The Effects of Protein Supplementation With or Without Urolithin A During Single-leg Immobilization

Comparison of High-protein Formulation With/Without Urolithin a During a Unilateral Knee Immobilization: a Pilot Proof-of-concept Trial

There are times in life when people cannot use their muscles, such as during illness or injury. Muscle and mitochondria (the 'energy factory' in cells) health decline very quickly when people cannot use their muscles, but certain foods can help reduce these declines. Recent research suggests that Urolithin A, which is a natural compound that can be produced after eating pomegranates, nuts, and berries, improves muscle health. In this study, the investigators aim to investigate if a protein beverage (standard care during disuse) with or without Urolithin A can reduce or prevent the loss of muscle health while wearing a knee brace (muscle disuse).

Study Overview

• Status: Recruiting
• Conditions: Healthy; Muscle Disuse Atrophy
• Intervention / Treatment: Dietary supplement: Protein supplement; Dietary supplement: Protein supplement with Urolithin A

Detailed Description

After participants provide informed consent to participate and are deemed eligible for the study (Day 0), participants will sequentially complete the three phases of this study:

1. RUN-IN phase: participants continue habitual lifestyle (Day 7-Day 14 [1 week])
2. IMMOBILIZATION phase: participants undergo 2 weeks of unilateral knee immobilization (Day 14-Day 28 [2 weeks])
3. RECOVERY phase: participants return to habitual lifestyle (Day 28-Day 35 [1 week])

Participants will consume their randomly assigned supplement daily during all three phases.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Brad Currier; Phone Number: 9055259140; Email: currierb@mcmaster.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada
      • Recruiting
      • McMaster University
      • Contact: Brad Currier; Phone Number: 9055259140; Email: currierb@mcmaster.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Men aged 18-30 years
2. Healthy, non-smoking
3. BMI between 20 and 30 kg/m^2
4. No orthopedic issues that would preclude participation in the knee bracing protocol
5. Not taking any medication or with any medical condition that, in the opinion of the investigators, would compromise the study outcome or the safety of the research participant
6. Provide informed consent
7. Understand COVID-19 risks and procedures for in person research and sign Information Letter: COVID-19 Risks and Procedures for In-Person Research at McMaster University

Exclusion Criteria:

1. Subject has any concurrent medical, orthopedic, or psychiatric requirements that, in the opinion of the investigators, would compromise their ability to comply with the study requirements
2. Clinically significant abnormal laboratory results at screening
3. Participation in a clinical research trial within 30 days before randomization
4. Allergy or sensitivity to study ingredients
5. Individuals who are cognitively impaired and/or who are unable to give informed consent
6. Any other condition that, in the opinion of the investigators, may adversely affect the subject's ability to complete the study or its measures or may pose a significant risk to the subject
7. Any cachexia-related condition or any genetic muscle diseases or disorders
8. Current gastrointestinal condition that could interfere with the study (e.g., IBS/IBD [irritable bowel syndrome/inflammatory bowel disease], diarrhea, acid reflux disease, dysphagia, etc.)
9. Excessive alcohol consumption (>21 units/week) and/or a smoker (cigarettes or vaping)
10. Concomitant use of corticosteroids, antibiotics, any anabolic steroid, creatine, whey protein supplements, casein, branched-chain amino acids (BCAAs) or any other NHP [Natural Health Product], medication or supplement used for muscle strengthening/building within 45 days prior to screening
11. Contraindications to an MRI scan (metal implants, metal-based ink tattoo)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Protein supplement	Dietary supplement: Protein supplement; Ready-to-drink protein beverage consumed once daily for 28 days
Experimental: Protein supplement with Urolithin A	Dietary supplement: Protein supplement with Urolithin A; Ready-to-drink protein beverage with 1000 mg of Urolithin A consumed once daily for 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in maximal mitochondrial respiration (rate of oxygen flux) and mitochondrial ADP [adenosine diphosphate] sensitivity (Oroboros O2k)	Oxygen flux in muscle measured using Oroboros	Outcome measured and reported for: Day 7, Day 14, Day 28, Day 35

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle strength (Biodex)	Isometric leg extension strength	Day 7, Day 14, Day 28, Day 35
Quadriceps muscle size	Muscle size measured using MRI	Outcome measured and reported for: Day 14, Day 28, Day 35
Muscle protein fractional synthetic rate	Protein synthetic rate using labelled alanine incorporation	Day 7, Day 14, Day 28, Day 35; integrated synthesis rates reported for Day 7-14, Day 14-28; Day 28-35

Collaborators and Investigators

• Sponsor: McMaster University
• Investigators: Principal Investigator: Stuart Phillips, McMaster University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2023
• Primary Completion (Estimated): May 31, 2024
• Study Completion (Estimated): September 30, 2024

Study Registration Dates

• First Submitted: March 10, 2023
• First Submitted That Met QC Criteria: April 3, 2023
• First Posted (Actual): April 18, 2023

Study Record Updates

• Last Update Posted (Actual): October 19, 2023
• Last Update Submitted That Met QC Criteria: October 18, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic
• Other Study ID Numbers: 13783; ISRCTN20052152 (Registry Identifier: International Standard Randomised Controlled Trial Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No