Mitopure for Frailty
(MitoEM Trial)
Recruiting in Palo Alto (17 mi)
Age: 65+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Amazentis SA
Disqualifiers: Chronic disease, Drug abuse, Alcohol abuse, others
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?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
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but it mentions that medication requirements that may interfere with the study results could be a concern. It's best to discuss your specific medications with the study team to see if they might affect your participation.
What evidence supports the effectiveness of the treatment Mitopure (Urolithin A) for frailty?
Research shows that Urolithin A, the active ingredient in Mitopure, can improve muscle health and mitochondrial function, which are important for reducing frailty. Clinical trials in elderly people have demonstrated that Urolithin A is safe and can enhance cellular health, potentially slowing aging and improving quality of life.
12345Is Mitopure (Urolithin A) safe for human use?
Urolithin A, also known as Mitopure, has been shown to be safe in humans, with a favorable safety profile observed in clinical trials. It has been tested at doses up to 2,500 mg/day and is considered safe, with studies indicating it can improve mitochondrial health in elderly individuals.
12345How does the drug Mitopure (Urolithin A) differ from other treatments for frailty?
Mitopure (Urolithin A) is unique because it enhances cellular health by promoting mitophagy (the process of removing damaged mitochondria) and improving mitochondrial function, which is crucial for muscle health and reducing inflammation. Unlike other treatments, it is a natural compound derived from foods like pomegranates and has shown potential in improving muscle function and preventing age-related decline in clinical studies.
12356Eligibility Criteria
This trial is for frail older adults over the age of 65 who are experiencing muscle weakness or wasting. Participants should be interested in testing a supplement that might improve muscle health.Inclusion Criteria
I am between 65-85 years old, do not smoke, and am considered frail.
A body mass index between 18 to 35 kg/m2
I am not on any medication or have conditions that could affect the study's safety or results.
+2 more
Exclusion Criteria
I have not lost or donated more than 500mL of blood in the past 3 months (if male) or 4 months (if female).
I am not willing or able to have a muscle biopsy.
I agree not to take any mitochondrial supplements or drink pomegranate juice during the study.
+14 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive Mitopure (Urolithin A) or placebo for 8 weeks
8 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests Mitopure (Urolithin A) to see if it can enhance mitochondrial quality in muscles after 8 weeks. It's a controlled test where some get Mitopure and others get a placebo, without knowing which one they receive.
2Treatment groups
Active Control
Placebo Group
Group I: Mitopure (Urolithin A)Active Control1 Intervention
Group II: PlaceboPlacebo Group1 Intervention
Mitopure (Urolithin A) is already approved in United States for the following indications:
🇺🇸 Approved in United States as Mitopure for:
- Generally Recognized as Safe (GRAS) for dietary supplement use
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
McGill University Health CenterMontréal, Canada
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Who Is Running the Clinical Trial?
Amazentis SALead Sponsor
Université du Québec a MontréalCollaborator
McGill University Health Centre/Research Institute of the McGill University Health CentreCollaborator
References
Impact of the Natural Compound Urolithin A on Health, Disease, and Aging. [2021]Urolithin A (UA) is a natural compound produced by gut bacteria from ingested ellagitannins (ETs) and ellagic acid (EA), complex polyphenols abundant in foods such as pomegranate, berries, and nuts. UA was discovered 40 years ago, but only recently has its impact on aging and disease been explored. UA enhances cellular health by increasing mitophagy and mitochondrial function and reducing detrimental inflammation. Several preclinical studies show how UA protects against aging and age-related conditions affecting muscle, brain, joints, and other organs. In humans, benefits of UA supplementation in the muscle are supported by recent clinical trials in elderly people. Here, we review the state of the art of UA's biology and its translational potential as a nutritional intervention in humans.
Urolithin A prevents streptozotocin-induced diabetic cardiomyopathy in rats by activating SIRT1. [2022]This study examined the cardiac anti-cardiomyopathy (DC) protective effect of urolithin A in streptozotocin (STZ)-treated rats and investigated if this protection involves activation of SIRT1 signaling. Diabetes was induced first STZ (65 mg/kg, i.p.) before starting the experiments. Adult male rats (n = 8/group) were treated for 8 weeks as control (non-diabetic), control + urolithin A (2.5 mg/kg/i.p.), STZ, STZ + urolithin A, and STZ + urolithin A + Ex-527 (1 mg/kg/i.p.) (a SIRT1 inhibitor). With no effect on fasting glucose and insulin levels, urolithin A improved left ventricular (LV) function and structure and reduced heart weight and serum levels of cardiac markers in STZ-treated rats. Also, it prevented collagen deposition, reduced mRNA levels of Bax, cleaved caspaspe3, collagen 1A1, transforming growth factor-β1 (TGF-β1), and Smad3 but enhanced those of Bcl2 in the LVs of diabetic rats. However, urolithin A suppressed the generation of reactive oxygen species (ROS), activated the nuclear factor erythroid 2-related factor 2 (Nrf2), and increased the levels of manganese superoxide dismutase (MnSOD) and total glutathione (GSH) in the LVs of the non-diabetic and diabetic rats, In parallel, it suppressed the cardiac activity of NF-nuclear factor-kappa beta p65 (κB p65) and reduced levels of tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Coincided with these events, urolithin A promoted higher activity, mRNA, and total/nuclear protein levels of SIRT1 and lowered the levels of acetyl-FOXO1, Nrf2, NF-κB, and p53. All these benefits of urolithin A were prevented by Ex-527. In conclusion, urolithin A protects against DC by activating SIRT signaling.
Urolithin A as a Potential Agent for Prevention of Age-Related Disease: A Scoping Review. [2023]The aging of an organism is hallmarked by systemic loss of functional tissue, resulting in increased fragility and eventual development of age-related neurodegenerative, musculoskeletal, cardiovascular, and neoplastic diseases. Growing scientific evidence points to mitochondrial dysfunction as a key contributor in the aging process and subsequent development of age-related pathologies. Under normal physiologic conditions, the body removes dysfunctional mitochondria via an autophagic process known as mitophagy. Urolithin A (UA), a metabolite produced when gut microflora digests the polyphenol compounds ellagitannin and ellagic acid, is a known inducer of mitophagy via several identified mechanisms of action. The primary objective of this scoping review is to identify and summarize the clinical relevance of UA supplementation in the prevention of age-related pathology and diseases. A computer-assisted literature review was performed using PubMed and EMBASE for primary source research articles examining UA supplementation and aging-related pathologies. A total of 293 articles were initially identified from a database search, and 15 articles remained for inclusion in this review, based on predetermined criteria. Analysis of the 15 identified publications demonstrated that UA holds potential as a dietary intervention for slowing the progression of aging and preventing the development of age-related disease. This review also illustrates the potential role that mitochondrial health and inflammation play in the progression of age-related pathology. Identifying the clinical relevance of UA supplementation in the prevention of age-related pathology and diseases will help further the focus of research on treatments that may improve the longevity and quality of life in patients at risk for these comorbidities.
A mechanistic insight into the biological activities of urolithins as gut microbial metabolites of ellagitannins. [2022]Urolithins are the gut metabolites produced from ellagitannin-rich foods such as pomegranates, tea, walnuts, as well as strawberries, raspberries, blackberries, and cloudberries. Urolithins are of growing interest due to their various biological activities including cardiovascular protection, anti-inflammatory activity, anticancer properties, antidiabetic activity, and antiaging properties. Several studies mostly based on in vitro and in vivo experiments have investigated the potential mechanisms of urolithins which support the beneficial effects of urolithins in the treatment of several diseases such as Alzheimer's disease, type 2 diabetes mellitus, liver disease, cardiovascular disease, and various cancers. It is now obvious that urolithins can involve several cellular mechanisms including inhibition of MDM2-p53 interaction, modulation of mitogen-activated protein kinase pathway, and suppressing nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity. Antiaging activity is the most appealing and probably the most important property of urolithin A that has been investigated in depth in recent studies, owing to its unique effects on activation of mitophagy and mitochondrial biogenesis. A recent clinical trial showed that urolithin A is safe up to 2,500 mg/day and can improve mitochondrial biomarkers in elderly patients. Regarding the importance of mitochondria in the pathophysiology of many diseases, urolithins merit further research especially in clinical trials to unravel more aspects of their clinical significance. Besides the nutritional value of urolithins, recent studies proved that urolithins can be used as pharmacological agents to prevent or cure several diseases. Here, we comprehensively review the potential role of urolithins as new therapeutic agents with a special focus on the molecular pathways that have been involved in their biological effects. The pharmacokinetics of urolithins is also included.
The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. [2021]Urolithin A (UA) is a natural dietary, microflora-derived metabolite shown to stimulate mitophagy and improve muscle health in old animals and in preclinical models of aging1. Here, we report the results of a first-in-human clinical trial in which we administered UA, either as a single dose or as multiple doses over a 4-week period, to healthy, sedentary elderly individuals. We show that UA has a favourable safety profile (primary outcome). UA was bioavailable in plasma at all doses tested, and 4 weeks of treatment with UA at doses of 500 mg and 1,000 mg modulated plasma acylcarnitines and skeletal muscle mitochondrial gene expression in elderly individuals (secondary outcomes). These observed effects on mitochondrial biomarkers show that UA induces a molecular signature of improved mitochondrial and cellular health following regular oral consumption in humans.
Mitophagy Activation by Urolithin A to Target Muscle Aging. [2023]The age-related loss of skeletal muscle function starts from midlife and if left unaddressed can lead to an impaired quality of life. A growing body of evidence indicates that mitochondrial dysfunction is causally involved with muscle aging. Muscles are tissues with high metabolic requirements, and contain rich mitochondria supply to support their continual energy needs. Cellular mitochondrial health is maintained by expansing of the mitochondrial pool though mitochondrial biogenesis, by preserving the natural mitochondrial dynamic process, via fusion and fission, and by ensuring the removal of damaged mitochondria through mitophagy. During aging, mitophagy levels decline and negatively impact skeletal muscle performance. Nutritional and pharmacological approaches have been proposed to manage the decline in muscle function due to impaired mitochondria bioenergetics. The natural postbiotic Urolithin A has been shown to promote mitophagy, mitochondrial function and improved muscle function across species in different experimental models and across multiple clinical studies. In this review, we explore the biology of Urolithin A and the clinical evidence of its impact on promoting healthy skeletal muscles during age-associated muscle decline.