Urolithin A Supplementation in Middle-aged Adults With Obesity

Study Overview
=================
Brief Summary
-----------------
The goal of this clinical trial is to learn about the effect of urolithin A, a dietary supplement, on blood flow in middle-aged adults with obesity. The main question it aims to answer is: - Does urolithin A supplementation improve blood flow in large and small blood vessels in middle-aged adults with obesity? Participants will be asked to: Take the dietary supplement daily for 4 weeks Attend two study visits to have their blood vessels checked, answer questionnaires, and give a sample of blood Researchers will compare people who took the dietary supplement with others who took a placebo to see if the blood flow in the blood vessels improved.

Detailed Description
-----------------
This study aims to measure the effect of urolithin A supplementation on endothelial function, cerebral blood flow regulation, and serum biomarkers of NO bioavailability and mitochondrial function in middle-aged adults with obesity. Briefly, 54 adults aged 40-64 years of age with a body mass index equal to or greater than 30 kg/m2 will be recruited to participate in a double-blind placebo-controlled parallel study for 4 weeks. Participants will be randomly assigned to intervention or control group. Those in the intervention group will consume 1,000 mg of urolithin A daily in the form of softgel capsules, whereas those in the control group will consume a placebo. Data collection will occur at baseline (day 0) and endpoint (day 28). The investigators will compare outcomes between control and intervention group. Researchers expect that urolithin A supplementation in middle-aged adults with obesity improves endothelial function and cerebral blood flow regulation, and that this improvement is accompanied by changes in biomarkers of NO bioavailability and mitochondrial function.

Official Title
-----------------
Urolithin A Supplementation to Improve Endothelial and Cerebrovascular Function in Middle-aged Adults With Obesity

Conditions
-----------------
Obesity, Vascular Dementia, Cognitive Impairment

Intervention / Treatment
-----------------
* Dietary Supplement: Urolithin A
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age: 40-64 years old, inclusive Obesity [BMI ≥30 kg/m2] Ability to read, write, and speak English Competence to provide written informed consent Exclusion Criteria: Pregnant or breastfeeding women, or women who intend to become pregnant within the study period History of hypertension History of type 1 or type 2 diabetes mellitus Significant cardiac disease or chest pain in the last 6 months History of depression or anxiety History of cognitive impairment History of significant GI disease (e.g., IBS, Crohn's disease) Allergy or intolerance to one or more of the intervention components Undergoing treatment for active cancer History of neurodegenerative disorders (e.g., multiple sclerosis) Presence of any condition affecting swallowing ability Any other medical condition that the investigators deem would adversely affect the participant's safety or ability to complete the study

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 64 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br> | Dietary Supplement: Urolithin A<br>* Participants in the intervention group will receive 500 mg of urolithin A twice daily for 4 weeks (1,000 mg daily in total). The supplement will be administered in the form of softgels (4 softgels daily).<br>|
| Placebo Comparator: Control<br> | Other: Placebo<br>* Participants in the control group will receive 0 mg of urolithin A twice daily for 4 weeks. The placebo will be administered in the form of inactive capsules (4 capsules daily).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in arterial function and local stiffness | Flow-mediated dilation | Baseline (day 0) and endpoint (day 28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in blood flow on the surface of the hand | Laser speckle contrast imaging | Baseline (day 0) and endpoint (day 28) | 
| Change in homeostatic cerebral blood flow | Functional near-infrared spectroscopy | Baseline (day 0) and endpoint (day 28) | 
| Change in plasma biomarkers of NO homeostasis | Asymmetrical dimethylarginine | Baseline (day 0) and endpoint (day 28) | 
| Change in plasma biomarkers of NO homeostasis | Endothelin-1 | Baseline (day 0) and endpoint (day 28) | 
| Change in plasma biomarkers of NO homeostasis | Bioactive nitrogen oxides | Baseline (day 0) and endpoint (day 28) | 
| Change in plasma biomarkers of mitochondrial function | Acylcarnitines | Baseline (day 0) and endpoint (day 28) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Obesity, Urolithin A, Middle aged, Flow-mediated dilation, Endothelial function, fNIRS, Nitric oxide, Vascular contributions to cognitive impairment and dementia