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Redox Status and Immune Function

Primary Purpose

Skeletal Muscle Damage, Aseptic Inflammation, Skeletal Muscle Function

Status
Completed
Phase
Not Applicable
Locations
Greece
Study Type
Interventional
Intervention
n-acetylcysteine
Placebo
Sponsored by
National and Kapodistrian University of Athens
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Skeletal Muscle Damage focused on measuring muscle injury, exercise, redox status, immune cells

Eligibility Criteria

18 Years - 30 Years (Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria:

  • Recreationally trained (VO2max > 45 ml/kg/min)
  • Engaged in regular exercise for ≥3 times/week for > 12 months
  • non-smokers
  • Abstain from exercise during the course of the two trials
  • No consumption of performance-enhancing substances, antioxidants, caffeine, alcohol and/or medications during the study.

Exclusion Criteria:

  • NAC intolerance
  • Recent musculoskeletal injuries of the lower limbs
  • Febrile illness
  • History of muscle lesion.

Sites / Locations

  • University of Athens, Medical School, Department of Clinical Therapeutics

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

n-acetylcysteine

Placebo

Arm Description

orally in three daily dosages, at 20 mg/kg/day, daily for eight days after exercise

orally in three daily dosages, content: 500 mL drink that contained water (375 mL), sugar-free cordial (125 ml), and 2 g of low-calorie glucose/dextrose powder

Outcomes

Primary Outcome Measures

Changes in protein carbonyls in red blood cells
Concentration of protein carbonyls
Changes in thiobarbituric acid reactive substances in red blood cells
Thiobarbituric acid reactive substances concentration in red blood cells
Changes in total antioxidant capacity in serum
Changes in reduced glutathione in blood
Concentration of reduced glutathione in red blood cells
Changes in oxidized glutathione in blood
Concentration of oxidized glutathione in red blood cells
Changes in catalase activity in red blood cells
Changes in creatine kinase activity in serum
Changes in high sensitivity C-reactive protein in serum
Changes in white blood cell count in blood
Changes in adhesion molecule concentration in blood
Measurement of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular cell adhesion molecule-1 (sICAM-1) concentrations in plasma
Changes in cytokine concentration in serum
Measurement of interleukin-1β (IL-1β) and interleukin-6 (IL-6)
Changes in neutrophil count in blood
Cytofluorometric analysis of neutrophil count in blood
Changes in lymphocyte count in blood
Cytofluorometric analysis of lymphocyte count in blood
Changes in monocyte count in blood
Cytofluorometric analysis of monocyte count in blood
Changes in basophil count in blood
Cytofluorometric analysis of baseophil count in blood
Changes in eosinophil count in blood
Cytofluorometric analysis of eosinophil count in blood
Changes in T-helper cell count in blood
Cytofluorometric analysis of T-helper cell count in blood
Changes in T cytotoxic cell count in blood
Cytofluorometric analysis of T cytotoxic cell count in blood
Changes in natural killer-T (NK-T) cell count in blood
Cytofluorometric analysis of NK-T cell count in blood
Changes in 62L macrophage count in blood
Cytofluorometric analysis of 62L macrophage count in blood
Changes in B lympho cell count in blood
Cytofluorometric analysis of B lympho cell count in blood
Changes in natural killer (NK) cell count in blood
Cytofluorometric analysis of natural killer cell count in blood
Changes in macrophage count in blood
Cytofluorometric analysis of macrophage count in blood
Changes in HLA+/Macr+ macrophage count in blood
Cytofluorometric analysis of HLA+/Macr+ count in blood
Changes in 11B+ macrophage count in blood
Cytofluorometric analysis of 11B+ macrophage count in blood

Secondary Outcome Measures

Changes in muscle performance
Assessment of maximal knee extensor eccentric peak torque on an isokinetic dynamometer at 60o/s.
Changes in delayed onset of muscle soreness
Assessment of the delayed onset of muscle soreness by palpation of the vastus lateralis and rectus femoris following a squat motion
Maximal aerobic capacity
Assessment of maximal oxygen consumption
Body composition
Measurement of body composition by Dual Emission X-ray Absorptiometry (DXA)
Changes in dietary intake profile
Assessment of dietary intake with emphasis on antioxidant element intake

Full Information

First Posted
October 4, 2016
Last Updated
October 7, 2016
Sponsor
National and Kapodistrian University of Athens
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1. Study Identification

Unique Protocol Identification Number
NCT02930031
Brief Title
Redox Status and Immune Function
Official Title
Evidence of a Redox-dependent Regulation of Immune Responses to Exercise-Induced Inflammation
Study Type
Interventional

2. Study Status

Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
January 2015 (undefined)
Primary Completion Date
February 2016 (Actual)
Study Completion Date
March 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National and Kapodistrian University of Athens

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
In this investigation the investigators utilized N-acetylcysteine (NAC) supplementation to enhance reduced glutathione (GSH) stores during an 8-day recovery period from a strenuous eccentric exercise protocol in order to test the hypotheses: i) redox status perturbations in skeletal muscle are pivotal for the immune responses and ii) antioxidant supplementation may alter immune cell responses following exercise-induced muscle microtrauma.
Detailed Description
The major thiol-disulfide couple of GSH and oxidized glutathione (GSSG) is a crucial regulator of the main transcriptional pathways regulating aseptic inflammation and recovery of skeletal muscle following aseptic injury. Antioxidant supplementation may hamper exercise-induced inflammatory responses. The objective was to examine how thiol-based antioxidant supplementation affects immune mobilization following exercise-induced skeletal muscle microtrauma. In a two-trial, double-blind, crossover, repeated measures design, 10 young men received either placebo or NAC (20 mg/kg/day) immediately after a muscle-damaging exercise protocol (300 eccentric contractions) and for eight consecutive days. Blood sampling and performance assessment were performed pre-exercise, 2h post-exercise and daily for 8 consecutive days.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Skeletal Muscle Damage, Aseptic Inflammation, Skeletal Muscle Function
Keywords
muscle injury, exercise, redox status, immune cells

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
n-acetylcysteine
Arm Type
Experimental
Arm Description
orally in three daily dosages, at 20 mg/kg/day, daily for eight days after exercise
Arm Title
Placebo
Arm Type
Active Comparator
Arm Description
orally in three daily dosages, content: 500 mL drink that contained water (375 mL), sugar-free cordial (125 ml), and 2 g of low-calorie glucose/dextrose powder
Intervention Type
Dietary Supplement
Intervention Name(s)
n-acetylcysteine
Other Intervention Name(s)
NAC
Intervention Description
20 mg//kg/day, orally, daily for eight days following exercise
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
500 mL orally, daily for eight days following exercise
Primary Outcome Measure Information:
Title
Changes in protein carbonyls in red blood cells
Description
Concentration of protein carbonyls
Time Frame
Pre-exercise, 2 hours post-exercise, daily for 8 consecutive days post-exercise
Title
Changes in thiobarbituric acid reactive substances in red blood cells
Description
Thiobarbituric acid reactive substances concentration in red blood cells
Time Frame
Pre-exercise, 2 hours post-exercise, daily for 8 consecutive days post-exercise
Title
Changes in total antioxidant capacity in serum
Time Frame
Pre-exercise, 2 hours post-exercise, daily for 8 consecutive days post-exercise
Title
Changes in reduced glutathione in blood
Description
Concentration of reduced glutathione in red blood cells
Time Frame
Pre-exercise, 2 hours post-exercise, daily for 8 consecutive days post-exercise
Title
Changes in oxidized glutathione in blood
Description
Concentration of oxidized glutathione in red blood cells
Time Frame
Pre-exercise, 2 hours post-exercise, daily for 8 consecutive days post-exercise
Title
Changes in catalase activity in red blood cells
Time Frame
Pre-exercise, 2 hours post-exercise, daily for 8 consecutive days post-exercise
Title
Changes in creatine kinase activity in serum
Time Frame
Pre-exercise, 2 hours post-exercise, daily for 8 consecutive days post-exercise
Title
Changes in high sensitivity C-reactive protein in serum
Time Frame
Pre-exercise, 2 hours post-exercise, 1 day post-exercise, 2 days post-exercise, 3 days post-exercise
Title
Changes in white blood cell count in blood
Time Frame
Pre-exercise, 2 hours post-exercise, daily for 8 consecutive days post-exercise
Title
Changes in adhesion molecule concentration in blood
Description
Measurement of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular cell adhesion molecule-1 (sICAM-1) concentrations in plasma
Time Frame
Pre-exercise, 2 hours post-exercise, 1 day post-exercise, 2 days post-exercise, 3 days post-exercise
Title
Changes in cytokine concentration in serum
Description
Measurement of interleukin-1β (IL-1β) and interleukin-6 (IL-6)
Time Frame
Pre-exercise, 2 hours post-exercise, 1 day post-exercise, 2 days post-exercise, 3 days post-exercise, 8 days post-exercise
Title
Changes in neutrophil count in blood
Description
Cytofluorometric analysis of neutrophil count in blood
Time Frame
Pre-exercise, 2 hours post-exercise, daily for 8 consecutive days post-exercise
Title
Changes in lymphocyte count in blood
Description
Cytofluorometric analysis of lymphocyte count in blood
Time Frame
Pre-exercise, 2 hours post-exercise, daily for 8 consecutive days post-exercise
Title
Changes in monocyte count in blood
Description
Cytofluorometric analysis of monocyte count in blood
Time Frame
Pre-exercise, 2 hours post-exercise, daily for 8 consecutive days post-exercise
Title
Changes in basophil count in blood
Description
Cytofluorometric analysis of baseophil count in blood
Time Frame
Pre-exercise, 2 hours post-exercise, daily for 8 consecutive days post-exercise
Title
Changes in eosinophil count in blood
Description
Cytofluorometric analysis of eosinophil count in blood
Time Frame
Pre-exercise, 2 hours post-exercise, daily for 8 consecutive days post-exercise
Title
Changes in T-helper cell count in blood
Description
Cytofluorometric analysis of T-helper cell count in blood
Time Frame
Pre-exercise, 2 hours post-exercise, daily for 8 consecutive days post-exercise
Title
Changes in T cytotoxic cell count in blood
Description
Cytofluorometric analysis of T cytotoxic cell count in blood
Time Frame
Pre-exercise, 2 hours post-exercise, daily for 8 consecutive days post-exercise
Title
Changes in natural killer-T (NK-T) cell count in blood
Description
Cytofluorometric analysis of NK-T cell count in blood
Time Frame
Pre-exercise, 2 hours post-exercise, daily for 8 consecutive days post-exercise
Title
Changes in 62L macrophage count in blood
Description
Cytofluorometric analysis of 62L macrophage count in blood
Time Frame
Pre-exercise, 2 hours post-exercise, daily for 8 consecutive days post-exercise
Title
Changes in B lympho cell count in blood
Description
Cytofluorometric analysis of B lympho cell count in blood
Time Frame
Pre-exercise, 2 hours post-exercise, daily for 8 consecutive days post-exercise
Title
Changes in natural killer (NK) cell count in blood
Description
Cytofluorometric analysis of natural killer cell count in blood
Time Frame
Pre-exercise, 2 hours post-exercise, daily for 8 consecutive days post-exercise
Title
Changes in macrophage count in blood
Description
Cytofluorometric analysis of macrophage count in blood
Time Frame
Pre-exercise, 2 hours post-exercise, daily for 8 consecutive days post-exercise
Title
Changes in HLA+/Macr+ macrophage count in blood
Description
Cytofluorometric analysis of HLA+/Macr+ count in blood
Time Frame
Pre-exercise, 2 hours post-exercise, daily for 8 consecutive days post-exercise
Title
Changes in 11B+ macrophage count in blood
Description
Cytofluorometric analysis of 11B+ macrophage count in blood
Time Frame
Pre-exercise, 2 hours post-exercise, daily for 8 consecutive days post-exercise
Secondary Outcome Measure Information:
Title
Changes in muscle performance
Description
Assessment of maximal knee extensor eccentric peak torque on an isokinetic dynamometer at 60o/s.
Time Frame
Pre-exercise, 2 hours post-exercise, daily for 8 consecutive days post-exercise
Title
Changes in delayed onset of muscle soreness
Description
Assessment of the delayed onset of muscle soreness by palpation of the vastus lateralis and rectus femoris following a squat motion
Time Frame
Pre-exercise, 2 hours post-exercise, daily for 8 consecutive days post-exercise
Title
Maximal aerobic capacity
Description
Assessment of maximal oxygen consumption
Time Frame
One day before exercise
Title
Body composition
Description
Measurement of body composition by Dual Emission X-ray Absorptiometry (DXA)
Time Frame
One day before exercise
Title
Changes in dietary intake profile
Description
Assessment of dietary intake with emphasis on antioxidant element intake
Time Frame
One day before exercise and daily for 8 consecutive days post-exercise

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Recreationally trained (VO2max > 45 ml/kg/min) Engaged in regular exercise for ≥3 times/week for > 12 months non-smokers Abstain from exercise during the course of the two trials No consumption of performance-enhancing substances, antioxidants, caffeine, alcohol and/or medications during the study. Exclusion Criteria: NAC intolerance Recent musculoskeletal injuries of the lower limbs Febrile illness History of muscle lesion.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Asimina Mitrakou, Associate Prof.
Organizational Affiliation
Department of Diabetes and Metabolism Unit of the Department of Clinical Therapeutics, National and Kapodistrian University of Athens
Official's Role
Study Director
Facility Information:
Facility Name
University of Athens, Medical School, Department of Clinical Therapeutics
City
Athens
ZIP/Postal Code
11527
Country
Greece

12. IPD Sharing Statement

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Redox Status and Immune Function

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