Oral Supplementation for COPD

Overseen By Bryan Ross, MD, FRCPC, MSc (Epi, Physiol)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Must not be taking: Oral corticosteroids, Anticoagulants

Disqualifiers: Severe cardiac disease, Neurological conditions, Orthopedic conditions, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

10 Participants Needed

Trial Summary

What is the purpose of this trial?

Chronic obstructive pulmonary disease (COPD) is a very common and chronic lung condition and is a leading cause of morbidity and death. These patients have persistent breathlessness and exercise intolerance, affecting their ability to carry out routine daily tasks. Standard COPD treatments include medicines/puffers as well as participation in a Pulmonary Rehabilitation (PR) program. PR programs are delivered by a diverse team of healthcare experts in exercise and nutrition. It is possible that an emerging nutritional oral supplement could target the muscular dysfunction seen in patients with COPD in part by promoting better working mitochondria, the energy 'engine' of muscle. A series of recently published studies in sedentary adults and in older adults have demonstrated the safety, tolerability, and potential clinical effectiveness of this supplement. In this regard, the investigators plan to lead a large randomized controlled trial (RCT) to test whether oral supplementation in patients with COPD who are also participating in a standard PR program will improve overall exercise performance. The investigators will also test muscle strength, cognition, body composition, and other clinically important outcomes such as quality of life. Lastly, the investigators will use muscle tissue from a subgroup of volunteers to investigate the effect on muscle/mitochondrial structure/function. The focus is actually the critical 'first step' before the larger RCT: a pilot and feasibility study on a smaller number of participants with COPD, as an important proof-of-concept that the larger study can, and should, be conducted.

Will I have to stop taking my current medications?

The trial does not specify that you need to stop taking your current medications, but you must avoid certain supplements and foods like Coenzyme Q10, resveratrol, L-carnitine, pomegranate juice, walnuts, pecans, strawberries, raspberries, and blackberries starting 7 days before and during the trial.

What data supports the effectiveness of the treatment Urolithin A for COPD?

Research shows that Urolithin A can improve cellular health by enhancing mitochondrial function and reducing inflammation, which may be beneficial for conditions like COPD. It has also been shown to improve muscle health in elderly individuals, suggesting potential benefits for respiratory muscles in COPD patients. ^{1 2 3 4 5}

Is Urolithin A safe for human consumption?

Urolithin A, a compound found in foods like pomegranates and nuts, has been studied for safety in animals and showed no harmful effects at high doses. It is not genotoxic (does not damage genetic information) and did not cause any toxic effects in animal studies, suggesting it is generally safe for consumption. ^{1 2 5 6 7}

How is the drug Urolithin A different from other COPD treatments?

Urolithin A is unique for COPD as it is an oral supplement, unlike the common inhaled bronchodilators used in COPD treatment. It may offer a novel approach by potentially targeting cellular health and energy production, which is different from the typical focus on opening airways. ^{8 9 10 11 12}

Eligibility Criteria

This trial is for individuals with Chronic Obstructive Pulmonary Disease (COPD) who are already participating in a Pulmonary Rehabilitation program. The study aims to see if adding a nutritional supplement can improve muscle function and overall health.

Inclusion Criteria

I am over 40 and have a history of smoking at least 10 pack-years.

My lung function is reduced, fitting into moderate to very severe COPD categories.

I have received at least 2 doses of a COVID-19 vaccine.

Exclusion Criteria

Inability to provide consent due to language or cognitive barrier

I had a COPD flare-up in the last 4 weeks.

Previous PR participation in the last 12 months, or in a study involving an exercise program in the last 6 months

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Urolithin A supplementation or placebo during an 8-week Pulmonary Rehabilitation program

8 weeks

Weekly visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Urolithin A

Trial Overview The trial is testing the effects of Urolithin A, an oral supplement thought to enhance muscle energy production, against a placebo. It's part of a pilot study to determine if larger trials should be conducted on its benefits alongside standard COPD treatments.

Participant Groups

Group I: Intervention (Urolithin A: Mitopure) Group Active Control 1 Intervention

Participants will participate in a standard PR program and will receive the oral supplement.

Group II: Placebo Group Placebo Group 1 Intervention

Participants will participate in a standard PR program and will receive placebo.

Urolithin A is already approved in United States, European Union for the following indications:

Approved in United States as Urolithin A for:

• Generally Recognized as Safe (GRAS) for dietary supplement use

Approved in European Union as Urolithin A for:

• No specific therapeutic indications approved; available as a dietary supplement

Who Is Running the Clinical Trial?

McGill University Health Centre/Research Institute of the McGill University Health Centre

Lead Sponsor

Trials

476

Recruited

170,000+

Amazentis SA

Industry Sponsor

Trials

21

Recruited

1,400+

Findings from Research

Urolithin A (UA), derived from gut bacteria processing ellagitannins found in foods like pomegranate and berries, has been shown to enhance cellular health by promoting mitophagy and improving mitochondrial function while reducing inflammation.

Recent clinical trials indicate that UA supplementation can provide benefits for muscle health in elderly individuals, suggesting its potential as a nutritional intervention to combat aging and age-related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of the Natural Compound Urolithin A on Health, Disease, and Aging. D'Amico, D., Andreux, PA., Valdés, P., et al.[2021]

Urolithin A (UroA) effectively inhibits the growth of both androgen receptor-positive (AR+) and androgen receptor-negative (AR-) prostate cancer cells, with AR+ cells being more sensitive to its effects, indicating its potential as a targeted therapy for castration-resistant prostate cancer (CRPC).

Oral administration of UroA significantly reduced the growth of AR+ C4-2B xenografts in animal models without causing toxicity, and it works by downregulating androgen receptor signaling, suggesting its promise as a safe and effective treatment option for CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A natural molecule, urolithin A, downregulates androgen receptor activation and suppresses growth of prostate cancer. Dahiya, NR., Chandrasekaran, B., Kolluru, V., et al.[2020]

Urolithin A (UroA), derived from foods like pomegranates and walnuts, shows promise as a therapeutic agent due to its ability to reduce inflammation in various tissues, which may help prevent diseases like Alzheimer's and type 2 diabetes.

Research indicates that UroA's anti-inflammatory effects could be harnessed through dietary sources or as a pharmaceutical treatment, highlighting its potential role in managing immunometabolic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulatory Role of Urolithin A on Metabolic Diseases. Toney, AM., Fox, D., Chaidez, V., et al.[2021]

Urolithin A (UA) was found to be safe for consumption in a first-in-human clinical trial involving healthy, sedentary elderly individuals, with a favorable safety profile observed during the study.

After 4 weeks of treatment with UA at doses of 500 mg and 1,000 mg, participants showed changes in plasma acylcarnitines and improved skeletal muscle mitochondrial gene expression, indicating potential benefits for mitochondrial and cellular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Andreux, PA., Blanco-Bose, W., Ryu, D., et al.[2021]

Urolithin A (URA) demonstrated a significant therapeutic effect in an experimental autoimmune encephalomyelitis (EAE) model, effectively suppressing disease progression at various stages when administered orally at a dose of 25 mg/kg/day.

URA works by inhibiting the activation of dendritic cells and Th17 cell differentiation, targeting the Aryl Hydrocarbon Receptor (AhR) to modulate immune signaling pathways, suggesting its potential as a treatment for autoimmune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urolithin A ameliorates experimental autoimmune encephalomyelitis by targeting aryl hydrocarbon receptor. Shen, PX., Li, X., Deng, SY., et al.[2021]

Urolithin A (UA), a metabolite from foods like pomegranates, was found to be non-genotoxic in a series of tests, indicating it does not damage genetic material.

In a 90-day study with rats, UA showed no adverse effects on health at doses up to 5% of their diet, suggesting it is safe for consumption at high levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety assessment of Urolithin A, a metabolite produced by the human gut microbiota upon dietary intake of plant derived ellagitannins and ellagic acid. Heilman, J., Andreux, P., Tran, N., et al.[2018]

Urolithin A (UA), a compound produced by gut bacteria from dietary ellagitannins, has shown potential in providing gastrointestinal protection, particularly through its anticancer and anti-inflammatory effects.

Research indicates that UA can regulate various tumor and inflammatory signaling pathways and enhance enzyme activity related to cancer defense, suggesting its usefulness in treating gastrointestinal diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential of the ellagic acid-derived gut microbiota metabolite - Urolithin A in gastrointestinal protection. Kujawska, M., Jodynis-Liebert, J.[2021]

In a 24-week study involving 1532 patients with COPD, the combination treatment of umeclidinium/vilanterol (UMEC/VI) significantly improved lung function (measured by FEV1) compared to both placebo and the individual components (UMEC and VI) alone.

UMEC/VI was well tolerated, showing no significant adverse effects, and led to meaningful improvements in symptoms and quality of life, including reduced need for rescue medication and better scores on health-related questionnaires.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of once-daily umeclidinium/vilanterol 62.5/25 mcg in COPD. Donohue, JF., Maleki-Yazdi, MR., Kilbride, S., et al.[2022]

The dual bronchodilator umeclidinium/vilanterol (UMEC/VI) is more cost-effective for treating moderate to very severe COPD than tiotropium (TIO) and open dual LAMA + LABA treatments, with lower lifetime medical costs and fewer predicted exacerbations.

Patients treated with UMEC/VI experienced an increase in quality-adjusted life-years (QALYs) compared to those on TIO and no long-acting bronchodilator, indicating not only cost savings but also improved health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of umeclidinium/vilanterol for the management of patients with moderate to very severe COPD using an economic model. Wilson, MR., Patel, JG., Coleman, A., et al.[2022]

The fixed-dose combination (FDC) of aclidinium and formoterol significantly improved symptoms and lung function in patients with stable COPD compared to aclidinium, formoterol, or placebo, with a notable increase in quality of life and dyspnoea relief.

While the FDC did not show a significant difference in exacerbations or serious adverse events compared to monotherapy or placebo, it demonstrated a lower risk of moderate exacerbations and adverse events compared to formoterol, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined aclidinium bromide and long-acting beta2-agonist for chronic obstructive pulmonary disease (COPD). Ni, H., Moe, S., Soe, Z., et al.[2022]

The fixed-dose combination of glycopyrrolate and formoterol (GFF MDI) significantly improved lung function in patients with moderate-to-very severe COPD after 7 days of treatment, outperforming monocomponent inhalers and placebo.

Both doses of GFF MDI (72/9.6 μg and 36/9.6 μg) were well tolerated, indicating a favorable safety profile for this combination therapy in managing COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, seven-day study to assess the efficacy and safety of a glycopyrrolate/formoterol fumarate fixed-dose combination metered dose inhaler using novel Co-Suspension™ Delivery Technology in patients with moderate-to-very severe chronic obstructive pulmonary disease. Reisner, C., Fabbri, LM., Kerwin, EM., et al.[2022]

The combination bronchodilator UMEC/VI (umeclidinium/vilanterol) has been shown to be an effective once-daily treatment for COPD, improving pulmonary function in over 4,500 patients studied in large clinical trials.

New bronchodilator combinations, like UMEC/VI, aim to enhance treatment compliance by allowing for once-daily dosing, which could lead to better management of COPD symptoms and potentially reduce exacerbations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential pharmacology and clinical utility of emerging combination treatments in the management of COPD--role of umeclidinium/vilanterol. Malerba, M., Morjaria, JB., Radaeli, A.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Impact of the Natural Compound Urolithin A on Health, Disease, and Aging. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

A natural molecule, urolithin A, downregulates androgen receptor activation and suppresses growth of prostate cancer. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Immunomodulatory Role of Urolithin A on Metabolic Diseases. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Urolithin A ameliorates experimental autoimmune encephalomyelitis by targeting aryl hydrocarbon receptor. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Safety assessment of Urolithin A, a metabolite produced by the human gut microbiota upon dietary intake of plant derived ellagitannins and ellagic acid. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Potential of the ellagic acid-derived gut microbiota metabolite - Urolithin A in gastrointestinal protection. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of once-daily umeclidinium/vilanterol 62.5/25 mcg in COPD. [2022]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of umeclidinium/vilanterol for the management of patients with moderate to very severe COPD using an economic model. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Combined aclidinium bromide and long-acting beta2-agonist for chronic obstructive pulmonary disease (COPD). [2022]

11. England pubmed.ncbi.nlm.nih.gov

A randomized, seven-day study to assess the efficacy and safety of a glycopyrrolate/formoterol fumarate fixed-dose combination metered dose inhaler using novel Co-Suspension™ Delivery Technology in patients with moderate-to-very severe chronic obstructive pulmonary disease. [2022]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Differential pharmacology and clinical utility of emerging combination treatments in the management of COPD--role of umeclidinium/vilanterol. [2021]