Impact of Urolithin A (Mitopure) on Mitochondrial Quality in Muscle of Frail Older Adults (MitoEM)

The study is a single-center, randomized, placebo-control double-blind study in frail older adults over 65yrs. to investigate the impact of Mitopure (Urolithin A) supplementation on muscle mitochondrial quality in frail older adults after 8-weeks of supplementation

Study Overview

• Status: Completed
• Conditions: Frailty; Sarcopenia; Aging; Muscle Atrophy
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Mitopure (Urolithin A)

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Montréal, Canada
    • McGill University Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Frail (as defined by the Fried frailty criteria)nonsmoking participants in the age group of 65 to 85 years old, both male and female.
• A body mass index between 18 to 35 kg/m2.
• Not on any medications/living with medical conditions that would compromise the study outcome or the safety of the research participant.
• Able to participate and willing to give written informed consent and to comply with the study restrictions.
• Willing to be assigned randomly either to the UA or the control group.

Exclusion Criteria:

Participants must not have:

• Participated in a clinical trial within 90 days of screening or more than 4 times in the previous year.
• A history (within 3 months of screening) of alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 10 grams of alcohol).
• A history or presence of allergy to 5-aminolevulinic acid or porphyrins.
• A history or presence of allergy to lidocaine.
• Positive hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening.
• Unwillingness or inability to refrain from consuming alcohol within 48 hours before each visit until the end of said visit.
• Unwillingness or inability to refrain from consuming 8 or more units of xanthine containing beverages and foods per day during the entire study.
• Unwillingness to not consume other mitochondrial supplements during the course of the study (such as CoQ10, reseveratrol, NR, NMN etc.) and pomegranate juice
• unwillingness to not change diet or physical activity levels during the course of the study
• Unwillingness or inability to undergo a muscle biopsy.
• Underlying chronic disease, which in the opinion of the investigator, would interfere with study participation or the validity of the measurements.
• Unintentional weight loss ≤5% of regular body weight during the last 6 months.
• Medication requirements that may interfere with the interpretation of the results.
• Loss or donation of blood over 500mL three months prior (male subjects) or four months prior (female subjects) to participating in the study.
• Smoked (tobacco and/or marijuana mixed with tobacco (THC)) within 6 months prior to the start of the study;
• Abused drugs, medicine or alcohol within up to 30 days prior to the start of the study (Alcohol: more than 10 drinks a week, with more than 2 drinks a day most days; Drugs: THC, cocaine, opiates, amphetamines/methamphetamines, benzodiazepines, barbiturates, Buprenorphine, Creatin, Methadone metabolite, oxycodone, phencyclidine);
• A positive COVID-19 test taken 1 week to 24h before study start date.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Dietary supplement: Placebo; Placebo containing excipients other than Urolithin A (Mitopure)
Active Comparator: Mitopure (Urolithin A)	Dietary supplement: Mitopure (Urolithin A); UA is produced by the gut microbiome following the digestion of dietary precursors (polyphenols such as ellagitannins and punicalagins) present in fruits and nuts such as pomegranate, nuts and berries. In mouse models of aging and muscle dystrophy, UA was shown to induce mitophagy and mitochondrial function in the skeletal muscle. This was associated with improved muscle strength and endurance (Nat. Med, 2016; Sci Tran Med, 2021). In humans, UA was shown to be safe and bioavailable in multiple clinical studies (Nat. Met, 2019; Cell Rep Med, 2022; JAMA Network Open, 2022).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in mitochondrial area between placebo and active treated groups assessed via Electron Microscopy	8-weeks
Change in mitochondrial cristae density between placebo and active treated groups assessed via Electron Microscopy	8-weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
change between groups in mitochondrial calcium retention capacity measured by mitochondrial permeability transition pore (mPTP) sensitivity to calcium	8-weeks
mitochondrial DNA (mtDNA) over nuclear DNA ratio (mtDNA/nDNA) via qPCR	8-weeks
Changes in the timed up and go test (time needed to stand from an armchair, walk a distance of 3 meters, turn around and sit back down in the chair)	8-weeks
Changes in grip strength measured by a hand dynamometer	8-weeks
Changes in Berg balance test: Participant will be asked to maintain a given position or perform a task	8-weeks
Changes in distance walked during the six-minute walk test	8-weeks
Changes in the 30-second stand test: Participant will stand as many times as s/he can from a seated position for 30-seconds.	8-weeks
Changes in Four-square step test: To assess balance, participant will step over small sticks placed in an X on the floor	8-weeks
Changes in Unipedal stance test (UPST): First a ball will be kicked to determine dominant leg, then participant will be asked to stand on one leg (barefoot) with eyes open and again with eyes closed	8-weeks
Recording of adverse events	8-weeks
change between groups on the following: maximal mitochondrial O2 consumption assessed via via respirometry on permeabilized myofibers	8-weeks
Changes in body composition via Dual X-ray Absorptiometry (DXA) scan of total and appendicular lean mass	8-weeks
Changes in composition via Peripheral quantitative computed tomography (pQCT) of muscle tissue	8-weeks
Quantification of muscle fiber type (type I/II) via Myosin Heavy Chain immunolabeling	8-weeks
Analysis of markers of neuromuscular junction integrity (NCAM biomarker staining)	8-weeks
Changes in knee extension strength measured by a hand dynamometer	8-weeks

Collaborators and Investigators

• Sponsor: Amazentis SA
• Collaborators: McGill University Health Centre/Research Institute of the McGill University Health Centre; Université du Québec a Montréal
• Investigators: Principal Investigator: José Morais, McGill University Health Centre/Research Institute of the McGill University Health Centre; Principal Investigator: Gilles Gouspillou, PhD, UQAM (University of Quebec at Montreal)

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2024
• Primary Completion (Actual): April 25, 2025
• Study Completion (Actual): April 25, 2025

Study Registration Dates

• First Submitted: August 9, 2024
• First Submitted That Met QC Criteria: August 14, 2024
• First Posted (Actual): August 16, 2024

Study Record Updates

• Last Update Posted (Actual): May 28, 2025
• Last Update Submitted That Met QC Criteria: May 22, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Urolithin A; mitophagy
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neuromuscular Manifestations; Pathologic Processes; Pathological Conditions, Anatomical; Atrophy; Frailty; Sarcopenia; Muscular Atrophy
• Other Study ID Numbers: 2024-10182

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No