Oral Supplementation During PR Participation in COPD

NCT06324214 | Recruiting Phase 2

• 1 other identifier: 2023-9352
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Copd

Outcome Measures

Primary Outcomes (1)

• Constant Work Rate Exercise Test (CRWET)

  Exercise test whereby the workload is constant and is calculated as a percentage of the peak power output observed in the incremental test.

  Pre-intervention (baseline) and Post-intervention (after 8 weeks)

Secondary Outcomes (16)

• 6-Minute Walk Test (6MWT)

  Pre-intervention (baseline) and Post-intervention (after 8 weeks)

• Quadriceps strength

  Pre-intervention (baseline) and Post-intervention (after 8 weeks)

• Mitochondrial function

  Pre-intervention (baseline) and Post-intervention (after 8 weeks)

• Muscle histology

  Pre-intervention (baseline) and Post-intervention (after 8 weeks)

• Tissue microscopy

  Pre-intervention (baseline) and Post-intervention (after 8 weeks)

Study Arms (2)

Placebo Group

PLACEBO COMPARATOR

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

Other: Placebo

Intervention (Urolithin A: Mitopure) Group

ACTIVE COMPARATOR

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

Dietary Supplement: Urolithin A (Mitopure)

Interventions

Urolithin A (Mitopure) DIETARY_SUPPLEMENT

Compound belonging to the 'urolithin' class. First discovered over 40 years ago as a gut-derived metabolite in rats and subsequently in humans. A food and dietary ingredient, and more specifically, a post-biotic compound. Derived from ellagitannins, which are present in foods such as pomegranate, berries, and walnuts. An 'inducer' of mitophagy.

Intervention (Urolithin A: Mitopure) Group

Placebo OTHER

Placebo.

Placebo Group

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females, aged \>40, former smokers with ≥10 pack-year smoking history
• Post-bronchodilator forced expiratory volume at one second (FEV1) / forced vital capacity (FVC) ratio \< 0.7, with FEV1 \< 80% (moderate, Global Initiative for Chronic Obstructive Lung Disease '(GOLD) 2') FEV1 \< 50% (severe, 'GOLD 3') or FEV1 \< 30% (very severe, 'GOLD 4') COPD
• Baseline 6MWD of ≥50m
• Prior receipt of at least 2 doses of the Coronavirus Disease of 2019 (COVID-19) vaccine

You may not qualify if:

• Inability to participate in a standard PR program
• Severe/unstable cardiac disease, neurological or orthopedic conditions which could hinder exercise performance
• Inability to provide consent due to language or cognitive barrier
• Previous PR participation in the last 12 months, or in a study involving an exercise program in the last 6 months
• Experienced an exacerbation of COPD (ECOPD) within the prior 4 weeks
• Long-term oxygen therapy use, or maintenance oral corticosteroid use
• Presence of pacemaker or implantable cardioverter defibrillator (ICD) (unless participant opts out of bioelectrical impedance assay)
• Unwilling to agree to refrain from using, or are found to be using, the following supplementary antioxidant vitamins from 7 days prior to dosing and throughout the treatment period: Coenzyme Q10, resveratrol, and L-carnitine
• Unwilling to agree to refrain from using, or are found to be using, the following dietary restrictions from 7 days prior to dosing and throughout the treatment period: pomegranate juice, walnuts, pecans, strawberries, raspberries, and blackberries
• Allergy to lecithin, to soy or to sunflower
• Pregnant, breastfeeding or planning to become pregnant
• Use of anticoagulant or presence of a clotting disorder (if participating in muscle biopsy subgroup)
• Allergy to anesthetics such as xylocaine and lidocaine (if participating in muscle biopsy subgroup)
• Chronic myalgia, fibromyalgia or conditions characterized by regular muscle pain (if participating in muscle biopsy subgroup)
• Metal fixation plates or screws in the legs from a previous surgery (if participating in muscle biopsy subgroup)

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead
• Amazentis SA: collaborator

Study Sites (1)

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

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

CONTACT

(514) 843-1465; bryan.ross@mcgill.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 4, 2024
• First Posted: March 21, 2024
• Study Start: March 11, 2024
• Primary Completion: March 4, 2025
• Study Completion: May 31, 2025
• Last Updated: April 2, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)