Redox Status and Exercise Training-induced Adaptations

NCT07196852 | Recruiting

• 1 other identifier: UTH-2568_2.4.2025
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Excess fat accumulation is a key feature of overweight and obesity that is mainly driven by nutrient overload and insufficient physical activity. White adipose tissue displays lipid overload and hypertrophy accompanied by macrophages infiltration, hypoxia, inflammation and excess production of reactive oxygen species (ROS). An inflammatory response and ROS production are also evident in other metabolism regulating tissues and organs such as skeletal muscle, liver, pancreas and hypothalamus, contributing to a chronic inflammatory state, redox status disturbances and metabolic complications. There is overwhelming evidence showing that adults with overweight/obesity exhibit lower glutathione (GSH) levels in blood erythrocytes, skeletal muscle cells and subcutaneous and visceral adipose tissue cells. GSH, a tripeptide consisting of the amino acids glutamate, cysteine and glycine, is the most abundant thiol-containing antioxidant in the human body and has been, recently, characterized as a novel therapeutic target for the treatment of numerous chronic diseases, due to its potent intracellular redox buffering capacity. Interestingly, lower GSH levels have been associated with diet-induced weight loss resistance, while enhancement of GSH levels through N-acetylcysteine (NAC) supplementation reduces markers of oxidative stress, inflammation, insulin resistance, hypertension, endothelia dysfunction and improves vitamin D metabolism. NAC is a thiol donor that elicits antioxidant effects by (i) directly scavenging ROS and (ii) providing reduced cysteine through deacetylation, which supports the biosynthesis of endogenous GSH via the activity of γ-glutamylcysteine synthase. The aim of this study is to investigate whether NAC supplementation can enhance the exercise training-induced improvements on physical fitness and metabolic health in adult men and women with overweight/obesity.

Conditions

Overweight (BMI > 25); Obesity

Keywords

overweight; obesity; N-acetylcysteine; high-intensity interval training

Outcome Measures

Primary Outcomes (33)

• Change in body weight (kg)

  At baseline, 6 weeks and 12 weeks

• Change in waist circumference

  At baseline, 6 weeks and 12 weeks

• Change in hip circumference

  At baseline, 6 weeks and 12 weeks

• Change in fat mass (kg)

  Fat mass will be assessed through dual energy X-ray absorptiometry (DXA)

  At baseline, 6 weeks and 12 weeks

• Change in body fat percent (%)

  Body fat percent will be assessed through dual energy X-ray absorptiometry (DXA)

  At baseline, 6 weeks and 12 weeks

• Change in fat free mass (kg)

  Fat free mass will be assessed through dual energy X-ray absorptiometry (DXA)

  At baseline, 6 weeks and 12 weeks

• Change in lean body mass (kg)

  Lean body mass will be assessed through dual energy X-ray absorptiometry (DXA)

  At baseline, 6 weeks and 12 weeks

• Change in liver fat infiltration

  Liver fat infiltration will be assessed through ultrasound elastography

  At baseline and 12 weeks

• Change in cardiorespiratory fitness

  Maximal oxygen consumption (VO2max) will be estimated during a single stage treadmill test (Ebbeling single stage test)

  At baseline, 6 weeks and 12 weeks

• Change in lower body muscle strength

  Maximal concentric peak torque will be assessed on an isokinetic dynamometer

  At baseline, 6 weeks and 12 weeks

• Change in upper body muscle strength

  Upper body muscle strength will be assessed through the abdominal strength test and the push-up test

  At baseline, 6 weeks and 12 weeks

• Change in reduced glutathione (GSH) concentration

  GSH concentration will be determined in blood erythrocytes and peripheral blood mononuclear cells

  At baseline, 6 weeks and 12 weeks

• Change in oxidized glutathione (GSSG) concentration

  GSSG concentration will be determined in blood erythrocytes and peripheral blood mononuclear cells

  At baseline, 6 weeks and 12 weeks

• Change in glutathione peroxidase (GPx) activity

  GPx activity will be determined in blood erythrocytes and peripheral blood mononuclear cells

  At baseline, 6 weeks and 12 weeks

• Change in glutathione reductase (GR) activity

  GR activity will be determined in blood erythrocytes and peripheral blood mononuclear cells

  At baseline, 6 weeks and 12 weeks

• Change in catalase activity

  Catalase activity will be determined in blood erythrocytes and peripheral blood mononuclear cells

  At baseline, 6 weeks and 12 weeks

• Change in superoxide dismutase (SOD) activity

  SOD activity will be determined in blood erythrocytes and peripheral blood mononuclear cells

  At baseline, 6 weeks and 12 weeks

• Change in malondialdehyde concentration

  Malondialdehyde concentration will be determined in peripheral blood mononuclear cells

  At baseline, 6 weeks and 12 weeks

• Change in C-reactive protein (CRP) concentration

  At baseline, 6 weeks and 12 weeks

• Change in TNF-α concentration

  TNF-α concentration will be determined in blood and peripheral blood mononuclear cells

  At baseline, 6 weeks and 12 weeks

• Change in interleukin-6 (IL-6) concentration

  IL-6 concentration will be determined in blood and peripheral blood mononuclear cells

  At baseline, 6 weeks and 12 weeks

• Change in HDL cholesterol concentration

  HDL cholesterol concentration will be determined in blood

  At baseline, 6 weeks and 12 weeks

• Change in LDL cholesterol concentration

  LDL cholesterol concentration will be determined in blood

  At baseline, 6 weeks and 12 weeks

• Change in total cholesterol concentration

  Total cholesterol concentration will be determined in blood

  At baseline, 6 weeks and 12 weeks

• Change in triglycerides concentration

  Triglycerides concentration will be determined in blood

  At baseline, 6 weeks and 12 weeks

• Change in serum glutamic-oxaloacetic transaminase (SGOT/AST) concentration

  SGOT concentration will be determined in blood

  At baseline, 6 weeks and 12 weeks

• Alanine Aminotransferase (SGPT/ALT) concentration

  SGPT concentration will be determined in blood

  At baseline, 6 weeks and 12 weeks

• Change in Gamma-glutamyl transpeptidase (γ-GT) concentration

  γ-GT concentration will be determined in blood

  At baseline, 6 weeks and 12 weeks

• Change in fetuin-A concentration

  Fetuin-A concentration will be determined in blood

  At baseline, 6 weeks and 12 weeks

• Change in alkaline phosphatase (ALP) concentration

  ALP concentration will be determined in blood

  At baseline, 6 weeks and 12 weeks

• Change in glucose concentration

  Glucose concentration will be determined in blood

  At baseline, 6 weeks and 12 weeks

• Change in glycated hemoglobin (HbA1c) concentration

  HbA1c concentration will be determined in blood

  At baseline, 6 weeks and 12 weeks

• Change in insulin concentration

  Insulin concentration will be determined in blood

  At baseline, 6 weeks and 12 weeks

Secondary Outcomes (3)

• Change in dietary intake

  At baseline, 6 weeks and 12 weeks

• Change in total number of steps

  At baseline, 6 weeks and 12 weeks

• Change in time spent in moderate-to-vigorous physical activity

  At baseline, 6 weeks and 12 weeks

Study Arms (2)

N-acetylcysteine

EXPERIMENTAL

Oral N-acetylcysteine supplementation for 12 weeks (2 x 600 mg capsules/day)

Dietary Supplement: N Acetyl L Cysteine

Placebo

PLACEBO COMPARATOR

Oral placebo supplementation for 12 weeks (2 placebo capsules/day)

Dietary Supplement: Placebo

Interventions

N Acetyl L Cysteine DIETARY_SUPPLEMENT

Participants will participate in 3 multicomponent high-intensity interval training (m-HIIT) sessions per week over a 12-week period while receiving daily 1200 mg N-acetylcysteine (2 pills x 600 mg/day ).

N-acetylcysteine

Placebo DIETARY_SUPPLEMENT

Participants will participate in 3 multicomponent high-intensity interval training (m-HIIT) sessions per week over a 12-week period while receiving daily 2 placebo pills/day.

Placebo

Eligibility Criteria

• Age: 30 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• BMI 25-35 kg/m2
• Free of musculoskeletal injuries
• Free of chronic non-communicable diseases
• Do not receive any drug therapy
• Do not receive dietary supplements
• Normal menstrual cycle (for females)
• Non smokers

You may not qualify if:

• NAC intolerance
• Bleeding disorders
• Kidney disease
• Asthma
• Usage of blood thinners and/or angina medication

Sponsors & Collaborators

• University of Thessaly: lead

Study Sites (1)

Department of Physical Education and Sport Science, University of Thessaly

Trikala, Karies, 42100, Greece

RECRUITING

MeSH Terms

Conditions

Overweight; Obesity

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Anastasia Rosvoglou, PhDc

  University of Thessaly, Department of Physical Education and Sport Science

  PRINCIPAL INVESTIGATOR

• Dimitrios Draganidis, PhD

  University of Thessaly, Department of Physical Education and Sport Science

  STUDY DIRECTOR

Central Study Contacts

Dimitrios Draganidis, PhD

CONTACT

+30 2431047078; ddraganidis@uth.gr

Ioannis G. Fatouros, PhD

CONTACT

+30 2431047047; ifatouros@uth.gr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Randomized clinical trial with repeated measures

Study Record Dates

• First Submitted: September 19, 2025
• First Posted: September 29, 2025
• Study Start: September 22, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: December 16, 2025

Record last verified: 2025-12

Locations

GR (1)