Clinical trial NCT06556706: Impact of Urolithin A (Mitopure) on Mitochondrial Quality in Muscle of Frail Older Adults
Official title: Impact of Urolithin A (Mitopure) on Mitochondrial Quality in Muscle of Frail Older Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Frailty
Sarcopenia
Aging
Muscle Atrophy
Keywords: mitophagy
Urolithin A
Lead sponsor: Amazentis SA
Sponsor class: INDUSTRY
Collaborators: name: Université du Québec a Montréal
name: McGill University Health Centre/Research Institute of the McGill University Health Centre
First posted: 2024-08-16
Enrollment: 26
Sex: ALL
Minimum age (years): 65
Maximum age (years): 85
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: Change in mitochondrial area between placebo and active treated groups assessed via Electron Microscopy
timeFrame: 8-weeks
measure: Change in mitochondrial cristae density between placebo and active treated groups assessed via Electron Microscopy
timeFrame: 8-weeks
Secondary outcomes:
measure: change between groups on the following: maximal mitochondrial O2 consumption assessed via via respirometry on permeabilized myofibers
timeFrame: 8-weeks
measure: change between groups in mitochondrial calcium retention capacity measured by mitochondrial permeability transition pore (mPTP) sensitivity to calcium
timeFrame: 8-weeks
measure: mitochondrial DNA (mtDNA) over nuclear DNA ratio (mtDNA/nDNA) via qPCR
timeFrame: 8-weeks
measure: Changes in body composition via Dual X-ray Absorptiometry (DXA) scan of total and appendicular lean mass
timeFrame: 8-weeks
measure: Changes in composition via Peripheral quantitative computed tomography (pQCT) of muscle tissue
timeFrame: 8-weeks
measure: 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)
timeFrame: 8-weeks
measure: Changes in grip strength measured by a hand dynamometer
timeFrame: 8-weeks
measure: Changes in Berg balance test: Participant will be asked to maintain a given position or perform a task
timeFrame: 8-weeks
measure: Changes in distance walked during the six-minute walk test
timeFrame: 8-weeks
measure: Changes in the 30-second stand test: Participant will stand as many times as s/he can from a seated position for 30-seconds.
timeFrame: 8-weeks
measure: Changes in Four-square step test: To assess balance, participant will step over small sticks placed in an X on the floor
timeFrame: 8-weeks
measure: 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
timeFrame: 8-weeks
measure: Recording of adverse events
timeFrame: 8-weeks
measure: Quantification of muscle fiber type (type I/II) via Myosin Heavy Chain immunolabeling
timeFrame: 8-weeks
measure: Analysis of markers of neuromuscular junction integrity (NCAM biomarker staining)
timeFrame: 8-weeks
measure: Changes in knee extension strength measured by a hand dynamometer
timeFrame: 8-weeks
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: McGill University Health Center
Study officials:
affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
name: José Morais
role: PRINCIPAL_INVESTIGATOR
affiliation: UQAM (University of Quebec at Montreal)
name: Gilles Gouspillou, PhD
role: PRINCIPAL_INVESTIGATOR
References: