Glutathione Metabolism AnemiasPhase 2NCT03121222
The Effects of N-acetylcysteine on Performance and Redox Homeostasis
A Phase 2 study testing N-acetylcysteine and Lactose in people with Glutathione Metabolism Anemias, run by Aristotle University Of Thessaloniki at 3 sites in 2 countries.
Trial summary
The main objective of the present study was to investigate whether N-acetylcysteine supplementation in individuals with low glutathione levels would confer ergogenic effects by replenishing glutathione levels and by reducing oxidative stress. Read more about this study
- Who is it for?
- Ages 18 to 29 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Glutathione Metabolism Anemias
- What is being tested?
- N-acetylcysteine and Lactose
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 1 Nov 2015to 12 Sep 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 29 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male subjects who participated recreationally in physical activities less than 3 times per week.
Who cannot join
- Subjects were excluded from the study, if they reported any musculoskeletal injury that would limit their ability to perform the exercise sessions. Participants were asked to recall whether they had participated in regular resistance or aerobic training or in unaccustomed exercise during the period before the study entry. Individuals who reported such activities were precluded from the study. Smoking and consumption of antioxidant supplements the days prior to the study were additional exclusion criteria.
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Greece2 sites
National and Kapodistrian University of Athens
Athens, 17237
Aristotle University of Thessaloniki
Thessaloniki, 54124
About this study
Official title: N-acetylcysteine Supplementation in Individuals With Low Glutathione Levels: the Effects on Physical Performance and Redox Homeostasis
The main objective of the present study was to investigate whether N-acetylcysteine supplementation in individuals with low glutathione levels would confer ergogenic effects by replenishing glutathione levels and by reducing oxidative stress. Towards this aim, investigators sought to exploit the large inter-individual variability in redox biomarker levels. More specifically, investigators screened 100 male participants for glutathione baseline levels in blood and formed three stratified groups according to this value (i.e., low, moderate and high; 12 individuals per group). After by-passing the regression to the mean artefact by performing a second glutathione measurement in the three aforementioned groups, investigators assessed both aerobic and anaerobic physical performance in order to acquire a more comprehensive view about the ergogenic effectiveness of the antioxidant treatment. This was accomplished by implementing three different whole-body physical performance tests (i.e., VO2max test, time trial and Wingate), as opposed to most in vivo studies that either applied isolated body-part exercise tests (e.g., by isokinetic dynamometry) or performed a single exercise test (e.g., time-to-fatigue test). It was hypothesised, that data of the present investigation will bridge the chasm between the scientific (i.e., chronic antioxidant supplementation blunts exercise performance and adaptations) and the community-based (i.e., free radicals should anyway be counteracted by "protective" exogenous antioxidants) truths about the role of antioxidants as ergogenic aids. It was also hypothesised that the results will show that low glutathione levels are linked to decreased aerobic and anaerobic physical performance accompanied by increased levels of oxidative stress and that N-acetylcysteine supplementation will restore both performance and redox homeostasis. Based on the findings of the present investigation, the widespread routine practice of consuming antioxidants during exercise training could be changed and the consumption of antioxidants would be restricted only for those who are deficient in glutathione.
- Conditions
- Glutathione Metabolism Anemias
- Being tested
- N-acetylcysteine, Lactose
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetylcysteineDrug
The antioxidant group received orally two N-acetylcysteine tablets (each tablet contained 600 mg of NAC; Lamberts Health Care Ltd, Kent, United Kingdom). The participants were instructed to receive the capsules every twelve hours in order to achieve high concentration of N-acetylcysteine throughout the 24 h. Each individual received the capsules pre-packed in daily doses labeled with the day of consumption. The supplementation period was 30-day for N-acetylcysteine.
LactoseDrug
The placebo group received orally two lactose tablets per day. The participants were instructed to receive the capsules every twelve hours. Each individual received the capsules pre-packed in daily doses labeled with the day of consumption. The supplementation period was 30-day for placebo.
| Study group | Role | What they receive |
|---|---|---|
| Lactose | Placebo comparator | The placebo group received orally two lactose tablets per day for 30 days. Each individual received the capsules pre-packed in daily doses labeled with the day of consumption. Receives: Drug: Lactose |
| N-acetylcysteine | Experimental | The antioxidant group received orally two N-acetylcysteine tablets (each tablet contained 600 mg of NAC; Lamberts Health Care Ltd, Kent, United Kingdom). The participants were instructed to receive the capsules every twelve hours in order to achieve high concentration of N-acetylcysteine throughout the 24 h. Each individual received the capsules pre-packed in daily doses labeled with the day of consumption. Receives: Drug: N-acetylcysteine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurement of maximal oxygen consumption (ml/kg/min)
Maximal oxygen consumption was assessed (using incremental cycling test to volitional exhaustion) on cycle ergometers (Monark, Vansbro, Sweden). Briefly, after a 5-min warm-up period at 100W, workload increased by 50W every 2.5 minutes until heart rate reached 160 bpm. Then, workload increased by 25W every 2.5 minutes until exhaustion. Respiratory gas variables were measured using a metabolic cart (Quark b2, Cosmed, Italy), which was calibrated before each test using standard gases of known concentration.
Maximal oxygen consumption along with time trial and wingate test were used for assessing both aerobic and anaerobic physical performance in order to acquire a more comprehensive view about the ergogenic effectiveness of the antioxidant treatment.
Measured: 64 days
Secondary outcomes (1)
Measurement of glutathione levels (μmol/g Hb)
Erythrocyte GSH was determined spectrophotometrically. 20 μL of erythrocyte lysate treated with 5% TCA mixed with 660 μL of67 mMsodium potassium phosphate (pH 8.0) and 330 μL of 1mM 5,5- dithiobis-2 nitrobenzoate. The samples were incubated in the dark at room temperature for 45 min, and the absorbance was read at 412 nm.
The measurement of glutathione was used for assessing the efficacy of NAC supplementation to restore glutathione levels in the low-glutathione group as well as the effects of NAC supplementation in the medium and high glutathione groups.
Measured: 64 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2017
- Study start1 Nov 2015
- Primary completion15 Feb 2016
- Study completion12 Sep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Glutathione Metabolism AnemiasStudies of the same condition, open and under way.
- More trials run by Aristotle University Of ThessalonikiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aristotle University Of Thessaloniki
- Sponsor type
- University, hospital or other
- Collaborators
- National and Kapodistrian University of Athens, European University Cyprus
- Responsible party
- Principal investigator, Vassilis Paschalis, National and Kapodistrian University of Athens
- Investigators
- Michalis Nikolaidis, PhD, Study director, Aristotle University Of Thessaloniki
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03121222
- Sponsor's protocol ID
- 83022/2015
- Status last verified
- Apr 2017
- First submitted
- 6 Apr 2017
- Last updated
- 21 Apr 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Margaritelis NV, Theodorou AA, Paschalis V, Veskoukis AS, Dipla K, Zafeiridis A, Panayiotou G, Vrabas IS, Kyparos A, Nikolaidis MG. Experimental verification of regression to the mean in redox biology: differential responses to exercise. Free Radic Res. 2016;50(11):1237-1244. doi: 10.1080/10715762.2016.1233330. Epub 2016 Oct 25.
PubMed 27596985Jeukendrup A, Saris WH, Brouns F, Kester AD. A new validated endurance performance test. Med Sci Sports Exerc. 1996 Feb;28(2):266-70. doi: 10.1097/00005768-199602000-00017.
PubMed 8775164Paschalis V, Theodorou AA, Kyparos A, Dipla K, Zafeiridis A, Panayiotou G, Vrabas IS, Nikolaidis MG. Low vitamin C values are linked with decreased physical performance and increased oxidative stress: reversal by vitamin C supplementation. Eur J Nutr. 2016 Feb;55(1):45-53. doi: 10.1007/s00394-014-0821-x. Epub 2014 Dec 20.
PubMed 25526969Nikolaidis MG, Kyparos A, Spanou C, Paschalis V, Theodorou AA, Panayiotou G, Grivas GV, Zafeiridis A, Dipla K, Vrabas IS. Aging is not a barrier to muscle and redox adaptations: applying the repeated eccentric exercise model. Exp Gerontol. 2013 Aug;48(8):734-43. doi: 10.1016/j.exger.2013.04.009. Epub 2013 Apr 28.
PubMed 23628501
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- N-acetylcysteine Supplementation in Individuals With Low Glutathione Levels: the Effects on Physical Performance and Redox Homeostasis
- ClinicalTrials.gov ID
- NCT03121222
- Acronym / sponsor ID
- 83022/2015
- Conditions
- Glutathione Metabolism Anemias
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Aristotle University Of ThessalonikiUniversity, hospital or other
- Collaborators
- National and Kapodistrian University of Athens, European University Cyprus
- Study start
- 1 Nov 2015 (actual)
- Primary completion
- 15 Feb 2016 (actual)
- Study completion
- 12 Sep 2016 (actual)
- First posted
- 20 Apr 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main objective of the present study was to investigate whether N-acetylcysteine supplementation in individuals with low glutathione levels would confer ergogenic effects by replenishing glutathione levels and by reducing oxidative stress. Towards this aim, investigators sought to exploit the large inter-individual variability in redox biomarker levels. More specifically, investigators screened 100 male participants for glutathione baseline levels in blood and formed three stratified groups according to this value (i.e., low, moderate and high; 12 individuals per group). After by-passing the regression to the mean artefact by performing a second glutathione measurement in the three aforementioned groups, investigators assessed both aerobic and anaerobic physical performance in order to acquire a more comprehensive view about the ergogenic effectiveness of the antioxidant treatment. This was accomplished by implementing three different whole-body physical performance tests (i.e., VO2max test, time trial and Wingate), as opposed to most in vivo studies that either applied isolated body-part exercise tests (e.g., by isokinetic dynamometry) or performed a single exercise test (e.g., time-to-fatigue test). It was hypothesised, that data of the present investigation will bridge the chasm between the scientific (i.e., chronic antioxidant supplementation blunts exercise performance and adaptations) and the community-based (i.e., free radicals should anyway be counteracted by "protective" exogenous antioxidants) truths about the role of antioxidants as ergogenic aids. It was also hypothesised that the results will show that low glutathione levels are linked to decreased aerobic and anaerobic physical performance accompanied by increased levels of oxidative stress and that N-acetylcysteine supplementation will restore both performance and redox homeostasis. Based on the findings of the present investigation, the widespread routine practice of consuming antioxidants during exercise training could be changed and the consumption of antioxidants would be restricted only for those who are deficient in glutathione.
Study design
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lactose | Placebo comparator | Drug: LactoseThe placebo group received orally two lactose tablets per day for 30 days. Each individual received the capsules pre-packed in daily doses labeled with the day of consumption. |
| N-acetylcysteine | Experimental | Drug: N-acetylcysteineThe antioxidant group received orally two N-acetylcysteine tablets (each tablet contained 600 mg of NAC; Lamberts Health Care Ltd, Kent, United Kingdom). The participants were instructed to receive the capsules every twelve hours in order to achieve high concentration of N-acetylcysteine throughout the 24 h. Each individual received the capsules pre-packed in daily doses labeled with the day of consumption. |
Who may qualify
- Ages
- 18 to 29 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Healthy male subjects who participated recreationally in physical activities less than 3 times per week.
Key exclusion criteria (1 listed)
- Subjects were excluded from the study, if they reported any musculoskeletal injury that would limit their ability to perform the exercise sessions. Participants were asked to recall whether they had participated in regular resistance or aerobic training or in unaccustomed exercise during the period before the study entry. Individuals who reported such activities were precluded from the study. Smoking and consumption of antioxidant supplements the days prior to the study were additional exclusion criteria.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-acetylcysteineThe antioxidant group received orally two N-acetylcysteine tablets (each tablet contained 600 mg of NAC; Lamberts Health Care Ltd, Kent, United Kingdom). The participants were instructed to receive the capsules every twelve hours in order to achieve high concentration of N-acetylcysteine throughout the 24 h. Each individual received the capsules pre-packed in daily doses labeled with the day of consumption. The supplementation period was 30-day for N-acetylcysteine. | Drug | N-acetylcysteine |
| LactoseThe placebo group received orally two lactose tablets per day. The participants were instructed to receive the capsules every twelve hours. Each individual received the capsules pre-packed in daily doses labeled with the day of consumption. The supplementation period was 30-day for placebo. | Drug | Lactose |
Primary outcome
Measurement of maximal oxygen consumption (ml/kg/min)
Time frame: 64 days
Maximal oxygen consumption was assessed (using incremental cycling test to volitional exhaustion) on cycle ergometers (Monark, Vansbro, Sweden). Briefly, after a 5-min warm-up period at 100W, workload increased by 50W every 2.5 minutes until heart rate reached 160 bpm. Then, workload increased by 25W every 2.5 minutes until exhaustion. Respiratory gas variables were measured using a metabolic cart (Quark b2, Cosmed, Italy), which was calibrated before each test using standard gases of known concentration. Maximal oxygen consumption along with time trial and wingate test were used for assessing both aerobic and anaerobic physical performance in order to acquire a more comprehensive view about the ergogenic effectiveness of the antioxidant treatment.
1 secondary outcome
Measurement of glutathione levels (μmol/g Hb)
Time frame: 64 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2017.
- Background: PubMed 27596985Margaritelis NV, Theodorou AA, Paschalis V, Veskoukis AS, Dipla K, Zafeiridis A, Panayiotou G, Vrabas IS, Kyparos A, Nikolaidis MG. Experimental verification of regression to the mean in redox biology: differential responses to exercise. Free Radic Res. 2016;50(11):1237-1244. doi: 10.1080/10715762.2016.1233330. Epub 2016 Oct 25.
- Background: PubMed 8775164Jeukendrup A, Saris WH, Brouns F, Kester AD. A new validated endurance performance test. Med Sci Sports Exerc. 1996 Feb;28(2):266-70. doi: 10.1097/00005768-199602000-00017.
- Background: PubMed 25526969Paschalis V, Theodorou AA, Kyparos A, Dipla K, Zafeiridis A, Panayiotou G, Vrabas IS, Nikolaidis MG. Low vitamin C values are linked with decreased physical performance and increased oxidative stress: reversal by vitamin C supplementation. Eur J Nutr. 2016 Feb;55(1):45-53. doi: 10.1007/s00394-014-0821-x. Epub 2014 Dec 20.
- Background: PubMed 23628501Nikolaidis MG, Kyparos A, Spanou C, Paschalis V, Theodorou AA, Panayiotou G, Grivas GV, Zafeiridis A, Dipla K, Vrabas IS. Aging is not a barrier to muscle and redox adaptations: applying the repeated eccentric exercise model. Exp Gerontol. 2013 Aug;48(8):734-43. doi: 10.1016/j.exger.2013.04.009. Epub 2013 Apr 28.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michalis Nikolaidis, PhD study director
Aristotle University Of Thessaloniki
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing N-acetylcysteine and Lactose in people with Glutathione Metabolism Anemias, run by Aristotle University Of Thessaloniki at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Greece, Cyprus. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measurement of maximal oxygen consumption (ml/kg/min) (time frame: 64 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03121222, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2017.