Urolithin A Supplementation to Boost Immune Health

Study Overview
=================
Brief Summary
-----------------
To show that a natural mitophagy activator (Urolithin A) given orally can modulate mitochondrial activity in immune cells in healthy adults and this results in better immune function

Official Title
-----------------
Impact of Urolithin A Supplementation on Mitochondrial Health of Immune Cells (MitoImmune): a Randomized Trial

Conditions
-----------------
Aging

Intervention / Treatment
-----------------
* Dietary Supplement: Softgel containing placebo
* Dietary Supplement: Softgel containing 250mg of Urolithin A (Mitopure)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy Adults that do not suffer from an uncontrolled chronic medical condition that carries metabolic consequences (as assessed by the study physician) BMI<35kg/m2 Provide informed consent Adults aged 45-70 years, both genders Subjects who have not received any systemic immunosuppression in the past 6 months Subjects with any medical condition that in the opinion of the investigators would compromise the study outcome or the safety of the research participant Exclusion Criteria: Subject has any concurrent medical, orthopedic, or psychiatric condition that, in the opinion of the Investigator, would compromise his/her ability to comply with the study requirements; Clinically significant abnormal laboratory results at screening Participation in a clinical research trial within 30 days prior to randomization Allergy or sensitivity to study ingredients Individuals who are cognitively impaired and/or who are unable to give informed consent Any condition which in the Investigator's opinion may adversely affect the subject's ability to complete the study or its measures or which may pose significant risk to the subject Current gastrointestinal condition which could interfere with the study (e.g. IBS/IBD, diarrhea, acid reflux disease, dysphagia etc.); Excessive alcohol consumption and/or a smoker Concomitant use of statins Engage in regular moderate or vigorous physically activities (i.e. Category 3 as per the IPAQ activity classification) Concomitant use of corticosteroids, antibiotics, any anabolic steroid, creatine, whey protein supplements, casein or branched-chain amino acids (BCAAs), immune-boosting(Vitamin C, Zinc) or mitochondrial (COQ10, NAD+) supplements within 45 days prior to screening

Ages Eligible for Study
-----------------
Minimum Age: 45 Years
Maximum Age: 70 Years

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

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Dietary Supplement: Softgel containing placebo<br>* Single oral dose administration (4 softgels) to be orally administered daily according to the randomization for 28 days<br>|
| Active Comparator: Urolithin A (Mitopure)<br> | Dietary Supplement: Softgel containing 250mg of Urolithin A (Mitopure)<br>* Single oral dose administration (4 softgels) to be orally administered daily according to the randomization for 28 days<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in percentages of CD3+ T-cell immune cell population | In particular, number of CD8+ T memory stem cells (identified by expression of CD8+CD45RA+CCR7+CD95+) and naïve-like T cells (CD8+CD45RA+CCR7+CD95-) | 28 days | 
| Change in Mitochondrial activity in CD3+ T-cells | Mitochondrial function evaluated as OXPHOS activity via ELISA /Seahorse | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pro and anti-inflammatory cytokine levels (IL-6, TNF-a, IL1-B, IL-10) in plasma and/or ex-vivo antigenic stimulation |  | 28 days | 
| Change in percentages of other immune cell populations (B cells, NK cells, Macrophages, DCs etc.) via flow cytometry |  | 28 days | 
| Change in Mitochondrial content on CD3 T-cell populations via Mitotracker staining using flow cytometry |  | 28 days | 
| Change in gene-expression: single cell analysis of CD3+ T-cells |  | 28 days | 
| Change in PBMC's immune function assessment (mixed-leukocyte reaction (MLR) via antigenic stimulation |  | 28 days | 
| Change in Lipid profile |  | 28 days | 
| Epigenetic age of PBMCs (DNA Methylation-derived epigenetic age) |  | 28 days | 
| Number of adverse events |  | 28 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Immune system, mitochondria