Clinical trial NCT03711838: Redox Regulation of Satellite Cells and Skeletal Muscle Healing
Official title: The Effect of Redox Potential on the Regulation of Satellite Cells and Skeletal Muscle Healing Following Exercise-Induced Muscle Damage
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Satellite Cells
Redox Status
Exercise-induced Muscle Trauma
Aseptic Inflammation
Keywords: Pax7
MyoD
Antioxidants
Myogenic potential
Skeletal muscle healing
Lead sponsor: University of Thessaly
Sponsor class: OTHER
First posted: 2018-10-19
Enrollment: 45
Sex: MALE
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: Change in muscle satellite cells number (i.e. Pax7+ cells) and activation status (i.e. Pax7+/MyoD+ cells)
timeFrame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
measure: Change in muscle myogenic mRNA expression
timeFrame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
measure: Change in muscle inflammatory state
timeFrame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
measure: Change in intracellular antioxidant enzymes in muscle
timeFrame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
measure: Change in muscle thiol content
timeFrame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
measure: Change in intracellular signaling proteins in muscle
timeFrame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
measure: Change in skeletal muscle damage levels
timeFrame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Secondary outcomes:
measure: Resting metabolic rate (RMR)
timeFrame: At baseline
measure: Body composition
timeFrame: At baseline
measure: Maximal oxygen consumption (VO2max)
timeFrame: At baseline
measure: Isokinetic strength
timeFrame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
measure: Change in delayed onset of muscle soreness (DOMS)
timeFrame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
measure: Physical activity
timeFrame: At baseline.
measure: Dietary intake
timeFrame: At baseline.
measure: Interleukin-1β (IL-1β) in blood
timeFrame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
measure: Interleukin-6 (IL-6) in blood
timeFrame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
measure: Interleukin-8 (IL-8) in blood
timeFrame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
measure: Interleukin-10 (IL-10) in blood
timeFrame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
measure: Cortisol in blood
timeFrame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
measure: Protein carbonyls (PC)
timeFrame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
measure: Malondialdehyde (MDA)
timeFrame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
measure: Total antioxidant capacity (TAC)
timeFrame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
measure: Catalase
timeFrame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
measure: Creatine Kinase (CK)
timeFrame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
measure: White blood cell count in blood
timeFrame: At baseline, before the exercise protocol and at days 2 and 8 following exercise.
Other outcomes:
Locations:
city: Trikala
country: Greece
facility: Laboratory of Exercise Biochemistry, Exercise Physiology,and Sports Nutrition, School of Physical Education and Sport Science, University of Thessaly
state: Thessaly
Study officials:
affiliation: University of Thessaly, School of Physical Education & Sport Science
name: Konstantinos Papanikolaou, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.