Redox Regulation of Satellite Cells and Skeletal Muscle Healing

November 16, 2024 updated by: Ioannis G. Fatouros, University of Thessaly

The Effect of Redox Potential on the Regulation of Satellite Cells and Skeletal Muscle Healing Following Exercise-Induced Muscle Damage

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and 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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
45

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Greece
    • Thessaly
      • Trikala, Thessaly, Greece, 42100
        • Laboratory of Exercise Biochemistry, Exercise Physiology,and Sports Nutrition, School of Physical Education and Sport Science, University of Thessaly

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 26 years (Adult)

Accepts Healthy Volunteers

Yes

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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).
Dietary supplement: 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.
Active Comparator: 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).
Dietary supplement: Placebo
Placebo consisted of 248 ml water and 2 ml of natural, non-caloric, flavoring-sweetener containing sucralose.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in muscle satellite cells number (i.e. Pax7+ cells) and activation status (i.e. Pax7+/MyoD+ cells)
Time Frame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Satellite cells number and activation status, will be assessed in muscle via immunohistochemistry.
At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Change in muscle myogenic mRNA expression
Time Frame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
mRNA expression levels of Myogenic factor 5 (Myf5), myogenin and Myogenic factor 6 (Myf6/MRF4) and myostatin will be assessed in muscle using Real-Time Polymerase Chain Reaction (RT-PCR).
At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Change in muscle inflammatory state
Time Frame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Pro-inflammatory (M1+) and anti-inflammatory (M2+) macrophages will be measured in muscle using immunohistochemistry.
At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Change in intracellular antioxidant enzymes in muscle
Time Frame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Protein levels of Glutathione peroxidase 3 (GPx3), Superoxide dismutase 1 (SOD1) and Thioredoxin (Trx1) will be measured using western blotting.
At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Change in muscle thiol content
Time Frame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Concentration levels of reduced glutathione (GSH) and oxidized glutathione (GSSG) will be measured spectophotometrically.
At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Change in intracellular signaling proteins in muscle
Time Frame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Protein levels of IGF-1, Notch1 and Wnt3 will be measured using western blotting.
At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Change in skeletal muscle damage levels
Time Frame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Skeletal muscle damage will be quantified via histochemistry using H&E staining.
At baseline, before the exercise protocol and at days 2 and 8 following exercise.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Resting metabolic rate (RMR)
Time Frame: At baseline
RMR will be assessed after an overnight fast with participants in a supine position following a 15-min stabilization period by taking 30 consecutive 1-min VO2/CO2 measurements using a portable open-circuit indirect calorimeter with a ventilated hood system following a standard calibration protocol.
At baseline
Body composition
Time Frame: At baseline
Body composition will be measured using a dual-energy x-ray absorptiometry scanner (DXA).
At baseline
Maximal oxygen consumption (VO2max)
Time Frame: At baseline
VO2max will be assessed during continuous incremental running to volitional fatigue on a treadmill with a pulmonary gas exchange system (Oxycon Mobile; Sensor-Medics Corporation).
At baseline
Isokinetic strength
Time Frame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Maximal knee extensor eccentric peak torque at 60 degrees will be assessed on an isokinetic dynamometer.
At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Change in delayed onset of muscle soreness (DOMS)
Time Frame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Muscle soreness will assessed during palpation of the muscle belly and the distal region of relaxed vastus medialis, vastus lateralis and rectus femoris following three repetitions of of a full squat. Subjects will rate their DOMS on a visual analogue scale (0-10).
At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Physical activity
Time Frame: At baseline.
Level of habitual physical activity will be assessed using accelerometry (ActiGraph GT3X-BT accelerometer).
At baseline.
Dietary intake
Time Frame: At baseline.
Daily dietary intake will be assessed using 7-day diet recalls.
At baseline.
Interleukin-1β (IL-1β) in blood
Time Frame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Concentration of IL-1β will be measured in plasma.
At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Interleukin-6 (IL-6) in blood
Time Frame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Concentration of IL-6 will be measured in plasma.
At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Interleukin-8 (IL-8) in blood
Time Frame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Concentration of IL-6 will be measured in plasma.
At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Interleukin-10 (IL-10) in blood
Time Frame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Concentration of IL-10 will be measured in plasma.
At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Cortisol in blood
Time Frame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Concentration of cortisol will be measured in serum.
At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Protein carbonyls (PC)
Time Frame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Concentration of protein carbonyls will be measured in muscle.
At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Malondialdehyde (MDA)
Time Frame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Concentration of malondialdehyde will be measured in muscle.
At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Total antioxidant capacity (TAC)
Time Frame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Concentration of TAC will be measured in serum.
At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Catalase
Time Frame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Concentration of catalase will be measured in red blood cell lysate.
At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Creatine Kinase (CK)
Time Frame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Concentration of CK will be measured in serum.
At baseline, before the exercise protocol and at days 2 and 8 following exercise.
White blood cell count in blood
Time Frame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
White blood cell count will be measured in blood. White blood cell count will be measured in blood.
At baseline, before the exercise protocol and at days 2 and 8 following exercise.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Thessaly

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Konstantinos Papanikolaou, PhD, University of Thessaly, School of Physical Education & Sport Science

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 22, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 11, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 16, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 19, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 20, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 16, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Satellite Cells - UTH

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings