolerance to Urolithin A or capsule excipients
- •Any condition that, in the investigator's judgment, makes participation unsafe or could compromise data integrity
研究组 & 干预措施
Placebo
干预措施: Placebo (Other)
Urolithin A
干预措施: Urolithin A 500mg (Dietary Supplement)
结局指标
主要结局
Change in Appendicular Skeletal Muscle Index (ASMI) by Bioimpedance
时间窗: Baseline to Week 24 (end of intervention)
ASMI = sum of lean mass in both arms and legs (kg) divided by height² (m²), derived from segmental bioimpedance (InBody). Primary comparison is change from baseline to Week 24 between Urolithin A and placebo using ANCOVA adjusting for baseline, sex, and age stratum. Higher ASMI reflects greater functional muscle mass.
次要结局
- LDL-C(Baseline to Week 24)
- Inflammation (suPAR)(Baseline to Week 24)
- Change in Handgrip Strength (kg)(Baseline to Week 24)
- Change in Visceral Adipose Area (cm²) by Bioimpedance(Baseline to Week 24)
- Change in Percent Body Fat (%)(Baseline to Week 24)
- Glycemic Control (HbA1c)(Baseline to Week 24)
- GDF15(Baseline to Week 24)
- Autonomic/Vascular Function (Arterial Elasticity)(Baseline to Week 24)
- Epigenetic Aging Panel (DNA Methylation Age Acceleration)(Baseline to Week 24)
- Weight-Loss Responder Rates (≥5% and ≥10% Body Weight)(Baseline to Week 24)
- Patient-Reported Outcomes Panel (WEL)(Baseline to Week 24)
- Patient-Reported Outcomes Panel (PSQI)(Baseline to Week 24)
- Patient-Reported Outcomes Panel (GPAQ)(Baseline to week 24)
- Safety Panel (TEAEs and SAEs)(From first dose to Week 24)
研究者
Pavel Borsky
Principal Investigator
Charles University, Czech Republic