Redox Regulation of Satellite Cells and Skeletal Muscle Healing

NCT ID: NCT03711838

Last Updated: 2024-11-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-22
• Study Completion Date: 2022-08-01

Brief Summary

Skeletal muscle stem cells (Satellite cells) are indispensable for muscle growth and remodeling following myofibril damage. Skeletal muscle trauma is present in numerous catabolic conditions, characterized by elevated proteolysis and muscle wasting such as, cancer cachexia and muscular dystrophy, which result in physical capacity impairment and a deteriorated quality of life. Recent studies performed in animals and cell cultures indicate that the increased levels of inflammation and oxidative stress and the reduction of antioxidant defense may blunt the satellite cells response and myogenic programming during muscle healing. However, evidence regarding the effects of redox status on satellite cells and muscle myogenic potential in humans is lacking. Exercise-induced muscle damage bears striking similarities with the aforementioned conditions, which makes it a valuable tool to investigate the redox-dependent regulation of satellite cells during muscle healing. Thus, the objectives of the present study are to examine the effects of redox status perturbation (via N-acetylcysteine administration) on intracellular pathways responsible for satellite cells responses at rest and following aseptic muscle trauma induced by damaging exercise.

Detailed Description

A total number of 40-60 young males aged 18-30 will be initially enrolled in the study. Then, participants will be allocated to either a 1) Low glutathione (GSH-low) or a 2) High glutathione (GSH-high) group based on the basal glutathione levels of their vastus lateralis muscle. In a double-blind, crossover, repeated measures design, participants will consume either Placebo (PLA) or N-acetylcysteine (NAC) before (7-day loading phase), on exercise day and for 8 consecutive days following a single bout of intense exercise (300 eccentric contractions at 30 deg/sec in an isokinetic dynamometer). In both conditions, blood samples and muscle biopsies will be collected at baseline, before the exercise protocol and at 2- and 8-days post-exercise. Muscle performance and soreness will also be assessed at the same time points. Before each trial, participants' dietary intake will be analyzed via diet recalls. Physical activity will be analyzed only at baseline via accelerometry. A 4-week washout period will be implemented between trials. Blood samples will be analyzed for inflammation and oxidative stress markers. Muscle samples will be analyzed for satellite cell responses and myogenic potential, protein levels of intracellular signaling proteins, muscle thiols and antioxidant enzyme activity.

Conditions

Satellite Cells; Redox Status; Exercise-induced Muscle Trauma; Aseptic Inflammation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

N-Acetylcysteine

N-Acetylcysteine supplementation: Orally, 40 mg/kg per day in 3 doses (250 ml each) for 7 consecutive days and immediately post-exercise. The remaining 8 days, 40mg/kg per day in 3 doses (250 ml each).

Group Type: EXPERIMENTAL

N-Acetylcysteine

Intervention Type: DIETARY_SUPPLEMENT

N-Acetylcysteine in a powder form diluted in a 250 ml drink containing 248 ml water and 2 ml of natural, non-caloric, flavoring-sweetener containing sucralose.

Placebo

Placebo administration: Orally 750 ml per day in 3 doses (250 ml each) for 7 consecutive days and immediately post-exercise. The remaining 8 days, 750 ml per day in 3 doses (250 ml each).

Group Type: ACTIVE_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

Placebo consisted of 248 ml water and 2 ml of natural, non-caloric, flavoring-sweetener containing sucralose.

Interventions

N-Acetylcysteine

N-Acetylcysteine in a powder form diluted in a 250 ml drink containing 248 ml water and 2 ml of natural, non-caloric, flavoring-sweetener containing sucralose.

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Placebo consisted of 248 ml water and 2 ml of natural, non-caloric, flavoring-sweetener containing sucralose.

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

1. No recent history of musculoskeletal injury

2. Non-smokers.

3. Abstain from any vigorous physical activity during the study

4. Abstain from consumption of caffeine, alcohol, performance-enhancing or antioxidant supplements, NSAIDs and medications before (at least 6 months) and during the study.

Exclusion Criteria

1. A known NAC intolerance or allergy

2. A recent febrile illness

3. A recent history of muscle lesion and/or lower limb trauma

4. Presence of metabolic diseases

5. Use of anti-inflammatory medication.

6. Use of medication interacting with muscle metabolism.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Thessaly

OTHER

Sponsor Role: lead

Responsible Party

Ioannis G. Fatouros

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Konstantinos Papanikolaou, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Thessaly, School of Physical Education & Sport Science

Locations

Laboratory of Exercise Biochemistry, Exercise Physiology,and Sports Nutrition, School of Physical Education and Sport Science, University of Thessaly

Trikala, Thessaly, Greece

Countries

Greece

References

Papanikolaou K, Jamurtas AZ, Poulios A, Tsimeas P, Draganidis D, Margaritelis NV, Baloyiannis I, Papadopoulos C, Sovatzidis A, Deli CK, Rosvoglou A, Georgakouli K, Tzatzakis T, Nikolaidis MG, Fatouros IG. Skeletal muscle and erythrocyte redox status is associated with dietary cysteine intake and physical fitness in healthy young physically active men. Eur J Nutr. 2023 Jun;62(4):1767-1782. doi: 10.1007/s00394-023-03102-2. Epub 2023 Feb 24.

Reference Type: DERIVED

PMID: 36828945 (View on PubMed)

Papanikolaou K, Draganidis D, Chatzinikolaou A, Laschou VC, Georgakouli K, Tsimeas P, Batrakoulis A, Deli CK, Jamurtas AZ, Fatouros IG. The redox-dependent regulation of satellite cells following aseptic muscle trauma (SpEED): study protocol for a randomized controlled trial. Trials. 2019 Jul 31;20(1):469. doi: 10.1186/s13063-019-3557-3.

Reference Type: DERIVED

PMID: 31366396 (View on PubMed)

Other Identifiers

Satellite Cells - UTH

Identifier Type: -

Identifier Source: org_study_id