Oral Supplementation During PR Participation in COPD

Copd Clinical Trial

Official title:

Urolithin A Supplementation During Pulmonary Rehabilitation Participation in Patients With Chronic Obstructive Pulmonary Disease: a Randomized Pilot and Feasibility Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06324214
• Other study ID #: 2023-9352
• Status: Recruiting
• Phase: Phase 2
• Start date: March 11, 2024
• Est. completion date: May 31, 2025

Study information

• Verified date: March 2024
• Source: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Contact: Bryan Ross, MD, FRCPC, MSc (Epi, Physiol)
• Phone: (514) 843-1465
• Email: bryan.ross[@]mcgill.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The main objectives for this pilot feasibility study are to document recruitment rates, collect information on participant acceptability of tests, establish the capacity to run the RCT at our site, to demonstrate successful molecular testing of specimens, and to generate pilot data for the outcomes being tested in the larger subsequent RCT. The overarching goal for the 'larger', future project will be to determine the effect of the oral supplement on exercise capacity, muscle strength, mitochondrial function, health-related quality of life, cognition, symptom burden, and safety/adherence in patients with COPD who are participating in a Pulmonary Rehabilitation program. The goal of the present research project is to complete a pilot and feasibility study testing the same clinical outcomes on a smaller sample of eligible study participants during which participants receive the intervention for 8 weeks. The primary objective is to determine whether administration of the oral supplement during participation in a standard multi-week in-person Pulmonary Rehabilitation (PR) program is associated with an improvement in exercise endurance capacity in patients with COPD, compared with PR participation and placebo supplementation. The secondary objectives are to determine the effect of the oral supplement on i) global conditioning and exercise capacity; ii) muscle strength; iii) mitochondrial function; iv) body composition; v) quality of life and burden of disease; vi) cognition; vii) adverse events/complications and adherence, and viii) blood levels of Urolithin A. We hypothesize that patients with COPD receiving oral supplementation during PR participation will demonstrate an improvement in Constant Work Rate Exercise Test (CRWET) time after 8 weeks when compared to patients with COPD who receive placebo and PR participation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: May 31, 2025
• Est. primary completion date: March 4, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

1. Males and females, aged >40, former smokers with =10 pack-year smoking history

2. 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

3. Baseline 6MWD of =50m

4. Prior receipt of at least 2 doses of the Coronavirus Disease of 2019 (COVID-19) vaccine

Exclusion Criteria:

1. Inability to participate in a standard PR program

2. Severe/unstable cardiac disease, neurological or orthopedic conditions which could hinder exercise performance

3. Inability to provide consent due to language or cognitive barrier

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

5. Experienced an exacerbation of COPD (ECOPD) within the prior 4 weeks

6. Long-term oxygen therapy use, or maintenance oral corticosteroid use

7. Presence of pacemaker or implantable cardioverter defibrillator (ICD) (unless participant opts out of bioelectrical impedance assay)

8. 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

9. 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

10. Allergy to lecithin, to soy or to sunflower

11. Pregnant, breastfeeding or planning to become pregnant

12. Use of anticoagulant or presence of a clotting disorder (if participating in muscle biopsy subgroup)

13. Allergy to anesthetics such as xylocaine and lidocaine (if participating in muscle biopsy subgroup)

14. Chronic myalgia, fibromyalgia or conditions characterized by regular muscle pain (if participating in muscle biopsy subgroup)

15. Metal fixation plates or screws in the legs from a previous surgery (if participating in muscle biopsy subgroup)

Related Conditions & MeSH terms

• Copd

Intervention

Dietary Supplement:
• Urolithin A (Mitopure)
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.

Other:
• Placebo
Placebo.

Locations

Country	Name	City	State
Canada	McGill University Health Centre	Montréal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
McGill University Health Centre/Research Institute of the McGill University Health Centre	Amazentis SA

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	6-Minute Walk Test (6MWT)	6-Minute Walk Distance (6MWD) obtained on a standard 6MWT	Pre-intervention (baseline) and Post-intervention (after 8 weeks)
Secondary	Quadriceps strength	4-second maximum quadriceps strength test	Pre-intervention (baseline) and Post-intervention (after 8 weeks)
Secondary	Mitochondrial function	Fresh samples	Pre-intervention (baseline) and Post-intervention (after 8 weeks)
Secondary	Muscle histology	Stains for mitochondrial markers (including succinate dehydrogenase (SDH)): post-intervention in comparison to pre-intervention.	Pre-intervention (baseline) and Post-intervention (after 8 weeks)
Secondary	Tissue microscopy	Transmission electron microscopy for assessment of number of mitochondria: post-intervention in comparison to pre-intervention.	Pre-intervention (baseline) and Post-intervention (after 8 weeks)
Secondary	Tissue microscopy	Transmission electron microscopy for assessment of morphology of mitochondria: post-intervention in comparison to pre-intervention.	Pre-intervention (baseline) and Post-intervention (after 8 weeks)
Secondary	Specific protein detection	Targeted Western blot analysis for proteins related to mitochondrial function: post-intervention in comparison to pre-intervention.	Pre-intervention (baseline) and Post-intervention (after 8 weeks)
Secondary	RNA analyses	Specific mRNA transcript changes related to mitochondrial function and whole transcriptome changes: post-intervention in comparison to pre-intervention.	Pre-intervention (baseline) and Post-intervention (after 8 weeks)
Secondary	Body composition	Dual X-ray absorptiometry (DXA) scan	Pre-intervention (baseline) and Post-intervention (after 8 weeks)
Secondary	Body impedance	Bioelectrical impedance assay (BIA)	Pre-intervention (baseline) and Post-intervention (after 8 weeks)
Secondary	Disease-specific impact on quality of life	St. George's respiratory questionnaire (SGRQ)	Pre-intervention (baseline) and Post-intervention (after 8 weeks)
Secondary	Burden of disease	COPD assessment test (CAT)	Pre-intervention (baseline) and Post-intervention (after 8 weeks)
Secondary	Cognition	Stroop test	Pre-intervention (baseline) and Post-intervention (after 8 weeks)
Secondary	Adverse events	Adverse events (AEs) will be monitored from the signing of the Informed Consent Form (ICF) through completion of study participation. If any AEs do occur, study participants will be followed until symptoms have resolved or have returned to baseline levels. All outstanding AEs will be followed until resolution or until the participant's last study visit.	12 weeks
Secondary	Differences in dosed missed	The total number of doses missed will be recorded and reported.	8 weeks
Secondary	Blood levels of the intervention	Blood levels of Urolithin A will be collected at the mid-point of the study.	Day 28